Ariz Law

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CHAPTER 1
OVERVIEW OF
ARIZONA PHARMACY LAW
(2 CONTACT HOURS - Required)
By Katie Ingersoll, RPh, Pharm D and staff pharmacist
for national chain.
Author Disclosure: Katie Ingersoll and Elite
Professional Education do not have any actual or
potential conficts of interest in relation to this lesson.
Universal Activity Number (UAN):
0761-9999-13-275-H03-T
Activity Type: Knowledge-based
Initial Release Date: July 30, 2013
Expiration Date: July 30, 2015
Target Audience: Pharmacy Technicians in a
community-based setting.
To Obtain Credit: A minimum test score of 70 percent
is needed to obtain a credit. Please submit your answers
either by mail, fax, or online at www.elitecme.com.
Questions regarding statements of credit and other
customer service issues should be directed to 1-888-
666-9053. This lesson is $10.00.
Educational Review Systems is accredited
by the Accreditation Council of Pharmacy
Education (ACPE) as a provider of
continuing pharmaceutical education. This
program is approved for 2 hours (0.2
CEUs) of continuing pharmacy education credit. Proof
of participation will be posted to your NABP CPE
profle within 4 to 6 weeks to participants who have
successfully completed the post-test. Participants must
participate in the entire presentation and complete the
course evaluation to receive continuing pharmacy
education credit.
Learning objectives
! Describe the members of the Arizona Board
of Pharmacy, including how many there are,
their qualifcations, and how they become
eligible for board appointment.
! List the responsibilities of the Arizona Board
of Pharmacy.
! Describe pharmacy setup and security
requirements.
! List the types of prescribers who may
prescribe medications in the state of Arizona
and any restrictions on their prescribing
authority.
! Discuss requirements for flling prescriptions
in Arizona, including requirements for
flling prescriptions written by Mexican and
Canadian prescribers.
! Explain generic substitution requirements
in Arizona and when it is appropriate to
dispense a generic medication.
! Describe the valid time frame for dispensing
reflls of medications in Arizona, including
reflls and time frame restrictions on
controlled substances.
! Discuss the regulations on the dispensing of
controlled substances without a prescription,
including quantity limits and record keeping.
! Describe the requirements for the sale of
pseudoephedrine, including quantity limits
and record keeping.
! Explain patient counseling requirements and
who can counsel a patient.
pharmacist actively working at a licensed
hospital. Pharmacists can serve fve-year terms
on the Board of Pharmacy.
The pharmacy technician member of the Board
of Pharmacy must have at least fve years of
experience actively working in a pharmacy, and
must have been a resident of Arizona for the fve-
year period preceding appointment. Pharmacy
technicians may serve a fve-year term on the
board. The two public members also are required
to have residency status in Arizona for the fve
years preceding their appointment, and may serve
a fve-year term unless they are removed by the
governor. All members of the Arizona Board of
Pharmacy are appointed by the governor.
The Board of Pharmacy must elect a president
and vice-president annually. The president must
be present at all board meetings; the vice-
president may act in place of the president if the
president is not present. The Board of Pharmacy
must hold at least four meetings per year and
provide an annual report to the governor,
including the names of all persons and facilities
licensed by the Board of Pharmacy.
The Board of Pharmacy is responsible for
developing and maintaining laws and rules
to protect the public on any issue related to
pharmacies, pharmacists, pharmacy technicians,
the storage, distribution or manufacture of
medications, and the practice of pharmacy. It is
also responsible for the enforcement of its rules
and laws.
To properly enforce pharmacy rules and laws,
the Board of Pharmacy or its designated
employees have the right to enter any pharmacy,
manufacturing plant, wholesaler, storage facility,
or vehicle used in the manufacture, storage, or
sale of prescription medications. Inspections can
be conducted at any time the facility in question
is open, and prior notice is not required.
The Board of Pharmacy is also responsible for
providing notice at least once every three months
of any changes to prescribing authority of any
prescriber licensed to practice in Arizona.
Pharmacy setup and security
Pharmacies in Arizona must have a dispensing,
compounding, and drug stocking area that is at
least 300 feet.
2
If the minimum pharmacy size
is used, no more than three personnel may work
at the same time. Each additional staff member
requires an additional 60 feet
2
of foor space. This
is to allow pharmacists adequate space to monitor
the activities of pharmacy personnel and ensure
effcient workfow.
Each employee working at the same time should
have at least 3 feet
2
of counter space, and it must
be at least 16 inches deep and 24 inches long to
be sure all of them have space to spread out their
work to minimize error potential.
Counter space should be contained by a barrier
at least 66 inches tall to prevent unauthorized
persons from seeing the pharmacy counter,
potentially violating a patients privacy. The foor
! Describe prescription transfer regulations and
what information must be recorded during a
prescription transfer.
! Explain the pharmacy record keeping
requirements under Arizona law.
! Describe the licensing requirements for
pharmacies and the types of permits that may
be issued by the Arizona Board of Pharmacy,
as well as renewal requirements.
! Discuss the licensing and continuing
education requirements for pharmacists.
! Discuss the responsibilities of pharmacy
interns and their licensing requirements.
! Discuss the responsibilities of pharmacy
technicians and their licensing and continuing
education requirements.
! Describe regulations on immunization by
pharmacists, including the certifcation
process and who can be immunized.
! List the vaccines that require a prescription to
be administered to an adult patient.
Introduction
State laws and regulations governing pharmacy
practice are extremely important in the day-to-
day work of a pharmacy associate. From the
license needed to work in the pharmacy to the
foor space necessary for each employee, laws
and regulations govern every aspect of daily
pharmacy operation. As a pharmacy employee, it
is imperative to maintain a working knowledge of
state pharmacy laws, and continue to learn about
new laws that have been passed as well.
All states have variations in their state pharmacy
laws that distinguish them from other states.
While state laws in Arizona are similar to others,
there are signifcant differences that must also
be reviewed. This course is designed to be an
overview of the pertinent state pharmacy laws
in Arizona for the pharmacist and pharmacy
technician.
Information included in this course was current as
of the time of writing. Remember that laws may
change, and be sure to consult the Arizona State
Law Book for a thorough explanation of each
law. This course is an overview of the pertinent
Arizona state laws, and may not be all-inclusive
see the law book for full details.
Arizona State Board of Pharmacy
The Arizona State Board of Pharmacy is the
governing body for pharmacy affairs in the state
of Arizona, and is also responsible for issuing
licenses to pharmacists, interns, technicians,
pharmacies, drug wholesalers, and drug
manufacturers.
The board consists of nine members: six
pharmacists, one pharmacy technician, and two
members of the public. The pharmacists who are
members of the Board of Pharmacy must have
at least 10 years of experience before they are
eligible for appointment, and at least fve years of
experience as a licensed pharmacist in Arizona.
Pharmacist members must have been a resident of
Arizona for the fve years preceding appointment.
There must be at least one actively practicing
community pharmacist, and at least one
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space along the dispensing and compounding
counter must be at least 36 inches wide.
New pharmacies must have a separate patient
counseling area to allow patients privacy during
consultation.
NOTE: Pharmacy size regulations must be
addressed and discussed with the Board of
Pharmacy when applying for a permit to operate
a pharmacy.
Controlled substances can be kept in a safe or
locked cabinet or distributed throughout the
stock of prescription medications; it is up to the
pharmacy to decide what best suits its needs to
maximize effciency and minimize theft.
The pharmacy must be surrounded from foor
to ceiling by a permanent barrier with secure
entry points. It should be designed in a way that
the pharmacist is the only person who can gain
entry to the area where prescription medications
and controlled substances are kept, and only
a licensed pharmacist may carry a key to the
pharmacy.
All prescription medications and medical devices
must be stored in a clean, organized space that
is well lit, well ventilated, dry, and maintains
adequate temperatures for medication storage.
A separate drug storage area outside of the
pharmacy may be used if necessary, but it must
be enclosed from foor to ceiling by a secure
barrier that only the pharmacist can access with
a key.
Who can prescribe medications in
Arizona?
1,3
In the state of Arizona, many different types
of practitioners can prescribe medications to
patients. Some of these prescribers have limits
to their prescription authority, such as treatment
limited to certain body parts or limits to the
prescription of controlled substances. It is very
important to be aware of the various types of
prescribers and their authority limits to ensure
prescriptions are flled within the limits of the
law.
Type of prescriber Prescription authority
Medical doctor Independent prescribing
authority, unlimited.
Doctor of
osteopathy
Independent prescribing
authority, unlimited.
Dentist Independent prescribing
authority limited to
scope of practice
prescribing authority is
limited to treatment of
mouth, teeth and gums.
Podiatrist Independent prescribing
scope of practice
prescribing authority
is limited to treatment
of feet; can prescribe
controlled substances
with board approval.
Veterinarian Independent prescribing
scope of practice
prescribing authority is
limited to treatment of
animals.
Physician assistant Can prescribe non-
controlled medications
without limits.
Controlled substances
can only be prescribed
with written consent of
a supervising physician,
and only up to a 30-
day supply may be
prescribed at once.
2
Registered nurse
practitioner
Can prescribe non-
controlled and controlled
medications with board
approval, independent
prescribing authority.
EMT/paramedic Does not have any
Chiropractor Does not have any
Naturopathic
doctor
Limited independent
prescribing authority
cannot prescribe
chemotherapy,
antipsychotics, or
IV medications. Can
prescribe controlled
substances, except
the only Schedule II
medication that may be
prescribed is morphine.
Schedule III-V
can be prescribed.
Optometrist Limited independent
Can prescribe non-
controlled medications
with board approval;
the only controlled
medications that may
be prescribed are
Schedule III analgesics.
Prescribing quantity
limitations may apply.
Pharmacist Can start, alter, or
discontinue medication
therapy under a
collaborative agreement
with a supervising
physician. May also
administer most
immunizations without a
prescription after earning
certifcation.
Prescription requirements in Arizona
Prescriptions flled in Arizona must meet the
following requirements:
Prescriptions must be written by a prescriber
with prescribing authority in Arizona as noted
in the chart in the previous section.
Handwritten prescriptions must include the
prescribers actual signature.
Prescription orders sent to the pharmacy
in electronic format must include the
prescribers electronic signature, and must
be printed or reduced to writing before flling
the prescription.
Written prescriptions that are printed from an
electronic database and given to the patient
may use the prescribers actual or electronic
signature. Printed prescriptions given to
a patient that only use the prescribers
electronic signature must be printed on
tamper-resistant paper.
Oral prescription orders may be called in to
the pharmacy if the pharmacist reduces the
prescription to writing immediately.
Reflls may be given if authorized by the
prescriber and if they are documented and
fled properly by the pharmacist.
Prescription orders may also be sent by the
prescribers offce via fax or electronic mail.
The patient may send prescription orders via
fax or email if the prescription hard copy is
presented to the pharmacy upon pickup of the
medication.
All written prescriptions flled for patients
using Arizona Medicaid or federal Medicare
services for payment must be printed on
tamper-resistant paper to prevent copying and
fraud. This requirement is not to be applied
to prescriptions sent to the pharmacy by fax,
email, or verbally.
4
All prescriptions flled in Arizona must have a
paper version that must be fled and kept for at
least seven years. Prescriptions must be issued
a serial number, and the date the prescription
was flled must be placed on the prescription
before fling. Prescriptions should be fled in the
order in which they were dispensed. This fle
may be maintained electronically by scanning
the prescription images, as long as they are
readily retrievable upon request by the Board of
Pharmacy or its agents. These regulations also
apply to hospital pharmacy prescription records.
Prescriptions for non-controlled substances
written by prescribers licensed by appropriate
licensing boards in Canada or Mexico may
be flled in Arizona. Prescriptions written for
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federally controlled substances by Canadian or
Mexican prescribers may not be flled in Arizona.
Canadian and Mexican prescriptions must be kept
in a separate fle for retrieval, and must be kept
for seven years as well.
Generic substitution and DAW
Prescriptions flled in Arizona should be
dispensed as they are written if the prescriber
writes on the prescription any variation of the
terms DAW, dispense as written, or do not
substitute. The generic product substituted for
the brand name written on the prescription must
FDA-approved and listed as bioequivalent to
the brand name product in the Orange Book. If
a generic product is given, the price for both the
brand name and generic product must be given to
the patient if the prescription is not billed to an
insurance plan.
The generic product may not be given if the
manufacturer does not print an expiration date on
the products packaging, or if the manufacturer
does not have a program for the recall of unsafe
or fawed products. The patient may choose to
have the brand name dispensed if the prescriber
did not specify that the brand name is medically
necessary.
Reflls and valid time frame for flling
prescriptions
All prescriptions flled in Arizona have a valid
time frame in which the original prescription and
available reflls may be flled, depending on the
type of medication ordered. Prescriptions flled in
Arizona for non-controlled substances are valid
for one year from the written date, and may only
be reflled within this time frame.
Prescriptions for schedule III-V controlled
substances are valid for six months from the
written date, and may be reflled up to fve times.
Schedule II prescriptions are valid for 90 days
from the written date and may not be reflled.
Dispensing controlled substances without
prescription
In the state of Arizona, certain controlled
substances can be dispensed without a
prescription under specifc conditions. Patients
who are at least 18 years old can purchase certain
controlled substances from a pharmacist if all of
the following criteria are met:
It must be requested for legitimate medical
treatment.
No more than 240 mL or 48 dosage units of
any controlled substances containing opium,
or 120 mL or 24 dosage units of any other
controlled substances may be dispensed to
the same person within 48 hours.
No more than 120 dosage units of any
product that contains only ephedrine may be
dispensed within 30 days.
Any patient who is not known to the
pharmacist must provide identifcation and
proof of age.
A record book must be used to collect
information about the person purchasing
the controlled substance, including name
and address of the person purchasing the
product, the quantity and name of the product
purchased, the date the purchase was made,
and the name or initials of the pharmacist
overseeing the sale.
The bottle must be labeled with the
pharmacys name and address, date product
was dispensed, serial number, prescribers
name, patients name, directions for using
the product, and any warning statements
necessary. If a controlled substance, it must
also include the federally required warning:
Caution: federal law prohibits the transfer of
this drug to any person other than the patient
for whom it was prescribed.
Pseudoephedrine is regulated in Arizona
because it is a common product used in the
manufacture of methamphetamine. Regulations
have been put in place to deter people from
purchasing large amounts of pseudoephedrine
for methamphetamine production to decrease the
production of this drug in Arizona.
In most instances, Arizona state regulations on
pseudoephedrine sales are less restrictive than
federal laws, so federal laws must be followed in
Arizona. These regulations include:
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All sales must be recorded in a logbook.
The logbook may be electronic or on
paper.
It must be readily retrievable and
maintained for at least two years.
It must record the name and address of
the person purchasing pseudoephedrine,
the date and time the sale was made,
the name and quantity of the product
purchased, and include the signature of
the purchaser.
A state-issued photo identifcation card,
drivers license, or passport must be
presented at time of purchase.
All products containing pseudoephedrine
must be kept behind the counter or in a
locked cabinet, and can only be sold under
the supervision of a licensed pharmacist.
There are strict limits to how much
pseudoephedrine can be purchased at once.
No more than 9 grams of pseudoephedrine
may be purchased by a single person within
a 30-day period, and no more than 3.6
grams may be purchased per person per
day. This is to decrease the availability of
pseudoephedrine and limit its use in the
production of methamphetamine.
Mail order or Internet retailers are limited
to shipping no more than 7.5 grams of
pseudoephedrine within a 30-day period.
These rules do not apply to prescriptions
written for pseudoephedrine only
for over-the-counter sales without a
prescription.
Patient counseling
Patient counseling must occur on all new
prescriptions dispensed to the patient. Counseling
must be conducted by a licensed pharmacist or
intern under the direct supervision of a licensed
pharmacist, and should include an overview of
the medication, including its brand and generic
names, directions for use, contraindications as
appropriate, and adverse effects. The patient or
his or her representative should be given time to
ask questions and receive appropriate answers.
Counseling is not required on reflls unless there
is a change in directions or dosage.
Transferring prescriptions
Prescriptions may be transferred between
pharmacies by pharmacists or graduate interns.
When a prescription is transferred out, it must
be invalidated by the transferring pharmacy
by writing VOID on the original prescription
hard copy, or ensuring it is invalidated in the
pharmacys dispensing computer system.
The name, address, and phone number or other
means of identifcation of the receiving pharmacy
shall be copied onto the back of the hard copy
prescription or saved in the pharmacys computer
system.
The prescription order for a non-controlled
substance taken down by the receiving pharmacy
must include the word transfer, the original
written date of the prescription, the frst and
last dates the prescription was dispensed, the
original number of reflls, the number of reflls
remaining, the name, address, and phone number
of the original pharmacy or other identifying
information, the prescription number at the
original pharmacy, the name of the pharmacist or
graduate intern the prescription was transferred
from, and the name of the receiving pharmacist
or graduate intern.
Prescriptions for Schedule III, IV, and V
controlled substances may only be transferred
between two licensed pharmacists, and may only
be transferred one time. The same information as
for a non-controlled substance is recorded for a
controlled substance, and both pharmacists must
record the DEA number of the other pharmacy on
the transfer order.
Prescriptions may be transferred into Arizona
from out of state if they meet all of the above
requirements for prescription transfers and are
prescribed by a prescriber with prescriptive
authority in Arizona. See section titled Who
can prescribe in Arizona? for details on what
prescribers have prescriptive authority in
Arizona.
Record keeping requirements
All records must be kept in a readily accessible
area for seven years. This includes prescription
hard copies, daily sales records, immunization
records, prescription transfer records, logbooks
for pseudoephedrine and controlled substance
sales, and any records required to be kept by
federal or state laws.
Pharmacy licensure
All pharmacies, drug wholesalers, drug storage
facilities, and drug manufacturers in Arizona
must be licensed with the Board of Pharmacy,
and these licenses must be renewed every
other year. Pharmacies not located in Arizona
that deliver medications to patients in Arizona
must also be registered with the state Board of
Pharmacy in Arizona.
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Application for a license to operate a pharmacy,
drug wholesaler, drug storage facility, or drug
manufacturing plant must include the following:
The name of the person responsible for
the operation of the facility, including any
licensed pharmacists responsible for its
operation.
The location of the facility to be licensed,
including physical street address.
A description of the activities to be performed
at the facility.
If a company with several facilities is seeking
licensure, a separate application must be
completed for each location desiring licensure.
There are several types of permits that may be
issued by the Board of Pharmacy. These include:
A permit to sell non-prescription medications
in the original package. Businesses that
hold this permit are not required to sell their
products at one fxed location.
A pharmacy permit can be issued and is
necessary to operate a full service pharmacy.
Limited service pharmacy permits may be
issued to pharmacies that are only practicing
a limited portion of pharmacy practice, such
as a closed-door pharmacy that only offers
patient counseling and does not dispense
medications.
Full service wholesale drug permits may be
issued to wholesalers that stock prescription
and nonprescription medications.
Nonprescription drug wholesale permits can
be issued to wholesalers that only want to
stock nonprescription medications.
Drug manufacturer permits may be issued
to facilities involved in the creation of
prescription and nonprescription drug
products.
A drug packager or pre-packager permit may
be issued to a person or business registered
with the Food and Drug Administration
(FDA) and authorized by the FDA to change
the original manufacturers packaging of
a drug product to re-sell the repackaged
product to a business that is authorized to sell
repackaged medications.
A compressed medical gas distributor or
supplier permit can be issued to facilities
interested in selling or distributing
compressed medical gasses, such as oxygen.
Permits can be revoked if it is discovered that a
medical provider is receiving compensation from
a pharmacy for prescribing certain products. If a
permit-holders business is closing or otherwise
ceasing to operate, the permit should be
surrendered immediately, the Board of Pharmacy
must be notifed, and all drug products and
signage should be removed or destroyed.
Pharmacist licensure and continuing
education requirements for pharmacists
Pharmacists can obtain their licenses from the
Arizona Board of Pharmacy. To be eligible for a
pharmacist license, applicants must graduate from
an accredited school of pharmacy recognized
by the board, successfully complete a practical
experience program supervised by a licensed
pharmacist, pass the pharmacist licensure exam
and state jurisprudence exam, pay a pharmacist
application fee to the Board of Pharmacy, and be
of good moral character.
All pharmacists must renew their licenses every
other year, and all pharmacist licenses expire
on October 31. To be eligible for renewal,
pharmacists must complete three continuing
education units or CEUs (30 hours) every two
years, with at least 0.3 CEUs (three hours) on
the topic of pharmacy law. Proof of continuing
education completion should be retained for fve
years, and credits may not be carried over to the
next renewal period.
Failure to renew a pharmacist license by October
31 of a renewal year may result in additional
fees. Pharmacists who have not been practicing
pharmacy for more than one year must complete
a board-approved training program of 400 hours
before they are eligible to resume practice as a
pharmacist.
Pharmacists who serve as the pharmacist-in-
charge at a pharmacy must report this position
to the Board of Pharmacy. The pharmacist in
charge is considered the responsible manager of
the pharmacy. If this position is terminated, the
pharmacist must report this change to the Board
of Pharmacy as well.
Pharmacists who wish to serve as preceptors to
pharmacy interns must register for a preceptor
license with the Board of Pharmacy. These
pharmacists are responsible for practical
instruction of the intern, and are to act as a
teacher and mentor to the student. Preceptors are
also able to verify intern hours worked by the
pharmacy intern. To be eligible for a preceptor
license, the applicant must be a licensed
pharmacist with an unrestricted license and must
have at least one year of experience actively
working as a licensed pharmacist. Pharmacists
with preceptor licenses working in a community
setting may only be a preceptor to two pharmacy
interns per calendar quarter.
Pharmacy intern responsibilities
Pharmacy interns can work in a pharmacy
under a licensed pharmacist once they become
registered and licensed with the Board of
Pharmacy. To be eligible for an intern license,
applicants must be enrolled in an accredited
school of pharmacy recognized by the Board of
Pharmacy. Graduate intern licenses may be issued
to applicants who have graduated from a school
of pharmacy approved by the board.
A total of 1,500 intern hours must be recorded
with the Board of Pharmacy before an intern
is eligible for licensure as a pharmacist. No
more than 500 hours may be recorded per
quarter (three months). Pharmacy interns can
only register hours worked if working under a
preceptor, a licensed pharmacist registered with
the Board of Pharmacy with a preceptor license.
Intern hours may be registered after the beginning
of the frst year of professional pharmacy
education, and after the pharmacy intern receives
a Board of Pharmacy-issued intern license.
Intern licenses are issued for fve years, and
may be issued for an additional year with board
approval. Intern licenses are not eligible for
renewal as the intern license is used for students
studying to become pharmacists. Student who
do not complete their education within six years
must explain to the Board of Pharmacy that they
intend to continue working toward completing
their education and becoming a pharmacist for a
renewal to be issued.
The pharmacy intern may perform the following
tasks under the immediate supervision of a
licensed pharmacist:
Dispense and sell medications, medical
devices, and poisons to patients.
Compound medications.
Perform duties of a pharmacist, as long as a
licensed pharmacist directly supervises them.
Pharmacy interns are to be trained in the practice
of pharmacy during their intern hours worked.
This includes:
The manufacture and sale of medications and
medical devices.
Dispensing and compounding medications.
Clinical pharmacology.
Providing information on medications to
patients and health care providers.
Record keeping and completing federal and
state-mandated reports.
Maintaining compliance with the law.
Pharmacy technician responsibilities
Pharmacy technicians, pharmacy technician
trainees, and certifed pharmacy technicians must
be registered and licensed with the Board of
Pharmacy to work in a pharmacy, and the license
must be renewed every other year.
Before beginning work in a pharmacy, pharmacy
technicians and trainees must sign and date
a statement showing they have reviewed the
Board of Pharmacy regulations for pharmacy
technicians, the job description for their position
in the pharmacy, and the pharmacys handbook
of policies applicable to pharmacy technicians.
These policies should include information on
employer expectations for pharmacy technicians,
activities that technicians may perform, how
to report and avoid medication errors, how to
maintain confdentiality of patient information,
security procedures, federal and state regulations,
dispensing procedures, and maintaining the
pharmacy inventory and storage.
People interested in working as a pharmacy
technician must be 18 or older, possess a high
school diploma or GED certifcate, and be of
decent moral character. For interested persons
to be eligible to apply for a pharmacy technician
license, the person must complete a training
program for pharmacy technicians that meets
state-specifc standards, and take the Pharmacy
Technician Certifcation Board exam (PTCB
exam) and pass with a satisfactory score.
Pharmacy technicians in training must apply for a
pharmacy technician trainee license to complete
their training in a pharmacy.
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After completing a pharmacy technician training
program and passing the PTCB exam, pharmacy
technicians may apply for a pharmacy technician
license with the Board of Pharmacy. The
license application must include demographic
information for the person applying, any felony
offense or drug-related offences committed or
pending, information on whether the person
applying has ever had a revoked or suspended
pharmacy license or a denied pharmacy
technician application, the pharmacy name and
location where the applicant will work, the
verifed signature of the person applying, the
date, and the license fees for the license issuance
and wall hanging license to be displayed in the
pharmacy.
The Board of Pharmacy will determine eligibility
for licensure and make a decision within seven
days of receiving the application. Once the
Board of Pharmacy issues a license number, the
pharmacy technician may begin working. Wall
licenses should be mailed within 14 days of
license number issuance.
Pharmacy technician licenses must be renewed
every other year, and renewal must be completed
by flling out a renewal form and including the
necessary renewal fees. All pharmacy technician
licenses must be renewed by October 31 of their
renewal year. If license renewal is not completed
by November 1, the pharmacy technicians
license will be suspended and a late fee will be
added to the renewal fee.
Pharmacy technicians may perform the following
tasks when working under the supervision of a
licensed pharmacist:
Accept approval of refll authorizations
from a prescriber or representative. The
approval may be accepted electronically or
verbally, and must include the prescribers
name, patients name, drug name, quantity,
additional reflls, and name of the prescribers
representative.
Enter information into a patients profle.
Document the prescription number and
dispense date on the original prescription
order.
Enter prescription information into a
patients fle to create a prescription label for
verifcation by a pharmacist.
Reconstitute powdered medications if
ingredients added are verifed by a pharmacist
before reconstitution, and the fnal product is
verifed after reconstitution.
Count out or pour medications into bottles for
verifcation by a pharmacist.
Pre-package medications for verifcation by a
pharmacist.
Prepare medication for dispensing in the
inpatient hospital setting for verifcation by a
pharmacist.
NOTE: Pharmacy technicians cannot record
new prescriptions called in by a prescriber.
This includes any changes made to a refll
prescription, because a reflled prescription
that has been changed is considered a new
prescription.
Technicians must wear a nametag with their name
and title while working as a pharmacy technician.
Pharmacy technician training programs may be
conducted at the pharmacy where the technician
will work, or off-site at a training school.
Training programs must teach the technician
the tasks they will be required to perform in
their employment and discuss the policies and
procedures and activities that may be completed
by a pharmacy technician as implemented by the
Board of Pharmacy. Technicians must be assessed
on their knowledge of these tasks and retrained if
they do not demonstrate competency.
The pharmacist-in-charge who is training the
pharmacy technician must keep a record of
the progress of the trainee and sign off on a
document when the technician has completed the
training program successfully. Documentation
of successful completion of the training program
must be saved for possible inspection by the
Board of Pharmacy, and a copy must be provided
to the technician as well.
Technicians who wish to compound prescription
medications must successfully pass a training
program onsite at the pharmacy where they are
employed, or off-site at a pharmacy technician
training school. The training program must
address the following guidelines:
The tasks the pharmacy technician will be
required to perform.
Preparation of the area to be used for
compounding of prescription medications.
Preparation of the products to be used in the
compounding of a prescription product.
Aseptic technique to be used for the
preparation of prescription products in a
sterile environment.
How to properly package and label
prescription products.
Proper cleanup of the medication
compounding area, including procedures for
hazardous waste cleanup.
The technicians training progress must be
documented by the pharmacist in charge, and
program completion must be recorded and signed
by the pharmacist in charge. Documentation of
the completion of training programs must be
maintained for possible inspection by the Board
of Pharmacy.
NOTE: Only pharmacy technicians who
have successfully completed a medication
compounding training program may compound
prescription medications for fnal verifcation by
a pharmacist!
Pharmacy technician continuing
education requirements
In Arizona, pharmacy technicians need to obtain
a license from the Board of Pharmacy to work in
a pharmacy. To maintain their license, technicians
must complete 20 hours of continuing education
every other year, with two hours on the topic of
pharmacy law, to be eligible for license renewal.
Proof of continuing education completion should
be retained for fve years, and credits may not be
carried over to the next renewal period.
NOTE: Address changes and changes in
employer for any licensed pharmacy employee
must be reported to the Board of Pharmacy
within 10 days.
Pharmacists administering immunizations
In the state of Arizona, pharmacists who
are certifed to give immunizations may
immunize adults as recommended by the adult
immunization schedule or international travel
recommendations issued by the U.S. Centers for
Disease Control. These immunizations may be
issued without a prescription.
Certifed pharmacists may immunize children
aged 6-18 years with fu immunizations or
immunizations necessary during a public health
emergency without a prescription order. Other
immunizations may be given with a prescription
order from the patients prescriber.
Pharmacists must be trained and certifed in
immunization delivery before they are eligible
to apply for a certifcate to immunize patients.
The training program must include the following
information:
Immunology and the immune response
involved in immunization of patients.
Names of available vaccines, dose, side
effects, immunization schedule, and how
immunity occurs with each available vaccine.
How to respond to emergencies that occur
from the administration of a vaccine,
including how to administer epinephrine or
diphenhydramine to slow the effects of an
allergic reaction to a vaccine.
How to administer intramuscular and
subcutaneous injections.
Proper record keeping requirements and
reporting requirements for adverse effects
and prescriber notifcation.
NOTE: The training program developed by
the American Pharmacists Association (APhA)
meets the requirements for immunization training
programs in Arizona.
Pharmacists who have passed the immunization
training program are eligible for an immunization
certifcate from the Board of Pharmacy as long
as they have a current unrestricted pharmacist
license in Arizona and have a current certifcation
in basic cardiopulmonary resuscitation (CPR).
Pharmacists must apply for their immunization
certifcate with the Board of Pharmacy and
receive board approval before administering
immunizations to patients in Arizona.
Graduate interns may administer vaccinations
after completion of a certifcation course
and certifcation by the Board of Pharmacy,
but only under the supervision of a licensed,
immunization-certifed pharmacist. Graduate
interns may also administer epinephrine or
diphenhydramine in an emergency situation
under the supervision of a licensed, certifed
pharmacist.
Once graduate interns or pharmacists are
certifed to administer immunizations, the
certifcation must be maintained with the Board
Page 6 Elite
of Pharmacy and kept in the pharmacy for review
by patients or the Board of Pharmacy if needed.
Immunization certifcations must be renewed
every fve years. To be eligible for renewal, a
renewal application must be sent to the Board of
Pharmacy including a current certifcate in basic
cardiopulmonary resuscitation and completion of
0.5 continuing education units (5 hours) on the
administration of immunizations.
Immunizations given must have accurate records
maintained at the pharmacy. Each immunization
given must have documentation that includes:
The patients name, address and birth date.
The date the immunization was given and the
injection site.
The name of vaccine given as well as the
dose, lot number, and expiration date.
The name and address of the patients
primary care physician.
The name of the pharmacist or graduate
intern who gave the immunization.
A record of consultation with the patient
that determined the patient was eligible for
vaccination.
The date and time vaccination information
was sent to the patients primary care
provider.
Consultation information given to the patient,
including the title and date of the vaccine
information sheet (VIS).
A copy of the parent consent form for
vaccines given to minors.
Certain vaccines require a prescription for a
pharmacist to immunize an adult. These include
the Japanese encephalitis vaccine, the rabies
vaccine, yellow fever vaccines, and typhoid
vaccines. After receiving a prescription order
for these vaccines, a pharmacist is allowed to
immunize the patient.
6
All other vaccines may
be administered to an adult patient without a
prescription, according to the recommendations
published by the U.S. Centers for Disease
Control.
Documentation of vaccinations given to patients
must be sent to the patients primary care
physician within 48 hours of immunization.
Records must be kept in a readily accessible
place for at least seven years for possible
inspection by the Board of Pharmacy.
Conclusion
Arizona state pharmacy laws dictate the
daily operations of pharmacies and pharmacy
employees. It is important to stay up-to-date on
new pharmacy laws that govern daily practice
to serve patients within the limits of the law and
obtain continuing education credits to maintain
licensure. Information on new pharmacy laws in
Arizona can be found on the Arizona Board of
Pharmacys website at http://www.azpharmacy.
gov/. A copy of the current Arizona state
pharmacy law book can be found at http://www.
azpharmacy.gov/pdfs/law%20book%208-9-2012.
pdf.
References
1. Arizona State Board of Pharmacy. Prescriptive Authority of Health Professionals in
Arizona. February 2013. Accessed at http://www.azpharmacy.gov/pdfs/prescriptive%20
authority%20chart%20(02-2013).pdf on July 10, 2013.
2. Arizona Regulatory Board of Physician Assistants. FAQs: Information Regarding PA
Prescribing Changes. Accessed at http://www.azpa.gov/FAQ/PAPrescribingFAQ.aspx
on July 12, 2013.
3. Arizona State Board of Pharmacy. Arizona State Board of Pharmacy Revised Statue.
August 9, 2012. Accessed at http://www.azpharmacy.gov/pdfs/law%20book%208-9-
2012.pdf on July 10, 2013.
4. Berman, Suzi. Tamper Resistant Prescription Pads Memo. April 27, 2012. Accessed
at http://www.azahcccs.gov/commercial/Downloads/PharmacyUpdates/TRPP_
Memo_4_27_2012.pdf on July 14, 2013.
5. Glendale Police Department Pseudoephedrine. Accessed at http://www.glendaleaz.
com/police/pseudoephederine.cfm on July 13, 2013.
6. Arizona State Board of Pharmacy. Immunizations or Vaccines Requiring Prescriptions
for Pharmacist Administration. Article 13, Section R9-6-1301. Effective October 5,
2009. Accessed at http://www.azpharmacy.gov/pdfs/R9-6-1301VaccineList.pdf on
July 14, 2013.
OVERVIEW OF
ARIZONA PHARMACY LAW
Final Examination Questions
Choose the best answer for questions
1 through 5 and mark your answers on the
Final Examination Sheet found on page 63
or complete your test online at
www.elitecme.com.
1. How many members of the Arizona Board
of Pharmacy are pharmacists?
a. Nine.
b. Six.
c. Two.
d. One.
2. A prescription for oxycodone, a Schedule
II controlled substance, is brought to the
pharmacy to be flled. For how long is this
prescription valid?
a. One year from the written date.
b. Six months from the written date.
c. Six months from the frst fll date.
d. Ninety days from the written date.
3. How long must prescription hard copies be
kept in a readily accessible area?
a. Two years.
b. Three years.
c. Seven years.
d. Nine years.
4. How many hours of continuing education
must be completed by a pharmacy
technician every other year?
a. 15 hours.
b. 2 hours.
c. 20 hours.
d. 30 hours.
5. Which of the following vaccines requires a
prescription to be administered to an adult
patient?
a. Tetanus.
b. Herpes zoster.
c. Infuenza.
d. Japanese encephalitis.
RPTAZ02AZE13
Elite Page 7
CHAPTER 2
ANTIDEPRESSANT DRUG THERAPY FOR
PHARMACY PROFESSIONALS
(3 CONTACT HOURS)
By Katie Ingersoll, RPh, PharmD, and Staff Pharmacist
for national chain
0761-9999-13-243-H01-T
666-9053. This lesson is $15.00.
education credit.
Learning objectives
! Defne major depression.
! Describe the different types of depression.
! Discuss the incidence and prevalence of
major depression.
! Identify the signs and symptoms of major
depression.
! Discuss possible causes of major depression.
! Explain how major depression is diagnosed.
! Identify the classifcations of drugs used to
treat depression.
! Explain the action of each classifcation of
antidepressant drug therapy.
! Describe the side effects of each classifcation
of antidepressant drug therapy.
! Identify herbs used in the treatment of
depression.
! Explain the potential reactions when using
herbs for the treatment of depression.
! Summarize important considerations for
patient education.
Introduction
Nicole is a pharmacy technician who works
in a large pharmacy that is part of a major
drugstore chain. Several people approach the
pharmacy entrance. She recognizes 35-year-
old Mr. Davidson, who had a prescription flled
for antidepressant medication last week. His
wife and mother accompany him. His mother
appears impatient and angrily tells him, I
dont understand this depression business.
Everybody feels sad sometimes, but you just have
of depression will have another one.
25
After
a patient experiences a second episode of
depression, there is a 70 percent chance that
the depression will return.
24
2. Recurrent depression: Two or more
depressive episodes occur, separated by at
least two months of normal or near-normal
functioning.
11
3. Seasonal affective disorder (SAD): Changes
in mood in persons who are depressed may
be related to the seasons of the year. Patients
who experience season-related depression are
usually depressed during the fall and winter
and feel better during the spring and summer.
It is hypothesized that SAD is caused by a
reduction in the brains melatonin secretion,
which is triggered by sunlight. Since there
is less sunlight during the fall and winter,
SAD is more prevalent during these months.
However, there have been rare reported cases
of SAD occurring during the spring and
summer.
10
Some patients experience only one episode of
major depression and never have a recurrence
of the problem, while others may experience
multiple episodes. Still others may suffer chronic
depression that lasts a lifetime. It is not possible
to determine whether one episode of major
depression will develop into a lifetime condition
for each patient.
4,24,27
Incidence and prevalence of major
depression
Mental illness, defned as diagnosable mental
disorders, causes more disability in developed
countries than any other group of illnesses,
including cancer and cardiac disease. In fact, it
is estimated that 25 percent of all adults in the
United States will develop at least one mental
illness during their lives.
1
Depression is one of
the most common mental illnesses, affecting
nearly 18 million Americans, or one out of every
six people.
4,8
Therefore, it is likely that health
care professionals, at some point in their careers,
will work with patients who are experiencing
depression.
The number of reported cases of depression has
been increasing every year since the early 20th
century.
Depression alert! The incidence of depression
may be much higher than actually reported.
It is estimated that only half of all persons
who meet the criteria for diagnosis of major
depression (according to the Diagnostic and
Statistical Manual of Mental Disorders, 4th ed.)
request treatment. This makes it very diffcult
to accurately determine the true incidence of
depression.
8
Culture and socioeconomic conditions play a
signifcant role in the reporting and treatment
of depression. In some cultures and countries,
mental illness may not be openly discussed or
acknowledged. For example, in Eastern countries,
depressive symptoms are often reported as a
loss of energy or various types of pains rather
than a mental health issue.
8
It is important that
to get over it. You dont need medicine. Mrs.
Davidson looks anxiously at her husband and
asks her mother-in-law to help her make some
purchases. After the two women walk away, Mr.
Davison becomes tearful and shakes his head.
This medicine isnt working. Ive been taking
it for over a week now and theres no difference.
I cant take feeling like this anymore. Im just a
weakling, like my mother says. Nicole is very
concerned. She gently tells Mr. Davidson, You
are not a weakling. Depression is an illness that
can be treated with your medication, but it may
take time for you to start to feel a difference.
Please sit down. I am going to have the
pharmacist come and talk to you about how your
medicine works.
Fortunately for Mr. Davidson, an alert,
knowledgeable pharmacy technician was able
to initiate actions that will help him. Nicole
knows that depression is not something one
just gets over and that it can take weeks for
antidepressants to produce therapeutic effects.
2,9,19

Therefore, Nicole has taken the appropriate steps
to ensure Mr. Davidsons safety and help him get
the most beneft from his medication.
Being able to help Mr. Davidson and other
patients with major depression requires not
only knowledge of antidepressant drugs, but
also knowledge of major depression disorder
as well. Causes, contributing risk factors, and
presenting signs and symptoms are all issues
pharmacy technicians must be aware of. Such
knowledge helps to provide patients with the
best possible care and to help them achieve the
best possible outcomes. Pharmacy technicians
who are knowledgeable of the nuances of major
depression will put themselves in a better position
to not only serve their patients and attend to their
needs as they arise, but also prevent medication
errors and enhance patient care.
This course will discuss the defnition and
diagnosis of major depression, its prevalence,
signs and symptoms, and major causes of this
condition. A thorough discussion of available
treatments for major depression will be discussed
as well, including a description of the major drug
classes, drugs in each class, side effects, and
major drug interactions.
What is major depression?
Major depression, also referred to as unipolar
disorder, is a disorder characterized by persistent
feelings of sadness and worthlessness, anxiety,
low self-esteem, diffculty concentrating, and
lack of pleasure or no interest in normal daily
activities.
4,21
There are three types of depressive episodes.
These are single, recurrent and seasonally
patterned.
10
1. Single depressive episode: A person
experiences a limited episode of depression
that occurs and ends within a fxed period of
time. After this one episode, the person does
not experience depression again.10 However,
it is important to know that 50 percent to 60
percent of persons who have one episode
Page 8 Elite
health care providers do a careful and thorough
history and physical, including mental health
assessments, when evaluating patients health and
well-being.
Major depression affects all racial, ethnic and
socioeconomic groups. It is twice as common
in women as in men. However, the incidence of
depression in men increases with age, and the
incidence of depression in women decreases with
age. There is also a higher risk of depression in
patients with a family history of the disorder.
Major depression is 1.5 to 3 times higher in frst-
degree relatives (e.g., parents, siblings, children)
than in the general population. The incidence of
major depression is highest in single people and
in people who are divorced.
24
Depression occurs in all age groups, but its
onset is commonly frst identifed between the
ages of 24 and 44. The incidence of depression
and suicide among teenagers increases every
year. Experts hypothesize that this increase is
due to feelings of pressure to meet expectations
of parents and peers as well as self-esteem
problems.
7
Signs and symptoms of major depression
Marjorie is a 32-year-old assistant professor
of American literature at a large, prestigious
university. She is highly respected by her
colleagues and students and has published
several critically acclaimed books. She is
married and the mother of a 5-year-old daughter.
Her marriage had always been happy and her
daughter a source of great joy to both her and her
husband. However, for the past month, Marjorie
has complained that she feels exhausted and
emotionally drained. Marjorie spends most of
her time at home sleeping, and no longer has any
interest in spending time with her husband and
daughter. Her students are beginning to complain
that she has no interest in them or in teaching.
Marjories family and work colleagues are
concerned and urge her to see a doctor. Marjorie
responds by saying, What good will that do?
Theres nothing to enjoy about life anymore, and
a doctor isnt going to help me feel any better.
Marjorie seems to be experiencing a major
depressive episode.
The primary exhibiting symptoms of a major
depressive episode include:
4,24

Feelings of sadness, hopelessness and
worthlessness.
Disturbances in sleep patterns (either sleeping
too much or being unable to sleep).
Decreased attention to activities of daily
living.
Lack of participation and enjoyment in
previously pleasurable activities.
Weight loss or gain.
Agitation.
Fatigue.
Decreased self-esteem.
Diffculty concentrating or making decisions.
Lack of interest in sexual activity.
Suicidal thoughts.
Some patients with severe depression (about 9
percent of those effected) may have psychotic
symptoms, such as hallucinations or delusions.
These symptoms can be severe and may indicate
another mental health disorder, or simply an
adverse reaction to major depression. These
patients should be thoroughly evaluated by a
mental health professional.
24,27
Depression alert! Some patients with depression
may feel that life is no longer worth living and
attempt to take their own lives. About twice as
many women compared to men attempt to commit
suicide, but men who attempt suicide are more
likely to succeed in the attempt.
4
Suicide often
occurs just as depression begins to lift (e.g., after
antidepressants start to take effect). This may be
because of a lessening of the fatigue and inability
to concentrate associated with depression. As
the depression begins to lift, the patients energy
level and ability to concentrate increases, and
the ability to plan and implement a suicide
plan also increases. This is especially common
in adolescents and young adults, and a black
box warning on many antidepressants warns
caregivers to monitor patients closely for this
reaction.
2,4,24,27
Causes and diagnosis
Charlotte is a business manager who works
at a large university-affliated medical center.
She is having lunch with her best friend Anna,
a pharmacy technician with many years of
experience in a variety of health care settings.
Charlotte has had several recurrences of major
depression over a period of several years. It is
likely that she will need to take antidepressant
medication indefnitely. Charlotte is tearful and
confesses that her husband and teenage children
are starting to question why she is still taking
medication. My husband and the kids say Im
just babying myself. They keep telling me that I
have a good life and dont seem depressed. They
want me to stop taking medication. They say there
is no real reason for me to become depressed
again. Im beginning to wonder myself if I need
this medication. What really causes depression
anyway? Its just something emotional, isnt it?
I mean, theres no physical reason for me to
become depressed, is there? Anna responds by
explaining that there are a number of possible
causes of depression. She wants to help Charlotte
get the necessary patient education about major
depression, its possible causes and its treatment.
The exact cause of depression is not completely
understood, but research indicates that a
combination of factors, including family
history, psychosocial issues, concurrent physical
conditions, and biochemical factors infuence its
development. For example, depression may be
secondary to some medical conditions, such as
endocrine disorders and neurologic diseases. It
may follow a traumatic event, such as the death
of a loved one or divorce. Some medications,
such as anti-hypertensives and anti-parkinsonian
drugs, may trigger depression.
4,6,7
It is important
that health care professionals be aware of the
various factors that can lead to the development
of a major depressive episode.
As in the case of Charlotte in the preceding
scenario, patients need to be provided with
information about the possible causes and
risk factors of depression. Without such
education, patients may be tempted to belittle
the seriousness of major depression and to
discontinue necessary treatment. Discontinuing
antidepressant medications abruptly can cause
dangerous side effects and can put the patient at
risk of harming himself or herself. The following
factors may trigger a depressive episode or
contribute to a diagnosis of chronic depression.
Psychosocial stressors
Psychosocial stressors can trigger depression.
Depression is more common in patients who
have a history of signifcant trauma, such as
death of a loved one, divorce, physical abuse,
sexual abuse, or loss of income. Stress in the
workplace or home life can also contribute to
the development of depression.
4,7,27
The patients
history and a thorough discussion with the patient
about depressive triggers may pinpoint a specifc
bereavement or stressor that has triggered the
depression.
Physical medical conditions
Depression may occur secondary to a number of
physical medical conditions, such as:
4
Malignancies.
Endocrine disorders.
Neurologic diseases.
Bacterial infections.
Cardiovascular disorders.
Gastrointestinal disorders.
Anemias.
Persons dealing with physical illness should
also be monitored for signs and symptoms of
depression. Physical illness is a stressful state and
may very well trigger a depressive episode.
Medications
Gerald is diabetic. His disease has been well
controlled for many years by diet and oral anti-
diabetic medication. Gerald also suffers from
recurring episodes of major depression. His
physician believes that Geralds anti-diabetic
medication may be contributing to his depression.
Various medications used to treat physical and
other mental health illnesses can also cause
depression. It is important that pharmacy
personnel are aware of this potential side effect,
and pharmacists should include ways to monitor
for depression as part of patient education.
Patients who experience depression as a side
effect of other medications should discuss
their symptoms with their medical provider
immediately, before symptoms become severe.
Medications that may lead to depression include:
4
Anti-hypertensives.
Psychotropics.
Opioid and non-opioid analgesics.
Medications used to treat Parkinsons disease.
Cardiovascular medications.
Steroids.
Elite Page 9
Oral anti-diabetic drugs.
Cimetidine.
Chemotherapeutic drugs.
Depression alert! Substances such as alcohol
and illegal drugs can also cause depression.
4
Family history
Research shows that people whose parents suffer
from depression are more likely to develop
depression themselves. A patient with one parent
who has depression has a 27 percent chance of
developing a mood disorder, and if both parents
have a history of depression, the chance increases
to 54 percent.
7
As previously noted, major
depression is 1.5 to 3 times higher in frst-degree
relatives (e.g., parents, siblings, children) than in
the general population.
24

Biochemical factors
Although the exact biochemical infuence on the
development of depression is not known, most
researchers believe that some neurotransmitters,
particularly norepinephrine and serotonin, are
decreased in patients with depression. Under
normal conditions, neurotransmitters are released
to link with specifc neural receptors. If an
inadequate amount of neurotransmitters are
released or if the number of neural receptors is
decreased, depression may occur.
24
Diagnosis
Diagnosis is made based on a complete history
and physical and the use of psychological
screening tests, such as the Beck Depression
Inventory.
4
A patient is diagnosed as having
major depression when he or she meets the
criteria identifed in the Diagnostic and Statistical
Manual of Mental Disorders 4th edition. Some of
the criteria are:
4
A minimum of fve of the following
symptoms must have been present during the
same two-week period and must be a change
from the patients normal pattern of behavior
and functioning:
Depressed mood most of the day, nearly
every day.
Signifcantly reduced interest in or
pleasure in activities of daily living.
Signifcant loss or gain of weight when
not dieting.
Sleep disturbances, such as sleeping too
much or not being able to sleep.
Fatigue or energy loss.
Psychomotor agitation or retardation
experienced almost every day.
These symptoms do not meet the criteria
for a mixed episode (when symptoms of
depression alternate with symptoms of
mania).
These symptoms signifcantly interfere with
the patients ability to function at work, at
home and in social situations.
These symptoms are not directly due to the
effects of a general medical problem or due
to substance abuse (such as illegal drugs).
Depression alert! The preceding criteria are not
all-inclusive. For complete diagnostic criteria,
refer to the Diagnostic and Statistical Manual of
Mental Disorders 4th ed.
4
The prevalence of depression makes it almost a
certainty that pharmacy technicians, no matter
their practice setting or specialty, will care
for persons who are currently experiencing
this disorder. Therefore, it is imperative that
all pharmacy technicians be knowledgeable
about the types of medications prescribed for
major depression, their actions, dosage, side
effects and potential adverse interactions. This
education program provides information about
the pharmacological interventions for major
depression, including herbal preparations.
Antidepressant pharmacology
Mrs. Adams has been taking antidepressant
medication for several years. Her physician
evaluates her on a regular basis, and believes
that she suffers from chronic depression. This
means that Mrs. Adams may need to take
medication for the rest of her life. When Mrs.
Adams comes to the pharmacy to have her
antidepressant prescription reflled, she asks the
pharmacy technician, How long is this going to
go on? I think I should stop taking these stupid
pills. I feel fne now. Mrs. Adams should be
referred to the pharmacist for appropriate patient
education on the nature of her depression as well
as the need to keep taking her antidepressant.
Prescription antidepressant medication is
the most common treatment intervention for
depression. About 80 percent of patients who take
antidepressants report an improvement in their
symptoms.
9
Treatment length varies among patients.
Treatment for an initial depressive episode may
last from six months to a year, and recurrent
episodes may require two years of treatment
with antidepressants. Chronic depression may
necessitate life-long treatment, as in the case of
Mrs. Adams in the preceding scenario.
9
It may take from one to eight weeks for
antidepressant medication to become fully
effective, depending on the dosage and the
patients response to the medication. Patients
should be thoroughly counseled on the time for
treatment to become fully effective, as this time
period is often diffcult for patients to cope with.
Drugs are generally prescribed initially at a low
dose, which is gradually increased according to
the patients tolerance and response to the drug.
Patients should be taught that therapeutic effects
are not immediately apparent. Sometimes the
antidepressant initially prescribed is ineffective,
and other drug options must be prescribed to
achieve the desired therapeutic effect.
2, 9
Drug alert! Patients on antidepressant
medication must be carefully monitored. In some
cases, antidepressants may increase the risk for
suicidal ideation, particularly in young adults
and children.
2,9,19
The Food and Drug Administration (FDA)
mandates that all antidepressants carry a warning
that some children, adolescents and young adults
may be at increased risk for suicidal ideation.
All patients, however, should be monitored
meticulously for any increase in depression or
unusual behavior, particularly during the frst few
weeks after antidepressant therapy is initiated.
2,13
Antidepressant medications include the
following:
2,9,19,24
SSRIs: Selective serotonin reuptake
inhibitors.
Cyclic antidepressants.
Atypical antidepressants.
MAOIs: Monamine oxidase inhibitors.
SNRIs: Serotonin and norepinephrine
reuptake inhibitors.
Drug alert! Antidepressants are sometimes
prescribed to treat conditions other than
depression, such as panic disorder, post-
traumatic stress disorder (PTSD), anxiety
disorders, obsessive-compulsive disorder, and
premenstrual dysphoric disorder.
2,19

Age-related concerns
Antidepressant use in children and adolescents
requires especially careful monitoring. However,
many medications have not been studied or
approved for use with children. Researchers are
not sure how these medications affect a childs
growing body. Physicians often will prescribe
an FDA-approved medication on an off-label
basis for children even though the medicine is not
approved for the specifc mental disorder or age
group. Young people may have different reactions
and side effects than adults and are at somewhat
greater risk for suicidal ideation when taking
antidepressants.
There is a black box warning on antidepressants
that adolescents and young adults should be
closely monitored when starting antidepressants
because of the increased risk of suicidal attempts.
It is very, very important that parents and other
caregivers be taught to monitor children for
any signs that they are thinking of harming
themselves.
2,9,19
Because older people often have more medical
problems than other groups, they tend to
take more medications than younger people,
including prescribed, over-the-counter nutritional
supplements and herbal preparations. As a result,
older people have a higher risk for experiencing
adverse drug interactions, skipping doses, or
overdosing.
Older people also tend to be more sensitive
to medications and their side effects. For
example, dizziness can be a side effect of many
antidepressants. Young patients may be able to
handle this side effect without problems, but
it can put older adults at a higher risk of falls,
potentially causing injury. Even healthy older
people react to medications differently than
younger people because their bodies may process
drugs more slowly. So lower or less frequent
doses may be prescribed for older patients.
2,9,17,24
Sometimes memory problems affect older people
who take medications for mental disorders. An
older adult may forget his or her regular dose
Page 10 Elite
or take too much or not enough. A good way
to keep track of medicine is to use a seven-day
pillbox, which can be bought at any pharmacy.
At the beginning of each week, older adults or
their caregivers fll the box so that it is easy to
remember what medicine to take each day. Many
pharmacies also have pillboxes with sections for
medications that must be taken more than once a
day, and some pharmacies even offer services to
fll pillboxes for patients or package medications
in easy to use blister packs.
2,9,17,24
Pharmacy personnel should make it a point to
offer suggestions to help make it easier for older
patients (or patients of any age, for that matter)
to remember to take their medications as ordered.
They should not wait for patients to ask. Instead,
offer suggestions and initiate conversation about
ways to properly take mediations.
Selective serotonin reuptake inhibitors
(SSRIs)
The most commonly prescribed antidepressants
as well as the newest classifcation of
antidepressants are SSRIs.
13,24
SSRIs are
considered to be generally safe and were
developed to cause fewer side effects than other
classifcations of antidepressants. This makes
SSRIs particularly benefcial options for older
patients.
13,24
They work by blocking central nervous
system (CNS) reabsorption (reuptake) of the
neurotransmitter serotonin in the brain. This
makes more serotonin available for use by the
brains neurotransmitters. Research indicates
that people who suffer from depression dont
have adequate levels of neurotransmitters in the
brain, such as serotonin.
24
Altering the balance
of serotonin is believed to increase the brains
ability to send and receive various chemical
messages. This helps to alleviate depression.
These drugs are referred to as selective because
they primarily have an impact on serotonin, not
on other types of neurotransmitters.
2,9,13,19

Jason is a 16-year-old high school student
diagnosed as suffering from major depression.
After taking an SSRI for about two weeks, his
parents notice that his energy has returned and
there is an improvement in his mood and ability
to concentrate. After school one afternoon, Jason
attempts to take his own life by swallowing a
large number of sleeping pills he found in his
parents medicine cabinet.
All patients, especially children, adolescents,
and young adults, must be monitored for an
increase in suicidal thoughts and actions after
starting antidepressant drug therapy. Although
his depression was not fully resolved, Jasons
energy level increased and his ability to
concentrate improved, so he had the energy and
focus as well as depressive thoughts to plan and
carry out a suicide attempt. The importance of
monitoring for suicidal thoughts and behaviors
cannot be stated often enough! Parents, other
family members, teachers and friends may be
relieved to see that a patients symptoms are
diminishing. But an important aspect of patient/
family education is to explain why the danger of
suicide actually increases just as the depression
starts to lift.
SSRIs may produce positive changes in as little
as just a few days. For example:
24
Sleep disturbances may decrease within three
to four days.
Energy begins to return within four to seven
days.
Mood, concentration, ability to focus, and
interest in lifes activities begin to improve
within seven to 10 days.
The following SSRIs are used for the treatment
of depression. All are now available in generic
form.
2,13,19,24,27
Citalopram (Celexa).
Escitalopram (Lexapro).
Fluoxetine (Prozac, Prozac Weekly, Sarafem).
Paroxetine (Paxil, Paxil CR, Pexeva).
Sertraline (Zoloft).
Fluvoxamine (Luvox).
Some SSRIs are available in the extended-release
or controlled-release forms. These are usually
designated with the letters XR, CR or SR. Such
drugs enable a controlled release of medication
throughout the day or even for a week at a time
with just a single dose. Pharmacy technicians
should use caution when interpreting orders
for these medications to prevent medication
errors, because there are often controlled release
and instant release formulations of the same
medications.
2,13
Side effects commonly associated with SSRIs
include:
2,9,13,19
Fatigue.
Headache.
Tremor.
Dizziness.
Insomnia.
Dry mouth.
Nausea.
Diarrhea.
Agitation or restlessness.
Reduced libido.
Diffculty reaching orgasm.
Erectile dysfunction.
Rash.
Diaphoresis.
Weight gain.
Drowsiness.
Vaginal dryness.
Edward is a 40-year-old biologist who is taking
an SSRI for depression. He is experiencing a
decrease in libido and other adverse sexual side
effects. Edward is considering discontinuing his
medication because of these adverse effects.
Drug alert! Sexual side effects are common in
persons taking SSRIs. More than 50 percent of
patients taking SSRIs report sexual side effects.
5
Patients must be taught about side effects and
when and how to report them. The potential for
side effects, including those of a particularly
personal nature such as sexual side effects, should
be discussed with the patient before prescribing
the medication. The patients physician should
initiate this discussion.
Pharmacists should also be part of the patients
education on SSRI side effects. Patients may not
remember all information discussed with their
prescriber. It is important that other health care
professionals, such as pharmacy staff, ensure that
patients know about side effects and what to do if
they occur.
Drug alert! Fluoxetine (Prozac) causes a
somewhat higher rate of mild agitation and loss
of weight compared to other SSRIs, but produces
less drowsiness.
24
Pregnancy
Jasmine and her husband are expecting their
frst child in six months. Jasmine has a history
of major depression. She is beginning to exhibit
signs and symptoms of another depressive
episode. She, her husband and her health care
provider need to discuss the risks and the benefts
of antidepressant therapy, a conversation that
ideally should have taken place before Jasmine
became pregnant!
Some antidepressants may place the fetus at risk
during pregnancy or the drugs may pass to the
baby during breastfeeding. Paroxetine (Paxil) in
particular seems to be linked to an increased risk
of birth defects, including cardiac and respiratory
problems.
13
Women of childbearing age should
be counseled about the risks of taking an
antidepressant while pregnant. Women who are
considering becoming pregnant should discuss
depression treatment options with their doctor or
pharmacist before becoming pregnant.
Drug interactions
Mr. Wallace is a 75-year-old retired banker. He
is taking aspirin on a daily basis. He is also
taking an SSRI for depression. His daughter
fnds him unconscious, and he is rushed to the
hospital. He is found to have extensive internal
bleeding, low blood pressure and a signifcantly
increased coagulation time. Drugs that increase
coagulation time, if taken in conjunction with an
SSRI, can cause potentially dangerous increases
in coagulation times.
2,13
There are a number of drugs that can cause
harmful effects if taken in conjunction with
antidepressants. That is why it is so important
to explain to patients that they must inform their
health care providers and other members of the
health care team about all of the medications
they take, including not only prescription drugs,
but also over-the-counter medications, herbal
preparations, vitamins, minerals and even
nutrition supplements and weight-loss products.
Many patients assume that non-prescription
medications and substances such as aspirin,
herbal preparations, weight loss supplements, and
vitamins are not important, so they do not bother
to inform their health care providers that they are
taking them. Patients need to be told that any or
all of these substances may interact negatively
with antidepressants. When taking a patient
history, it is absolutely necessary for health care
Elite Page 11
providers to question patients specifcally about
non-prescription medications, herbs, vitamins,
nutritional supplements, and weight loss
products.
Drug interactions with SSRIs include:
2,13,23,19
Aspirin products.
Non-steroidal anti-infammatory drugs
(NSAIDs).
Coumadin.
Monoamine oxidase inhibitors (MAOIs)
Taking SSRIs and MAOIs within 14 days of each
other can cause neuroleptic malignant syndrome.
This syndrome can be fatal and is characterized
by hyperthermia, rigidity, muscle cramps and
tremors, and instability of the autonomic nervous
system, causing such problems as unstable blood
pressure, agitation, delirium or coma.
2,13,23,19
Serotonin syndrome is also a serious adverse
reaction to antidepressant therapy. It is most
likely to occur when two or more medications
that raise serotonin are used in combination.
This includes the herbal supplement St. Johns
wort, sometimes used in the treatment of
depression. Serotonin syndrome is characterized
by confusion, hallucinations, restlessness, loss
of coordination, vomiting, tachycardia, irregular
heart rates, dilated pupils, fever, changes in blood
pressure, and unconsciousness.
2,13
Length of treatment time and
discontinuing the drug
Recent research suggests that antidepressant drug
therapy should continue for a longer period of
time than the three to six months traditionally
thought to be suffcient for an episode of major
depression. Evidence from studies indicates that
patients who take antidepressants for 18 to 24
months have fewer relapses. And some patients
may need to remain on antidepressant therapy for
years or even a lifetime.
24
Patients must be instructed to take SSRIs as
prescribed. They must not miss several doses and
must not discontinue using the drug abruptly.
When discontinuing SSRIs, the dosage must be
tapered gradually under the supervision of the
prescriber. Abrupt discontinuation can cause
symptoms of withdrawal that include:
2,13,19
Nausea.
Headache.
Dizziness.
Lethargy.
Flu-like symptoms.
Cyclic antidepressants: Tricyclic
antidepressants (TCAs) and tetracyclics
Tricyclic antidepressants (TCAs) and tetracyclics
are among the earliest identifed antidepressants
and are sometimes referred to as cyclic
antidepressants. TCAs were frst used as a
treatment for depression in the mid-1950s.24
Although effective, they have been replaced by
antidepressants that cause fewer side effects.
However, TCAs and tetracyclics may still be
prescribed for patients who do not respond to
other classifcations of antidepressants.15 TCAs
cost less than many other types of antidepressants
because they have been in existence for a longer
period of time and therefore are available in
generic forms.
24
Drug alert! Cyclic antidepressants may also be
used in the treatment of panic disorder, obsessive-
compulsive disorder and eating disorders.
24
These drugs work by increasing the amount of
norepinephrine, serotonin, or both in the central
nervous system.
2
These actions make more
norepinephrine, serotonin, or both available in
the brain, which, in turn, improves the ability of
brain cells to send and receive messages. They
also affect other types of neurotransmitters,
which can cause a number of side effects. Route
of administration varies depending on the specifc
cyclic. Some are available in injectable formats
as well as oral routes.
2,15,19
Drug alert! These kinds of antidepressants
may take from 10 to 14 days to cause symptom
improvement, and it may take six weeks for them
to reach full effect.
24
Cyclics used in the treatment of depression
include:
2,9,15,19
Amitriptyline (Elavil).
Amoxapine (Asendin).
Desipramine (Norpramin).
Doxepin (Sinequan).
Imipramine (Tofranil).
Maprotiline (Ludiomil).
Nortriptyline (Pamelor).
Protriptyline (Vivactil).
Trimipramine (Surmontil).
Drug alert! Some of these drugs are associated
with certain side effects more often than others.
For example, amoxapine (Asendin) can cause
extrapyramidal symptoms such as extreme
restlessness, tremors, and involuntary movements
as well as neuroleptic malignant syndrome. It can
also increase appetite, leading to weight gain.
Maprotiline (Ludiomil) is associated with a risk
for seizures (especially in patients who consume
large amounts of alcohol), severe constipation
and retention of urine.
24
Side effects of cyclics can vary depending on the
specifc medication. Common side effects can
include:
2,15,19
Photophobia.
Dry mouth.
Drowsiness.
Blurred vision.
Constipation.
Urinary retention.
Dizziness.
Delayed orgasm.
Decreased sex drive.
Tachycardia.
Confusion.
Hypotension.
Increased appetite and weight gain.
Fatigue.
Headache.
Nausea.
Seizures.
Drug alert! Remember that side effects of cyclics,
as with any medication, must be discussed with
the patient before initiating therapy. Health care
providers need to provide enough information
so that patients can make informed decisions
about their plan of care. Pharmacy staff must
be prepared to clarify information related to
pharmacology!
Drug alert! Tricyclic antidepressants are often
used to treat insomnia caused by adverse effects
of drowsiness.
27
Pregnancy
There are a number of safety concerns associated
with TCAs and tetracyclics. As with SSRIs,
some cyclics may harm the fetus and may pass
to the baby during breast-feeding. Women of
childbearing age should be counseled about the
risks to the unborn child and to the baby during
breast-feeding before becoming pregnant.
2,15,19
Drug interactions
Adverse drug interactions are also problematic.
Serotonin syndrome is a possibility, as it is with
SSRIs. There are specifc types of drugs that,
if taken in conjunction with cyclics, can cause
specifc, severe problems. These include:
2,15,24,27
CYP2D6 inhibitors.
Barbiturates, alcohol and other CNS
depressants.
Serotonergic medications such as linezolid,
MAO inhibitors, SSRIs, triptans, and St.
Johns wort.
Evening primrose.
Cimetidine.
Clonidine (Catapress).
Quinolones (broad-spectrum antibiotics).
Contraindications
Cyclics are contraindicated in patients who have
severe impairment of hepatic function or those
who are in the acute recovery phase following
a myocardial infarction. They are to be used
with caution in persons who have narrow-angle
glaucoma, enlarged prostate, a history of seizures,
cardiac problems, thyroid problems, diabetes or
impaired liver function.
2,15
Drug alert! There are some environmental
factors that can have an impact on the patient
taking cyclics. Smoking may lower drug levels.
Patients who smoke must be particularly
monitored for lack of drug effectiveness.
Additionally, exposure to the sun may increase
photophobia. Patients should be advised to avoid
excessive exposure to sunlight.
2
Overdose
Marlene is a 55-year-old accountant. After
being diagnosed with major depression, she
was prescribed an SSRI, which did not alleviate
her symptoms. After much discussion with her
physician, Marlene agreed to take Tofranil, a
tricyclic antidepressant. Marlene is very busy
at work and at home and is concerned that
the Tofranil wont work, just like the other
antidepressant. So she decides to take an extra
dose several times a day. After a few days of
taking extra doses, Marlene begins to display
Page 12 Elite
confusion and has a seizure at work. She is taken
to the emergency department of the local hospital
where her blood tests show alarmingly high
levels of Tofranil.
Overdose of tricyclic antidepressants occurs over
a period of several days and may cause serious
consequences. It should be assumed that all
patients are at risk for overdose or for taking their
medications improperly. Occasionally, health care
professionals assume that persons of a certain
age, educational background, or socioeconomic
group follow instructions or comprehend
information more easily than others. This is a
dangerous assumption. All persons, no matter
their age, background, or education, need careful
patient education and follow-up.
Possible consequences of tricyclic overdose
include:
2,16,24
Confusion.
Seizures.
Coma.
Tachycardia.
Cardiovascular toxicity.
Increased refexes.
Agitation.
Hallucinations.
Drug alert! Because of the potential for
serious side effects and because older patients
often have co-existing health problems, cyclic
antidepressants are not favored for use in
geriatric patients. Newer antidepressants
that have fewer side effects and fewer drug
interactions are preferred in this population.
24
As with SSRIs, cyclics should never be abruptly
discontinued. Such abrupt discontinuation can
cause withdrawal symptoms including nausea,
headache, dizziness, lethargy, and fu-like
symptoms.
2,15
Atypical antidepressants
Atypical antidepressants, generally used
when SSRIs are ineffective or when patients
cannot tolerate their side effects, are referred
to as atypical because they do not ft into other
classifcations of antidepressants. Each is unique
and works in different ways with different
side effects and safety concerns. However,
atypical antidepressants are believed to affect
neurotransmitters including dopamine, serotonin,
and norepinephrine.
2,11,19,24
Drug alert! Atypical antidepressants should not
be stopped abruptly. If these drugs are abruptly
discontinued, withdrawal symptoms may occur.
2
Atypical antidepressants used in the treatment of
depression include:
2,11,24
Bupropion (Wellbutrin, Wellbutrin SR,
Wellbutrin XL).
Mirtazapine (Remeron, Remeron SolTab).
Nefazodone (Serzone).
Trazodone (Oleptro).
Bupropion (Wellbutrin, Wellbutrin SR,
Wellbutrin XL)
Bupropions exact action is unknown, but it
is thought to weakly inhibit norepinephrine,
dopamine, and serotonin reuptake. It does
not inhibit MAO, but its noradrenergic or
dopaminergic mechanisms may cause the drugs
anti-depressive effect.
2

Bupropion is believed to be a good choice
for patients who have low energy caused by
depression, but it can exacerbate or cause anxiety
for some people. It is not associated with sexual
side effects or weight gain as often as other
antidepressants.
11
Drug alert! Bupropion is also prescribed as an
aid to smoking cessation treatment.
2
Side effects of bupropion include:
2,11,19
Confusion.
Abnormal dreams.
Insomnia.
Headache.
Tremor.
Sedation.
Agitation.
Dizziness.
Seizures.
Tachycardia.
Arrhythmias.
Blurred vision.
Sore throat.
Rhinitis.
Dry mouth.
Constipation.
Nausea.
Vomiting.
Fluctuations in weight.
Excessive sweating.
Contraindications include:
2
Patients who have taken MAOIs within the
previous 14 days.
Patients with seizure disorders.
Patients with history of eating disorders
(increases the risk of seizures).
Drug alert! Bupropion dosage and frequency
should be reduced in patients who have
impairment of kidney functioning or mild to
moderate liver cirrhosis.
2,19
There are a number of potential adverse drug
interactions with bupropion use. These include:
2
Other antidepressants.
Beta-blockers.
Nicotine replacement agents.
Alcohol.
Drug alert! Excessive sun exposure may increase
the risk of photosensitivity.
2
Drug alert! Bupropion is not approved for use in
children.
2

Mirtazapine (Remeron, Remeron SolTab)
Mirtazapine is believed to act by enhancing
central noradrenergic and serotonergic activity.
Like bupropion, mirtazapine may help to
counter sexual side effects that are caused by
other antidepressants. Because it often causes
drowsiness, it is usually taken at bedtime.
11

Side effects include:
2,11,19
Somnolence.
Dizziness.
Increased appetite.
Weight gain.
Increased cholesterol levels.
Increase or decrease in blood pressure.
Decreased white blood cell count.
Weakness.
Drug interactions include:
2,19
Avoid use within 14 days of MAOI therapy.
CNS depressants, including alcohol.
Mirtazapine should be used with caution
in patients with cardiovascular disease,
cerebrovascular disease, seizure disorders,
hepatic or renal impairment, or history of mania
or hypomania. It is not approved for use in
children.
2
Nefazodone (Serzone)
Nefazodone is thought to work by affecting
neurotransmitters to enhance communication
between brain cells. It may help to decrease
anxiety in addition to alleviating depression. It
is likely to cause drowsiness, but is less likely
to cause sexual side effects than other types of
antidepressants.
11
Drug alert! There have been some reports of
liver failure in some patients taking nefazodone,
so it should be prescribed with caution.
11
11,18
Orthostatic hypotension (Patients should be
taught to change positions slowly, especially
when they frst start taking the drug).
Dizziness.
Headache.
Dry mouth.
Blurred vision.
Confusion.
Nausea.
Sleepiness.
Weakness.
Flushing.
Heartburn.
Constipation.
Pain, burning, numbness or tingling in the
hands and feet.
There are many drug interactions with
nefazodone, because it is a potent inhibitor of
liver enzymes that metabolize medications.
When starting a new medication while taking
nefazodone or adding nefazodone to a patients
medication regimen, the pharmacist should be
alerted to discuss drug interactions with the
patient. Among them are:
27
Carbamazepine.
Statin drugs, such as simvastatin, lovastatin,
and atorvastatin.
Benzodiazepines, such as triazolam.
MAOIs and linezolid.
Prostate medications, such as tamsulosin,
alfuzosin, dutasteride.
Eplerenone.
Amiodarone.
Clarithromycin, erythromycin.
Sirolimus, tacrolimus.
Trazodone (Oleptro)
Trazodone is a rather weak antidepressant
thought to work by inhibiting the CNS neuronal
Elite Page 13
uptake of serotonin. It is likely to cause
sleepiness, so is usually taken at bedtime. In
addition to helping to alleviate depression, it
also can help to reduce anxiety. Trazodone is not
approved for use in children.
2,11,19
Drug alert! Trazodone is also prescribed for the
treatment of insomnia and migraine prevention.
2

2,11,19
Drowsiness.
Confusion.
Dizziness.
Orthostatic hypotension.
Dry mouth.
Headache.
Nausea.
Weakness.
Blurred vision.
Arrhythmias.
Fatigue.
Constipation.
Diarrhea.
Drug alert! Trazodone has been linked to a
rare condition called priapism. Priapism is a
persistent, painful erection not associated with
sexual arousal. Patients who have an erection
that lasts longer than four hours should seek
emergency medical treatment.
11
There are a number of potentially dangerous drug
interactions with trazodone. These include:
2,19
Other antidepressants.
Anti-hypertensives.
Digoxin and phenytoin.
MAOIs.
Warfarin.
Herbs, such as ginkgo biloba and St. Johns
wort.
Alcohol.
Monoamine oxidase inhibitors (MAOIs)
Raymond has been dealing with major depression
for nearly a year. SSRIs were not helpful in
reducing his symptoms, nor were some of the
cyclic antidepressants. He and his physician
discussed other options, including the use of
MAOIs. As part of the discussion, Raymonds
physician asked him questions about his diet.
Raymond explained that he enjoyed a glass
or two of beer every night and loved all types
of cheeses, especially cheddar. Raymond also
has slightly elevated blood pressure. Raymonds
physician knows that Raymond will either have
to signifcantly change his diet or try medications
other than MAOIs.
MAOIs were the frst type of antidepressant
drug developed, and although effective, they,
like TCAs, have been replaced by other types
of antidepressants that are safer and cause
fewer side effects.
8
One of the major concerns
with MAOIs is that they generally necessitate
dietary restrictions. If these drugs are taken
in conjunction with a diet high in tyramine-
containing foods, life-threatening hypertension
may occur.
2,12
However, MAOIs may still be
prescribed if the patient does not respond to other
types of antidepressants.
The scenario at the beginning of this section
shows that a patient like Raymond is at risk for
complications and adverse effects because of
two main reasons: his diet and the fact that he
is already hypertensive. The integration of all
body systems makes prescribing antidepressants
something of a challenge for prescriber and
patient alike. It also makes the need for careful
monitoring an absolute necessity.
Monoamine oxidase is an enzyme that helps
to remove the neurotransmitters serotonin,
dopamine and norepinephrine from the brain.
MAOIs work by inhibiting this removal, making
more of these neurotransmitters available in the
brain and enhancing brain cell communication.
However, MAOIs also affect other
neurotransmitters in the brain and in the digestive
system, causing signifcant side effects.
12
MAOIs used in the treatment of depression
include:
2,12,19
Isocarboxazid (Marplan).
Phenelzine (Nardil).
Tranylcypromine (Parnate).
Drug alert! Selegiline (Emsam, Zelapar)
is available as a transdermal patch and is
used for the treatment of Parkinsons disease.
Administering the drug via the patch may cause
fewer side effects compared to the oral form of
the drug.
2,12,19
Side effects of MAOIs include:
2,12,19
Headache.
Insomnia.
Dizziness.
Nausea.
Arrhythmias.
Low blood pressure.
Diarrhea.
Dry mouth.
Changes in sense of taste.
Nervousness.
Muscle aches.
Weight gain.
Diffculty urinating.
Paresthesia.
Reduced sexual desire.
Diffculty reaching orgasm.
Pregnancy
There are signifcant safety concerns associated
with the use of MAOIs. As with other
classifcations of antidepressants, MAOIs may
place a fetus at risk and may pass to the infant
during breast-feeding. Women of childbearing
age should be counseled about the risks to the
unborn child and to the baby during breast-
feeding prior to becoming pregnant.
2,12,19
Drug and food interactions
MAOIs should never be taken in conjunction
with other types of antidepressants or with St.
Johns wort, an herb, because of the risk of
dangerously high levels of serotonin (serotonin
syndrome). Ginseng in combination with
MAOIs may cause headache, tremors, or mania.
Concurrent use should be avoided.
2,19
Patients taking MAOIs must restrict foods that
contain high levels of tyramine, which is an
amino acid found naturally in the body and in
certain foods and helps in the regulation of blood
pressure. Interaction of tyramine and MAOIs
can cause dangerous, even life-threatening
hypertension.
12

Hypertensive crisis is the most serious side effect
of the interaction between tyramine-containing
foods and MAOIs. Symptoms include:
24
Occipital headache (headache at the lower
back of the head).
Nausea.
Vomiting.
Chills.
Sweating.
Restlessness.
Stiff neck.
Fever.
Dilated pupils.
The crisis can be so severe that it can eventually
cause brain hemorrhage and death.
24
Tyramine is found in especially large amounts
in aged foods or foods that contain signifcant
amounts of yeast. Foods that have moderate to
large amounts of tyramine include:
3
All tap beers.
Bottled or canned beer, including
nonalcoholic beer.
Aged cheeses such as cheddar, brie, and
camembert.
Aged, smoked, fermented, and pickled meats
such as pepperoni, salami, and meat jerky.
Banana peel.
Breads or crackers that contain cheese.
Soy products.
Pickled herring.
Smoked fsh.
Red and white wine.
Yeast extracts.
Patients should be provided with a list of foods
that are high in tyramine and that should be
avoided. A dietary consult is recommended to
help patients modify their diets to reduce their
intake of tyramine.
Drug alert! As with any antidepressant, MAOIs
should never be discontinued abruptly.
2
Serotonin and norepinephrine reuptake
inhibitors (SNRIs)
SNRIs work by increasing brain concentrations
of the neurotransmitters serotonin and
norepinephrine. They are also used to treat
other mental health issues, such as anxiety,
fbromyalgia, and pain from diabetic peripheral
neuropathy.
2,13,19
SNRIs used to treat depression include:
2,13,19
Duloxetine (Cymbalta).
Venlafaxine (Effexor, Effexor XR).
Desvenlafaxine (Pristiq).
Venlafaxine is available in an immediate-release
form (requiring two or three doses daily) and in
an extended-release form administered once a
day.
13
Page 14 Elite
Drug alert! Cymbalta can also be used to treat
neuropathic pain.
27
SNRI side effects include:
2,13,19
Nausea (especially with duloxetine).
Dizziness.
Fatigue.
Headache.
Dry mouth.
Insomnia.
Constipation.
Sweating.
Elevated blood pressure (especially with
venlafaxine).
Tachycardia.
Decreased sexual desire.
Blurred or double vision.
Arrhythmias.
Diffculty urinating.
Drug interactions include:
2
MAOIs.
Alcohol.
SSRIs.
Pregnancy
There are signifcant safety concerns associated
with the use of SNRIs. As with other
classifcations of antidepressants, SNRIs may
place a fetus at risk and may pass to the infant
during breast-feeding. SNRIs should not be used
in the third trimester of pregnancy. Women of
childbearing age should be counseled about the
potential benefts versus risks to the child before
becoming pregnant.
27
Antidepressant use in bipolar disorder
Sarah is a social worker who has recently
relocated from a large metropolitan area to a
rural community. She was diagnosed with bipolar
disorder three years ago and has responded
well to treatment with lithium. Shortly after
relocating, Sarah begins to suffer the symptoms
of a depressive episode. She is tired of taking
lithium and decides to visit one of the two
doctors in her new home, a tiny rural town.
Unfortunately, Sarah decides not to tell the
doctor about her bipolar disorder and only
tells him about her depression, attributing it to
her recent divorce. The physician prescribes
an antidepressant. After a few weeks, Sarahs
depression lifts and she immediately swings into
a serious manic phase, something that has not
happened for over a year.
The use of antidepressants in bipolar disorder
patients remains controversial. If antidepressants
are used, it is generally recommended that a
mood stabilizer be taken as well to prevent
or reduce the risk for switching to manic or
hypomanic phases or developing rapid cycling
symptoms. In fact, research results from a large
National Institute of Mental Health (NIMH)
study showed that adding an antidepressant
to a mood stabilizer is no more effective in
treating the depression than using only a mood
stabilizer.
26
If antidepressants are prescribed for a patient
with bipolar disorder, pharmacy staff and other
members of the health care team should check
to see whether the patient is also taking a mood
stabilizer. If not, a discussion with the prescriber
is indicated to help prevent the patient from
experiencing rapid cycling between moods of
depression and mania.
Herbal medicines
Samantha owns and operates a successful health
club. She is very interested in being physically ft
and is a big supporter of homeopathic medicine.
Samantha has a family history of depression and
has suffered from repeated episodes of major
depression herself. She has been taking an SSRI
for nearly a year with signifcant reduction in
symptoms. However, Samantha has decided
to add the herbal preparation ginkgo to her
antidepressant regimen without informing her
physician. After several weeks of taking both her
prescribed antidepressant and ginkgo, Samantha
notices that she has begun to bruise easily and
bleeds for quite some time after experiencing
simple injuries such as paper cuts. Samantha
does not know that she is experiencing a drug
interaction caused by ginkgo.
The need to ask patients about their use of herbal
supplements is growing more urgent every day.
It is believed that nearly half of all health care
consumers in the United States are taking some
type of herbal supplement, either alone or with
prescription medications.
22
Yet many of these
patients have no idea that herbs can cause adverse
effects.
A number of herbal medicines have been used
in the treatment of depression. Patients should
be cautioned that if they are consulting with
herbal medicine practitioners, they MUST inform
their other health care providers of any herbal
supplements they are taking. Some patients
believe that herbs are natural and therefore
do not have adverse side effects or interactions
with medicines. It is imperative that patients
understand that herbs have the potential to
cause dangerous, even fatal, side effects and
interactions with other drugs as well as affect lab
tests.
Drug alert! Herbs should ideally be prescribed
by an herbal practitioner who is well versed and
qualifed in herbal medicine and who works as a
partner with the patient, his or her physician, and
other members of the patients health care team.
All health care providers should ask their patients
whether they are taking any type of herbal
supplement to avoid dangerous side effects and
drug interactions.
Some of the herbal medicines used to treat
depression are described below. Note that a
discussion of these herbs is not to be taken as an
endorsement for their use.
St. Johns wort
St. Johns wort is available in capsule, tablet,
tincture, sublingual capsule, and cream formats.
It should not be used during pregnancy and
lactation, nor should it be given to children. Side
effects include dizziness, insomnia, restlessness,
fatigue, constipation, abdominal cramps,
photosensitivity, rash and hypersensitivity.
20,22,25
The following drug interactions are associated
with St. Johns Wort:
20,22,25
MAOIs.
Antidepressants.
ACE inhibitors, loop diuretics, and thiazide
diuretics.
Alcohol.
Amphetamines.
NSAIDs.
Persons taking St. Johns wort should limit
foods high in tyramine. These include aged
cheeses, beer, smoked and pickled meats, and soy
products.
3,22
St. Johns wort may cause increased growth
hormone, decreased serum prolactin, serum iron
and digoxin.
22
Ginkgo
Ginkgo is a tree native to China and Japan but
is now also found in Europe and the United
States. Its medicinal parts are the dried or fresh
leaves and seeds separated from the outer layer.
It is available in capsule, fuid extract, tablets,
and tincture forms. It should not be used during
pregnancy or lactation, nor should it be given to
children. It is also contraindicated in persons with
coagulation or platelet disorders, hemophilia or
seizures. Side effects include headache, anxiety,
restlessness, nausea, vomiting, anorexia, diarrhea,
fatulence and rash.
22,25
The following drug interactions are associated
with ginkgo.
22,25
St. Johns wort.
MAOIs.
Anticoagulants and platelet inhibitors.
Anticonvulsants.
Buspirone and fuoxetine.
Trazadone.
Ginkgo may increase bleeding time and decrease
platelet activity, thereby leading to increased risk
of bleeding.
22
Khat
Khat is a tree found in Africa and on the Arabian
Peninsula, and the raw leaves of the tree are used
to make herbal medicine. It is ingested by eating
the raw leaves followed by fuids.
22,25
Khat should not be used during pregnancy and
lactation, nor should it be given to children.
Its use is contraindicated in persons who have
compromised renal, cardiac or hepatic systems.
22
22,25
Tachycardia.
Arrhythmias.
Elevated blood pressure.
Pulmonary edema.
Circulatory collapse.
Restlessness.
Insomnia.
Headache.
Hallucinations.
Elite Page 15
Hyperthermia.
Diaphoresis.
Nausea or vomiting.
Anorexia.
Constipation.
Abdominal pain and spasms.
Cerebral hemorrhage.
Decreased sperm count.
Decreased libido.
Khat may affect the action of the following
drugs:
22,25
Amphetamines.
Anti-arrhythmia agents.
Antihistamines.
Anti-hypertensives.
Beta-blockers.
Calcium channel blockers.
Cardiac glycosides.
Decongestants.
MAOIs.
Mugwort
Mugwort is a perennial plant found in North
America and Asia.
20,22
The plants medicinal parts
are the root and aboveground parts, especially
the dried tips of the branch. Mugworts taste is
described as pleasant and tangy.
20
This herbal
medicine is also used to treat anxiety, menstrual
disorders, constipation, colic and diarrhea.
22
In
China, mugwort is used as a treatment for ulcers
and burns.
20
Mugwort is available as a tincture
and as a tea.
20,22
Mugwort is a uterine stimulant and should
not be used during pregnancy. It should not
be given to children, nor should women
who are breastfeeding ingest it. Mugwort is
contraindicated in patients who have bleeding
disorders.
22
Side effects include nausea, vomiting, anorexia
and contact dermatitis. If patients who are also
taking anticoagulants take mugwort, an increased
risk for bleeding may occur. Concurrent use is
contraindicated.
22
Use of alcohol and other central nervous system
(CNS) depressants may increase sedative
effects.
25
Lemon balm
Lemon balm is a perennial plant found in the
eastern Mediterranean region, western Asia, and
is cultivated in Europe and North America.
20,22

The medicinal parts of the plant are the oil
extracted by the process of distillation, dried
leaves, fresh leaves and the whole plant.
20
It is
available as an extract, infusion, a cream, herb
powder and in capsule form.
20,22
Lemon balm is used to treat agitation, sleep
disturbances, migraines, attention defcit disorder,
hypertension, gastric problems and bronchial
conditions as well as depression. Its use as an
antiviral and antimicrobial is being investigated.
20
Lemon balm is contraindicated in:
22
Pregnancy.
Breastfeeding.
Persons who have hypothyroidism.
Persons who have glaucoma.
Side effects include nausea and anorexia.
22
There are several potential drug interactions,
including:
22,25
CNS depressants.
Iron salts.
Thyroid hormone.
Herbs such as catnip, chamomile, kava,
valerian and other herbs that have sedative
effects.
Yerba mate
Yerba mate is an evergreen plant found in South
America. The medicinal parts of the plant are
its dried leaves.
22
In addition to depression,
yerba mate has been used to treat fatigue,
gastrointestinal problems, kidney stones,
bladder stones, urinary tract infections, arthritis,
constipation, and as an appetite suppressant and
diuretic.
22,25
In China, yerba mate is administered
parenterally to treat hypertension.
22
Yerba mate is available as a tincture, a tea, and an
extract.
22,25
Yerba mate should not be used during pregnancy
or breastfeeding, nor should it be given to
children. Patients with cardiovascular disease,
gastrointestinal ulcers, chronic liver disease or
kidney disease should not ingest yerba mate.
25
Adverse side effects associated with the use of
yerba mate include:
22,25
Anxiety.
Headache.
Irritability.
Heart palpitations.
Liver damage.
Insomnia.
Restlessness.
Nausea.
Vomiting.
Anorexia.
Yerba mate has also been associated with the
development of certain cancers, such as bladder,
kidney and esophageal malignancies, when used
for long periods of time.
22,25
Patients should be
monitored closely when taking this drug and
should avoid long-term use.
Yerba mate may increase serum glucose and liver
enzyme levels as well as PT and INR.
25
There are a number of drug interactions
associated with the use of yerba mate. These
include:
25
Anticoagulants.
Anti-diabetic medications.
CNS stimulants.
Caffeine or herbs that contain caffeine such
as black tea, cola nut or guarana.
Nutmeg
Nutmeg is a tree that is found in the West Indies
and Sri Lanka.
22
Its medicinal parts are the
seeds.
20,22
Traditional uses for nutmeg include
depression, anxiety, digestive problems, diarrhea,
cramps, fatulence, vomiting, and rheumatism.
It is also used as a spice in food.
20,22
Research
is being conducted to assess nutmegs use as an
anticancer and antimicrobial agent.
22
Medicinal forms of nutmeg include nutmeg oils,
extracts, powders, syrups, butters, and tinctures.
Externally, nutmeg oils are used as linaments.
20
Overdose alert! Ingestion of just one to three
nutmeg nuts(several tablespoons) can lead
to symptoms of overdose. The person may
experience severe thirst, nausea and reddening
and swelling of the face. Changes in level of
consciousness may also occur. These changes
can be fairly minor, such as exhibiting anxiety,
fatigue, or lethargy, or severe and even life-
threatening, such as stupor and hallucinations.
These symptoms can last from two to three days.
Treatment of overdose includes gastric lavage
and installation of activated charcoal.
20
Nutmeg can cause spontaneous abortions, so its
use in pregnancy is contraindicated. It should not
be used during breastfeeding, nor should nutmeg
be given to children as a therapeutic medicine.
Even though it has been used as a treatment for
depression, it should be used with caution in the
presence of major depression.
22
Side effects associated with medicinal use of
nutmeg include:
22
Nausea.
Vomiting.
Anorexia.
Constipation.
Dry mouth.
Spontaneous abortion.
Confusion.
Seizures.
Stupor.
A number of drug interactions are possible with
the medicinal use of nutmeg. These include:
22,25
MAOIs.
Anti-diarrhea medications.
Herbs such as Safrole.
Patient education alert! Patients should be
aware that it is possible to overdose on nutmeg
because it is toxic in signifcant doses, and
toxicity can be fatal. They should be monitored
for adverse central nervous system effects, such
as confusion, lethargy, hallucinations and stupor.
Any such effects should be reported immediately
and medical attention obtained.
22
Managing depression
Patients with depression should always remember
to be open with their doctors and other health
care providers. Patients may feel a certain
stigma associated with their condition, but
should avoid letting this get in the way of proper
disease management. Before going to doctor
appointments, patients should be prepared to
discuss their health care needs, including any
questions they might have thought of since the
last appointment, any symptoms or side effects
they have developed, any changes in their home
lives, such as moving or changing jobs, and any
questions about information they may have found
online or in advertisements.
27
It is incredibly important for patients to carry a
list of the medications, supplements, vitamins,
and herbs they are taking with them, especially
Page 16 Elite
when attending doctor appointments or picking
up new medications from the pharmacy. Many
drugs interact with herbal supplements and over-
the-counter treatments that patients forget to add
to their medication list. The importance of adding
these products to the medication list should be
constantly reinforced with people to prevent
adverse reactions and drug interactions.
27
If patients are not able to manage their treatment
on their own, asking a friend or family member
for assistance in caregiving may be necessary.
It is incredibly important for patients to include
their loved ones in their mental health treatment.
If family members know that a patient is starting
a new medication, they will be alert to signs
and symptoms that the patient is not improving
or experiencing side effects to the treatment. If
necessary, the caregivers can even go to doctor
appointments with the patient to take notes or
remind the patient of questions that have arisen
since the last appointment.
27
Patient education
Alex is a 40-year-old car salesman who went
through a divorce last year. He is interested in
pursuing a serious relationship with a woman
he has been seeing for several months. He has
been dealing with depression and hopes that
the medication (an SSRI) his physician has
prescribed will help relieve his symptoms. His
physician asks Alex, Do you understand that
this medicine can cause side effects? Alex says
yes, even though he doesnt really remember
what the doctor told him. He is anxious to have
the prescription flled and get ready for what he
believes will be an important date that evening.
As he picks up his medication, Alex confdes to
the pharmacist, who is also a good friend, that
he hopes to initiate a sexual relationship with
the woman he has been dating. The pharmacist
initiates a discussion, in private, about the
side effects of SSRIs, which include sexual
dysfunction. Alex is shocked and refuses to accept
the medication. He returns to his physicians
offce, angry and concerned and demands to
know why No one told me what this drug could
do to me!
Patient education is a crucial part of any
pharmacology intervention. Pharmacy technicians
must recognize gaps in patient and family
education, report these gaps to the pharmacist,
and facilitate the provision of necessary
education. In the case of Alex, the physician did
not adequately assess the patients knowledge of
the medication prescribed. The result is an angry,
concerned patient, and a physician who must deal
with that anger and concern.
Teaching alert! It is imperative to measure
the patients and families comprehension of
patient education. They should never simply be
asked, Do you understand how to take your
medications? or other questions that can be
answered only with a yes or no response. To
assess patient and family knowledge, they should
be asked open-ended questions to explain how
they will take the drugs, list side effects and so
on.
To measure comprehension, patients and families
should be able to:
State the name of the drugs they are taking.
Be able to read the name of the drugs being
taken and remove them from any containers
that house the drugs.
Recognize visually as well as in writing the
drugs being taken.
Identify the dose and route of the drugs being
taken.
Explain the side effects of the drugs and
when to seek medical intervention for such
side effects.
State what to do if a dose is missed or if
overdose occurs.
Explain safety precautions associated with
the drugs being taken. For example, if a
drug lowers blood pressure, do patients and
families know that it is necessary to change
position slowly?
Explain how to take drugs, for example, with
food, on an empty stomach, and so on.
Explain the importance of keeping follow-up
appointments with health care providers or of
having specifc blood tests performed.
Note that the preceding statements all begin with
a verb that can be measured. For example, the
patient or family members must explain or state
or identify something. They must demonstrate
their knowledge in ways that can be observed or
heard. If patients are asked, Do you know the
side effects your medication can cause? they
may just say yes to avoid admitting they dont
know or to save time. But asking patients to state
the medications side effects requires that they
must verbally demonstrate their knowledge of
such side effects.
Be sure to provide patients and families with
information about their medications that they can
take with them. Patients and families should be
given written patient education materials written
in terms that the average patient and family
members can understand and in a language that
they can understand.
All pharmacy staff members must keep up-
to-date on new medications, changes to safety
recommendations by the FDA, and removal of
drugs from the market. The FDA (www.fda.
org) provides free updates via e-mail and text
on research fndings and information about
drugs. Several well-known, reputable health care
organizations (e.g., www.mayoclinic.com) offer
extensive information about various diseases and
their treatments written for patients, families and
health care professionals.
Jason has been taking an antidepressant for
several months. His wife has been reading
everything she can fnd about depression
and medications used for its treatment.
While surfng the Internet, she reads several
articles posted by people who claim that they
suffered irreversible brain damage from
antidepressants. She and Jason decide that he
should stop taking his medication immediately.
Jason soon experiences severe withdrawal
symptoms and must be hospitalized to deal with
their effects. When asked why he didnt discuss
his concerns with his physician or pharmacist,
Jason replies that he thought anything published
on the Internet was reliable information!
Teaching alert! Ask what websites patients and
families are using to obtain information about
their health and about their treatment regimen.
Make sure that they are acquiring information
from reputable sources. Patients may assume that
everything they read on the Internet is accurate
and trustworthy. They need to be directed to
reliable health care websites.
Emphasize the importance of telling health care
providers what medications they are taking,
including herbs, vitamins, dietary supplements
and over-the-counter medications. Explain that
any or all of such agents can have serious, even
life-threatening interactions.
Pharmacy staff must also be prepared to deal
with patients who are not only concerned and
anxious but who may be angry as well. They may
be angry because they are ill, because they must
take medication, because their family and friends
do not understand that depression is an illness,
because the disorder is affecting their ability to
work or maintain interpersonal relationships, or
for many other reasons.
Patients are usually angry because of a reason
that has nothing to do with the pharmacy
staff members. But they may take out their
frustrations on pharmacy staff and other
members of the health care team. Here are some
suggestions when dealing with angry patients or
family members.
Do not take their anger personally, even
though this might be diffcult to do.
Stay calm. Being angry will only escalate the
patients (or family members) anger.
Speak in a normal tone of voice. Raising your
voice will only make the situation worse.
Whenever possible, try to resolve the
problem in a private setting. Avoid a public
scene that other patients can overhear and
that will probably upset people who have
nothing to do with the problem.
Stay at eye level with the patient or family
member. Maintain eye contact.
Encourage the person or persons who are
angry to sit down. The act of sitting down
in a private setting and speaking in a calm
tone of voice may be enough to defuse the
situation.
Show that you are interested in helping the
patient and family resolve their issues.
Acknowledge that the patient or family
member is upset. For example, suppose the
patient has had to wait a long time for a
prescription to be flled. Apologize for the
inconvenience and explain how you hope to
avoid long waits in the future. Dont offer
excuses or become defensive. Sometimes
simply acknowledging their concerns and
expressing regret for whatever is upsetting
them can defuse an unpleasant situation.
Elite Page 17
Address the patient or family by name. Using
their names indicates interest. Be respectful.
Address them as Mr., Mrs., or Ms. Do not
use frst names unless invited to do so.
Never address a patient or family member as
honey, dear, sweetheart, or other name
that can be interpreted as condescending.
Showing respect is very important when
attempting to defuse an unpleasant situation.
Be aware of your body language. Do not
clench your fsts or cross your arms. Avoid
frowning, rolling your eyes, or other facial
expressions that indicate anger, disgust, or
amusement. Never give the impression that
you are laughing at the patient or family
member.
Be objective. Do not judge patients by their
lifestyle, age or socioeconomic status.
Assess whether the patient or family member
has the potential to become violent. Watch for
agitated body movements or body language
that indicates the potential for violence, such
as clenched fsts.
Have a plan for maintaining your own safety.
Although this does not happen frequently,
patients or family members can become
physically violent. If speaking privately
with a patient, do not allow him or her to
get between you and the door or other exit.
Always be sure you can get away from
a potentially dangerous situation. Never
meet privately with someone unless there
is another staff member nearby. You need
to be able to summon help quickly. Before
meeting privately with patients or families,
be sure to tell a colleague where you will be
and with whom you will be meeting. Know
the policies and procedures for dealing with
potentially dangerous situations and for
dealing with angry patients. Preparing for
these kinds of situations in advance will help
you to cope with them more easily.
Finally, remember that patients and their
families are equal partners with their health
care providers. They must be encouraged to
express their concerns and to ask questions. Their
knowledge of their treatment plan, particularly
their medication regimen, must be objectively
assessed. Compliance is not possible unless and
until patients and families believe in and are
compliant with the treatment plan that has been
prescribed.
References
1. Centers Diseases Control and Prevention (CDC). (2011). CDC report: Mental illness
surveillance among adults in the United States. Retrieved December 30, 2011 from
www.cdc.gov/mental1healthsurveillance/fact_sheet.html.
2. Comerford, K. C. (2012). Nursing 2012 drug handbook. Philadelphia: Wolters Kluwer/
Lippincott Williams & Wilkins.
3. Drugs.com. (2011). Low tyramine diet. Retrieved January 4, 2012 from http://www.
drugs.com/cg/low-tyramine-diet.html.
4. Durkin, M. T. (Ed.). (2013). Professional guide to diseases (10th ed.). Philadelphia:
Wolters Kluwer/Lippincott Williams & Wilkins.
5. Harvard Medical School. (2011). Antidepressants and tamoxifen. Retrieved December
31, 2011 from http://www.health.harvard.edu/newsletters/Harvard_Mental_Health_
Letter/2010/June/antidepressants-and-tamoxifen.
6. Health Communities. (2011). The biology of depression and anxiety. Retrieved April
3, 2012 from http://www.healthcommunities.com/depression/biology-of-depression-
and-anxiety_jhmwp.shtml
7. Health Communities. (2011). Causes and risk factors for depression. Retrieved April 3,
2012 from www.healthcommunities.com/depression/causes.shtml.
8. Health Communities. (2011). Depression incidence and prevalence. Retrieved
December 31, 2011 from www.healthcommunities.com/depression/incidence-
prevalence.shtml.
9. Health Communities. (2011). Depression medications. Retrieved December 15, 2011
from www.healthcommunities.com/depression/antidepressant.shtml.
10. Health Communities. (2011). Types of depression. Retrieved April 3, 2012 from
www.healthcommunities.com/depression/types.shtml.
11. Mayo Clinic. (2010). Atypical antidepressants. Retrieved December 31, 2011 from
www.mayoclinic.com/health/Atypical-antidepressants/MY01561/METHOD=print.
12. Mayo Clinic. (2010). Monoamine oxidase inhibitors (MAOIs). Retrieved December
31, 2011 from www.mayoclinic.com/health/maois/MH00072/METHOD=print.
13. Mayo Clinic. (2010). Selective serotonin reuptake inhibitors (SSRIs).
Retrieved December 31, 2011 from www.mayoclinic.com/health/ssris/MH00066/
METHOD=print.
14. Mayo Clinic. (2010). Serotonin and norepinephrine reuptake inhibitors (SNRIs).
Retrieved January 7, 2012 from www.mayoclinic.com/health/antidepressants/
MH00067/METHOD=print.
15. Mayo Clinic. (2010). Tricyclic antidepressants and tetracyclic antidepressants.
Retrieved December 31, 2011 from www.mayoclinic.com/health/antidepressants/
MH00071/METHOD=print.
16. Medscape. (2010). Toxicity, medication-induced dystonic reactions. Retrieved
January 14, 2012 from http://emedicine.medscape.com/article/814632-overview.
17. National Institute of Mental Health. (2009). Co-occurrence of depression with
other illnesses. Retrieved January 10, 2012 from http://www.nimh.nih.gov/health/
publications/men-and-depression/co-occurrence-of-depression-with-other-illnesses.
shtml
18. National Institute of Mental Health. (2011). Nefazodone. Retrieved January 5, 2012
from www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000956/?report=printable.
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20. PDR. (2007). PDR for herbal medicines (4th ed.). Montvale, NJ: Thomson.
21. Robinson, J. M. (Clinical Director). Professional guide to signs & symptoms (6th
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NY: McGraw-Hill; 2011.
ANTIDEPRESSANT DRUG THERAPY
FOR PHARMACY PROFESSIONALS
www.elitecme.com.
6. There are several different types of
depressive episodes. Which of the
following is among them?
a. Single depressive episode.
b. Recurrent depression.
c. Seasonal affective disorder.
d. All of the above.
7. Which of the following is considered to be
a possible cause of depression?
a. Use of anti-parkinsonian medications.
b. A diet containing too much sugar.
c. Use of aspirin.
d. A diet high in protein.
8. Which of the following medications is not
an SSRI?
a. Fluoxetine.
b. Duloxetine.
c. Paroxetine
d. Fluvoxamine.
9. Which of the following antidepressants is
not an atypical antidepressant?
a. Trazodone.
b. Nefazodone.
c. Duloxetine.
d. Bupropion.
10. Which of the following herbs is commonly
used for the treatment of depression?
a. Cayenne.
b. St. Johns wort.
c. Soy.
d. Melatonin.
RPTAZ03ADE13
Page 18 Elite
CHAPTER 3
CALCULATION OF DOSAGES AND
SOLUTION RATES USING RATIO AND
PROPORTION
(4 CONTACT HOURS)
By Alene Burke, MSN, RN, received her Master
of Science in Nursing Administration and Nursing
Education from Adelphi University, and has completed
coursework towards a Ph. D. Alene has been
consulting on the development, design, and production
of competency and educational activities since 1998.
She has authored several publications including
resource books and textbook chapters. She has
provided continuing education for numerous medical
professionals, including pharmacists.
Author Disclosure: Alene Burke and Elite Professional
Education do not have any actual or potential conficts
of interest in relation to this lesson.
0761-9999-13-279-H04-T
Activity Type: Application-based
Initial Release Date: August 12, 2013
Expiration Date: August 12, 2015
666-9053. This lesson is $17.00.
education credit.
Learning objectives
At the conclusion of this course, you should be
able to accurately:
! Perform basic arithmetic calculations.
! Relate the equivalents for a household
measurement system.
! Relate the equivalents for the apothecaries
system.
! Relate the equivalents for the metric system.
! Convert among the systems of measurement.
! Accurately calculate oral, parenteral
and intravenous dosages using ratio and
proportion, including for pediatric dosages
that are based on body weight.
Introduction
Pharmacy technologists work in a wide variety
of settings. The roles and responsibilities of
pharmacology technologists vary somewhat in
different settings and even among those that are
similar.
For example, pharmacy technicians may not
do intravenous admixtures in a community
pharmacy department within a major retail
store, but they may have to accurately add
Did you also notice that the numerators in the
three above improper fractions are more than
the denominators? For example, the 5/3 fraction
represents that there are 3 parts in the whole and
you have 5 parts, which is more than the whole,
or greater than 1.
When the numerator and the denominator are
identical, the fraction is equal to 1. For example,
the fraction 6/6 is equal to 1 and the fraction
987/987 is equal to 1. The numerators and
denominators are identical. Of the 6 parts in the
whole, you have all 6 parts; and of the 987 parts
in the whole, you have all 987 parts, therefore it
is a whole, or 1.
Reducing fractions
Both proper and improper fractions can be
reduced to their lowest common denominator.
Reducing fractions make them easier to work
with.
Reducing fractions involves recognizing a
number that can be evenly divided into both the
numerator and denominator. For example, if
the fraction is 3/9, both the numerator (3) and
the denominator (9) can be evenly divided by
3 without anything left over. When you reduce
3/9, you divide the numerator of 3 by 3, and then
you divide the denominator of 9 by 3, as shown
below:
3 3 = 1
9 3 = 3
Therefore, 3/9 = 1/3
Likewise, you can reduce 66/124, as shown
below:
66 2 = 33
124 2 = 62
Therefore, 66/124=33/62
Now, lets try to reduce these fractions. (Hint:
If there is no common denominator, the fraction
cannot be reduced.)
6/9 Both 6 and 9 can be reduced by 3 to
the fraction 2/3.
16/24 Both 16 and 24 can be reduced by 8
to the faction 2/3.
16/9 This fraction cannot be reduced or
made smaller because there is no
number you can divide into both
16 and 9. There is no common
denominator.
By reducing fractions to their common
denominators, you are really determining their
equal fractions. So 6/9 is equal or equivalent to
2/3 in the example above.
Practice problems: Reducing fractions
Reduce the following fractions to their lowest
common denominators:
1. 16/22 = _____
2. 7/77 = _____
3. 8/23 = _____
4. 12/67 = _____
5. 34/88 = _____
6. 88/880 = _____
Now check your answers.
medications to intravenous solutions in an acute
care hospital or medical center. Furthermore,
some acute care hospitals and medical centers
may only allow licensed pharmacists to prepare
intravenous admixtures; others may allow
pharmacy technicians to perform this role under
the supervision of a licensed pharmacist.
Despite these differences, most pharmacy
technicians must be thoroughly prepared and able
to calculate accurate dosages of all types. There is
no room for error; these dosages must be accurate
and without any errors. Even the smallest error
can lead to a serious medication error. This
course will provide you with the knowledge,
skills and abilities to provide safe, accurate
pharmaceutical patient care and drug dosages
without any errors whatsoever.
Basic arithmetic calculations
An underlying presumption for this course is that
you, the learner, have the basic ability to add,
subtract, multiply and divide numbers. If you feel
that you are not fully competent in terms of these
basic arithmetic functions, it is recommended that
you review and study these functions at this time
and before continuing with this course.
In addition to the ability to perform basic
addition, subtraction, multiplication and
division, you should also be able to perform
basic mathematical calculations using fractions,
mixed numbers and decimals. These mathematic
calculations are discussed and described below.
Fractions
There are two types of fractions:
Proper fractions.
Improper fractions.
Proper fractions are less than 1; improper
fractions are more than 1.
Fractions are indicated by a slash or a divide
line, with a number above and number below the
slash or divide line. The number above the slash
or divide line is called the numerator, and the
number below is referred to as the denominator.
Here are some examples of proper fractions. All
of these fractions are less than 1:
1/2 or : In both fgures, 1 is the numerator
and 2 is the denominator.
2/5 or : In both fgures, 2 is the numerator
and 5 is the denominator.
88/345 or : In both fgures, 88 is the
numerator and 345 is the denominator.
Here are some examples of improper fractions.
All of these fractions are more than 1:
5/3: 5 is the numerator and 3 is the
denominator.
denominator.
denominator.
Did you notice that the numerators in the above
proper fractions are less than the denominators?
All of these fractions are less than 1. For
example, the 2/5 fraction represents that there are
5 parts in the whole and you have only 2 of the 5
parts, less than a whole, or 1.
2
1
5
2
345
88
Elite Page 19
Now, lets convert these mixed numbers into
improper fractions:
6 5/8 = = 53/8 .
Next, check your answer by changing the
improper fraction back to the original mixed
number:
53/8 means 53 divided by 8, which equals 6
5/8.
Practice problems: Mixed numbers
Now, perform these practice problems by
converting the mixed numbers into improper
fractions and then converting these improper
fractions back to the mixed number.
1. 3 4/7 = _____
2. 5 3/8 = _____
3. 14 6/9 = _____
4. 11 2/11 = _____
The solution for each of these practice problems
is shown below:
1. 3 4/7 = = = 25/7
To check this improper fraction, do this: 25/7
(or 25 divided by 7) = 3 4/7.
2. 5 3/8 = = = 43/8
To check this improper fraction, do this: 43/8
(or 43 divided by 8) = 5 3/8.
3. 14 6/9 = = = 132/9
To check this improper fraction, do this:
132/9 (or 132 divided by 9) = 14 6/9.
4. 11 2/11 = = = 123/11
To check this improper fraction, do this:
123/11 (or 123 divided by 11) = 11 2/11.
Decimals
Decimals are another way of expressing a
proper fraction, an improper fraction and mixed
numbers. Deci means 10, and all decimals are
based on the system of tens or the power of
ten. For example, 0.7 is 7 tenths; 8.13 is 8 and
13 hundredths; likewise, 9.546 is 9 and 546
thousandths.
Below is a chart that shows the meaning of
decimal places:
Decimal
places
Meaning Example and
equivalent
1 Tenths 2.3 = 2 and 3 tenths
2 Hundredths 21.98 = 21 and 98
hundredths
3 Thousandths 0.985 = 985
thousandths
4 Ten-
thousandths
2.4444 = 2
and 4,444 ten-
thousandths
5 Hundred-
thousandths
0.77777 =
77,777 hundred-
thousandths
When the decimal point is preceded with a zero,
the number is less than 1; when there is a whole
number before the decimal point, the number
is more than one or equal to one. Numbers
with decimal points are readily converted into
fractions and mixed numbers. For example:
Answers to practice problems: Reducing
fractions
1. 16/22 = 8/11
The 16 and the 22 can both be divided by 2,
therefore, 16 divided by 2 is 8; 22 divided by
2 is 11. Thus, 8/11 is the answer because 8
and 11 cannot be divided evenly by any other
number.
2. 7/77 = 1/11
therefore, 7 divided by 7 is 1; 77 divided by 7
is 11. Thus, 1/11 is the answer because 7 and
77 cannot be evenly divided by any number
other than 7.
3. 8/23 cannot be reduced.
4. 12/67 also cannot be reduced. Only 1 can be
evenly divided into 12 and 67.
5. 34/88 = 17/44
therefore, 34 divided by 2 is 17; 88 divided
by 2 is 44. Thus, 17/44 is the answer because
17 and 44 cannot be evenly divided by any
other number.
6. 88/880 = 1/10
The 88 and the 880 can both be divided by
88, therefore, 88 divided by 88 is 1; 880
divided by 88 is 10.
Mixed numbers
Mixed numbers are a mix of a whole number and
a fraction. For example, 2 1/2 teaspoons and 4 5/8
tablespoons are both mixed numbers. As you can
see from these two examples, all mixed numbers
are more than 1 or more than a whole. For
example, 2 1/2 teaspoons is 2 whole teaspoons
plus 1/2 a teaspoon.
You have to convert all mixed numbers into
improper fractions, which are also more than 1,
before you can perform any calculations with
them. For example, you have to convert 2 1/2
into 5/2, and you have to convert 4 5/8 into 37/8
as fully discussed below.
To perform this calculation, you:
Multiply the denominator by the whole
number.
Then add the numerator to it.
Then divide this number by the denominator.
2 1/2 = = 5/2
In this example, you multiply the denominator of
2 by the whole number of 2 and then add 1, the
numerator of the fraction. Finally, you divide by
the denominator of 2. So, 2 x 2 = 4; 4 + 1 = 5,
and 5 is then placed over the denominator of 2.
As you may see, the improper fraction of 5/2 can
be converted back to a mixed number as shown
below:
5/2 means 5 divided by 2, which equals 2 1/2.
When you turn mixed numbers back into
improper fractions, you can easily check your
mathematical calculation. If your original
calculation gives you 5/2 and you convert this
back to a mixed number, you should see the
original mixed number.
2.3 = 2 and 3 tenths or 2 3/10.
21.98 = 21 and 98 hundredths or
21 98/(100 ).
Decimal numbers are often rounded off when
pharmaceutical calculations are done. When you
have to round off to the nearest hundredth, you
must look at the next number, or thousandth, and
determine whether it is less than 5, equal to 5 or
more than 5.
For example, if the number in the third place after
the decimal, or thousandths place, is an 8, which
is greater than 5, then you round up the number
in the hundredths place by 1. For example,
45.758 is rounded to the nearest hundredth, or
45.76, because the 8 in the thousandths place is
greater than 5. Likewise, if you are rounding off
to the nearest tenth, you look at the number in
the hundredths place to see whether it is greater
than 5. For example, 6.2346 is rounded off to 6.2
because the 3 in the hundredths place is not more
than 5 or equal to 5.
Now, here are some numbers rounded off to the
nearest tenth. Remember, if the hundredths place,
or second number after the decimal, is 5 or more,
the tenths place is increased by 1, and if the
second number after the decimal is less than 5,
the number in the tenths place remains the same.
In these examples, the bolded number in the
hundredths place (2 numbers after the decimal)
is the one that determines whether the number
in the tenths place (the frst number after the
decimal) moves up 1 or remains the same.
3.44 = 3.4
0.78 = 0.8
0.66 = 0.7
0.99 = 1.0
Here are some numbers rounded off to the nearest
hundredth. Again, the bold numbers are the ones
you have to scrutinize to see whether they are
equal to or less than 5, or greater than 5:
3.456 = 3.46
0.754 = 0.75
0.766 = 0.77
1.999 = 2.00
Practice problems: Rounding off decimals
Round off these numbers to the nearest tenth:
1. 4.5678 = _____
2. 12.087 = _____
3. 88.999 = _____
4. 65.123 = _____
5. 26.656 = _____
Answers to practice problems: Rounding
decimals to the nearest tenth
1. 4.5678 is rounded to 4.6 because the number
in the hundredths place is more than 5.
in the hundredths place is less than 5.
in the hundredths place is 5.
2
2 x 2 +1
8
8 x 6 + 5
7
7 x 3 + 4
7
21 + 4
8
8 x 5 + 3
9
14 x 9 + 6
11
121 + 2
8
40 + 3
9
126 + 6
=
11 x 11 + 2
11
Page 20 Elite
Now, round off these numbers to the nearest
hundredth:
1. 4.5678 = _____
2. 12.087 = _____
3. 88.999 = _____
4. 65.123 = _____
5. 26.656 = _____
Answers to practice problems: Rounding
decimals to the nearest hundredth
in the thousandths place is more than 5.
2. 12.087 is rounded to 12.09 because the
number in the thousandths place is more than
5.
number in the thousandths place is more than
5.
number in the thousandths place is 5.
number in the thousandths place is 5 or more.
The household system of measurement
In pharmacology, there are three systems
of measurement. These systems include the
household measurement system, the metric
system and the apothecary system. The household
measurement system is more often used in the
outpatient setting, like a local pharmacy, rather
than within medical settings. It is the least precise
and exact of all the measurement systems.
The household system is the system that most
of us use at home, usually in the kitchen. The
household system uses measurements for drops,
teaspoons, tablespoons, ounces, cups, pints, quart,
gallons, and pounds.
There are some similarities between the
household measurements and the apothecary
system. For example, a fuid ounce is the same
in both systems. There are some differences
as well, for example, the ounce that is used to
determine weight is different in these systems. In
the apothecary system, there are 12 ounces in a
pound, whereas 16 ounces makes up a household
system pound.
The household measurement system table
displays household units of measurement and
their approximate equivalents.
The household measurement system
Unit of
measurement
Approximate equivalents
1 teaspoon 3 teaspoons = 1 tablespoon
60 drops
5 mL
1 tablespoon 1 tablespoon = 3 teaspoons
15 mL
1 liquid ounce 1 fuid ounce = 2 tablespoons
30 mL
1 ounce
(weight)
16 ounces = 1 pound
30 g
1 cup 8 ounces
16 tablespoons
240 mL
1 pint 2 cups
480 mL
1 quart 2 pints
4 cups
1 liter
1 gallon 4 quarts
8 pints
3,785 mL
1 pound 16 ounces
480 g
The apothecaries system of measurement
The apothecary system of measurement is one
of the oldest forms of measurement. In the
1970s, the United States practically abolished
this system, but some physicians still use it, so it
is important to be educated on this system even
though it is rare and less commonly used than the
metric system.
In the apothecary system, the basic measurement
of weight is the grain (gr). The other forms of
measurement for weight in this system include
the scruple, the dram, the ounce and the pound.
For volume, the basic unit of measurement is the
minim (m). This is equivalent to the amount of
water in a drop, which is also equal to 1 grain.
Other measurements for volume include a fuid
dram, a fuid ounce, a pint, a quart and a gallon.
Lowercase Roman numerals are used in this
system of measurement, and these Roman
numerals follow the unit of measurement. For
example, 4 grains is written as 4 iv.
The apothecary system table shows the weight
and volume apothecary system measures and
their approximate equivalents.
The apothecary system
Weight Approximate equivalents Volume Approximate equivalents
1 grain
(gr)
Weight of a grain of wheat
60 mg
1 minim Quantity of water in a drop
or 1 grain
1 scruple 20 grains (gr xx) 1 fuid dram 60 minims
1 dram 3 scruples 1 fuid
ounce
8 fuid drams
1 ounce 8 drams 1 pint 16 fuid ounces
1 pound 12 ounces 1 quart 2 pints
1 gallon 4 quarts
The metric system of measurement
The metric system is the most commonly used
measurement system in pharmacology. It is used
all over the world. Understanding the metric
system and being able to convert between units
of measurements is critical when working in the
pharmacy.
Volume measurements are liters (L), cubic
milliliters (ml) and cubic centimeters (cc). This
systems volume measurements are used for oral
medications, such as cough syrups, and with
parenteral drug dosages used intramuscularly,
subcutaneously and intravenously.
The units of weight in this system include
kilograms (kg), grams (g), milligrams (mg) and
micrograms (mcg).
The metric system table displays the metric
length, volume and weight measurements and
their equivalents.
The metric system
Length Equivalent Volume Equivalent Weight Equivalent
1 millimeter
(mm)
0.001 meter 1 milliliter
(mL)
0.001 liter 1 milligram
(mg)
0.001 gram (g)
1 centimeter
(cm)
0.01 meter 1 centiliter (cl) 0.01 liter 1 centigram
(cg)
0.001 gram (g)
1 decimeter
(dm)
0.1 meter 1 deciliter (dl) 0.1 liter 1 decigram
(dm)
0.1 gram (g)
1 kilometer
(km)
1,000 meters 1 kiloliter (kl) 1,000 liters 1 kilogram (kg) 1,000 grams (g)
1,000
milliliters (mL)
1 liter 1 kilogram (kg) 2.2 pounds (lbs)
1 milliliter
(mL)
cubic
centimeter
(cc)
1 pound (lb) 43,592
milligrams (kg)
10 millimeters
(mm)
1 centimeter
(cm)
10 milliliters
(mL)
1 centiliter
(cl)
1 pound (lb) 45,359.237
centigrams (cm)
10 centimeters
(cm)
1 decimeter
(dm)
10 centiliters
(cl)
1 deciliter
(dl)
1 pound (lb) 4,535.9237
decigrams (dg)
10,000
decimeters
(dm)
1 kilometer
(km)
10,000
deciliters (dc)
1 kiloliter
(kl)
Elite Page 21
Converting between measurement
systems
Pharmacy technicians often have to convert from
one measurement system to another. For example,
if the doctor has ordered a medication in terms of
grains (gr) and you have the medication but it is
measured in terms of milligrams (mg), you will
have to mathematically convert the grains into
milligrams.
The table below shows conversion equivalents
among the metric, apothecary and household
measurement systems.
Conversions among the systems of
measurement
Metric Apothecary Household
1 milliliter 15-16 minims 15-16 drops
4-5 milliliters 1 fuid dram 1 teaspoon or
60 drops
15-16
milliliters
4 fuid drams 1 tablespoon
or 3-4
teaspoons
30 milliliters 8 fuid drams
or 1 fuid
ounce
2 tablespoons
240-250
milliliters
8 fuid ounces
or 1/2 pint
1 glass or cup
500 milliliters 1 pint 2 glasses or 2
cups
1 liter 32 fuid
ounces or 1
quart
4 glasses,
4 cups or 1
quart
1 milligram 1/60 grain
60 milligrams 1 grain
300-325
milligrams
5 grains
1 gram 15-16 grains
1 kilogram 2.2 pounds
The 10 most frequently used conversions
The most frequently used conversions are
shown below. It is suggested that you memorize
these. If at any point you are not sure of a
conversion factor, look it up. Do NOT under any
circumstances dispense or prepare a medication
that you are not certain about. Accuracy is
required.
1 Kg = 1,000 g
1 Kg = 2.2 lbs
1 L = 1,000 mL
1 g = 1,000 mg
1 mg = 1,000 mcg
1 gr = 60 mg
1 oz. = 30 g or 30 mL
1 tsp = 5 mL
1 lb = 454 g
1 tbsp = 15 mL
Ratio and proportion
The ratio and proportion method is the
most popular method to calculate dosages
and solutions. Other methods include the
memorization of a number of rules, which are
often forgotten, and a simple, no-rules method
called dimensional analysis. The remainder
of this course will teach you about ratio and
proportion and ways to precisely calculate all
types of dosages.
A ratio is two or more pairs of numbers that are
compared in terms of size, weight or volume. For
example, the ratio of women less than 20 years of
age compared to those over 20 years of age who
attend a specifc college can be 6 to 1. This means
that there are six times as many women less than
20 years old as there are women over 20 years of
age.
There are a couple of different ways that ratios
can be written. These different ways are listed
below.
1/6
1:6
1 to 6
When comparing ratios, they should be written
as fractions. The fractions must be equal. If they
are not equal, they are not considered a ratio.
For example, the ratios 2/8 and 4/16 are equal
and equivalent. To prove they are equal, simply
write down the ratios and cross multiply both the
numerators and the denominators. The answer for
both of these would be the same. For example,
you can cross multiply the 2 and 16 as well as the
4 and 8 with this ratio of 2/8 and 4/16:
2 x 16 = 32
8 x 4 = 32
Because both multiplication calculations yielded
32, this is a ratio.
On the other hand, 2/5 and 8/11 do not make a
ratio because 8 x 5 (40) is not equal to 11 x 2
(22).
Calculating proportions
Proportions are used to calculate how one part
is equal to another part or to the whole. For
these calculations, you cross multiply the known
numbers and then divide this product of the
multiplication by the remaining number to get the
unknown number.
For example:
2/4 = ?/12
Method 1:
12 x 2 = 24
24/4 or 24 4 = 6
Answer: 6 is the unknown, so the fnal
equation will look like this:
2/4 = 6/12
Method 2:
1. 2/4 = ?/12
You can reduce the frst fraction by 2
to make the calculation a little easier.
2. 1/2 = ?/12
12 x 1 = 12
12 2 = 6
Answer: 6 is the unknown, so the fnal
equation will look like this:
2/4 = 6/12
Practice problems: Ratio and proportion
1. 5/15 = 20/?
2. 8/? = 7/22
3. 66/36 = ?/12
4. ?/6 = 43/53
5. 4/3 = 9/?
Answers to practice problems: Ratio and
proportion
1. 5/15 = 20/?
15 x 20 = 300; 300 5 = 60
2. 8/? = 7/22
8 x 22 = 176; 176 7 = 25.14
3. 66/36 = ?/12
66 x 12 = 792; 792 36 = 22
4. ?/6 = 43/53
43 x 6 = 258; 258 53 = 4.87
5. 4/3 = 9/?
9 x 3 = 27; 27 divided by 4 = 6.75
Calculating oral dosages with ratio and
proportion
Oral dosages are calculated in a number of
different ways, including using ratio and
proportion. Using the same techniques that
you just learned for ratio and proportions, you
will now learn how to accurately calculate oral
dosages using this method.
Doctors order: 500 mg of medication once a
day
Medication label: 1 tablet = 250 mg
How many tablets should be administered daily?
In this problem, you have to determine how many
tablets the patient will take if the doctor orders
500 mg a day and the tablets are manufactured in
tablets of 250 mg.
This problem can be set up and calculated like
this.
500 mg: X tablets = 250 mg: 1 tablet
or
=
Then you cross multiply: 500 mg x 1 = 500
mg
250 X = 500 mg
X = 500 mg/250 mg
500 250 = 2 tablets
Answer: 2 tablets
Now, if you were working in a medical center
that uses unit dosage, you would deliver two
tablets of this medication each day. If, however,
the doctor wants the outpatient to take 500 mg
per day for 30 days, you would dispense 60
tablets, as shown below.
Daily dosage = 2 tablets x 30 days = 60 tablets
Doctors order: Tetracycline syrup 300 mg po
once daily
Medication label: Tetracycline syrup 50 mg/mL
How many mL should be administered per day?
For this oral dosage problem, you have to fnd
out how many mL of tetracycline the patient will
get when the doctor has ordered 300 mg and the
syrup has 50 mg/ml.
x
500 mg
1 tablet
250 mg
Page 22 Elite
This problem is set up and calculated as shown
below.
300 mg: X mL = 50 mg: 1 mL
or
=
50 X = 300
X = 300/50
300 50 = 6 mL
Answer: 6 mL
And if, for example, the doctor had ordered
this dosage two times a day for 10 days for an
outpatient, in addition to the above calculation,
you also would perform the following
calculation:
6 mL (per dose) x 2 (times per day) = 12 mL
each day. This client would have a total of 12
mL per day in two equal doses of 6 mL each.
Because the doctor ordered 300 mg po
two times a day for 10 days, you would
additionally perform the below calculation:
12 mL per day x 10 days = 120 mL
You would dispense 120 mL of the
medication with instructions that the client
take 6 mL two times per day for 10 days.
Practice problems: Oral dosages using
ratio and proportion
Problem 1:
Doctors order: Gantrisin 500 mg po
Medication label: Gantrisin 1 g/tablet
How many tablets should be administered?
Problem 2:
Doctors order: Trimethoprin 2.5 mg/kg po
Patients weight: 40 kg
Medication label: Trimethoprin 80 mg/tablet
Problem 3:
Doctors order: Nystatin 6 mg/kg po
Patients weight: 230 lbs
Medication label: Nystatin 200 mg/tablet
Answers to practice problems: Oral
dosages using ratio and proportion
Problem 1:
Doctors order: 500 mg po
Medication label: Gantrisin 1 g/tablet
This is a two-step problem. The frst step
calculates the number of grams equal to the 500
mg dose. This is done because the drug label is
written in grams, and the doctors order is written
in mg. What you do know, however, is that there
are 1,000 mg in 1 g.
Below is how you set this up to fnd out how
many grams are equal to 500 mg.
=
When you cross multiply, you will get 1000 X =
500 x 1, and then you set this up:
X = 500/1000
X = 1/2 g
1/2 g = 0.50 g is equal to 500 mg
The next step is to calculate what dose, in grams,
should be administered.
x= 500/1000 = 1/2
Answer: 1/2 tablet
Problem 2:
Doctors order: Trimethoprin 2.5 mg/kg po
Patients weight: 40 kg
Medication label: Trimethoprin 80 mg/tablet
This is another two-part question. First you
calculate the number of milligrams to be
administered based on the weight of the patient.
You know that the doctor ordered 2.5 mg/kg po
and the patient weighs 40 kg.
=
X = 40 2.5
X = 100 mg will be given
In the next step, you have to calculate the number
of tablets that the patient will be given based
on the patients weight and that the doctor has
ordered 2.5 mg for each kg of body weight.
=
80 X = 100
X = 100/80
100 80 = 1.25 tablets
Answer: 11/4 tablets
Problem 3:
Doctors order: Nystatin 6 mg/kg po
Medication label: Nystatin 200 mg/tablet
This problem has three steps. In the frst step, you
calculate the patients weight in kilograms. There
are 2.2 pounds in each kilogram, so this problem
is set up as below.
=
2.2 X = 230 kg
X = 230/2.2
230 2.2 = 104.55 kg
Round off the patients weight to 105 kg because
the number in the tenths place is 5 or more.
You then have to calculate the dosage of the
medication, based on the patients weight of 105
kg.
=
105 6 = 630 mg
In the last step, you have to calculate how many
tablets will be administered when each tablet is
200 milligrams.
=
200 X = 630
X = 630/200
630 200 = 3.1 tablets; rounded off to 3 tablets
Answer: 3 tablets
Calculating intramuscular and
subcutaneous dosages with ratio and
proportion
The process for calculating intramuscular and
subcutaneous dosages is practically identical to
that of calculating oral dosages using ratio and
proportion.
Doctors order: Meperidine 20 mg IM q4h prn
for pain
Medication label: Meperidine 60 mg/mL
How many mL or cc will you give?
Using ratio and proportion, this problem is set up
and solved as shown below.
=
60 X = 20 x 1
x = 20/60
20 60 = 0.33 mL, which rounded off to the
nearest tenth is 0.3 mL
Answer: 0.3 mL
Here is another example:
Doctors order: Amikacin 10 mg/kg IM tid
Medication label: 250 mg/1 mL
How many milliliters need to be administered?
For the frst step, you calculate the patients
weight in kilograms.
=
2.2 X = 230
X = 230/2.2
230 2.2 = 104.54 kg
The patients weight can be rounded off to 105 kg
because the tenths place (5) is equal to or more
than 5.
The next step is to fgure out how many milliliters
the patient will get in each of the three doses per
day.
=
1 X = 105 10
105 10 = 1050 mg
In the fnal step, you will need to calculate how
many milliliters are needed to administer the
ordered number of milligrams.
=
250 X = 1050 = 1050/250
1050 250 = 4.2 mL
Answer: 4.2 mL
Now, lets do this one together:
Doctors order: Heparin 2,500 units
subcutaneously
Medication label: 5,000 units/mL
How many milliliters will be administered for
this patient?
=
5,000 X = 2,500
X = 2,500/5,000
2,500 5,000 = 0.5
Answer: 0.5 mL
And one more:
Doctors order: Ticarcillin 300 mg IM
Medication label: Ticarcillin reconstituted with
2 mL of sterile water to yield 1 g of Ticarcillin in
2.6 mL of solution
How many milliliters need to be administered?
x mL
300 mg
1 mL
50 mg
g
500 mg
x mg
40 kg
x tablet
100 mg
1 tablet
80 mg
x kg
230 lbs
1 kg
2.2 lbs
x mg
105 kg
6 mg
1 kg
630 mg
x tablets
200 mg
1 tablet
x
20 mg
1 mL
60 mg
Xkg
239 lbs
1 kg
2.2 lbs
1 kg
10 mg
105 kg
X mg
1 mL
250 mg
XmL
1050 mg
2,500 Units
X mL
1 g
1000 mg
2.5 mg
1 kg
5,000 Units
1 mL
Elite Page 23
For these kinds of problems, the information
about how much sterile water is added for
reconstitution is not used in the calculation. What
is, however, used in the calculation is how many
grams are yielded after the sterile water has been
added. In this case, 1 g is contained in every 2.6
mL. You will be doing these types of calculations
when you are adding medications to intravenous
fuids (admixtures), particularly when you are
doing IV piggybacks in an acute care setting.
The frst step is to fnd out how many g there are
in 300 mg:
=
1000 X = 300
X = 300/1000
300 1000 = 0.3 g
The next step is to determine how many mL will
be administered when the ordered dosage is 300
mg or 0.3 g
=
X = 0.3 2.6
0.3 2.6 = 0.78 mL
Rounded off to: 0.8 mL
Answer: 0.8 mL
Practice problems: Intramuscular and
subcutaneous dosages using ratio and
proportion
Problem 1:
Doctors order: Neomycin 40 mg/kg/day IM in
3 divided doses
Medication label: Neomycin 250 mg/mL
How many milliliters are needed for each of the
three daily doses?
Problem 2:
Doctors order: Heparin 2000 units
subcutaneously
Medication label: 3500 units/mL
How many milliliters would this patient need to
have administered?
Problem 3:
Doctors order: Ceruroxime 250 mg IM
Medication label: The addition of 3.2 mL of
sterile water yields a suspension of 750 mg in 4.2
mL
How many milliliters need to be administered in
this case?
Problem 4:
Doctors order: Cephalothin 200 mg IM
Medication label: The addition of 4 mL of sterile
water yields 0.5 g in 2.2 mL of suspension
How many milliliters would you administer in
this situation?
Problem 5:
3 doses
Medication label: Neomycin in 500 mg/mL
How many milliliters should be given?
Problem 6:
Doctors order: 250,000 Units of Ampicillin
Medication Label: 50,000 units/mL
How many milliliters should be administered to
this patient?
Answers to the practice problems:
Intramuscular and subcutaneous dosages
using ratio and proportion
Problem 1:
3 divided doses
Medication label: Neomycin 250 mg/mL
How many milliliters are needed for each of the
three daily doses?
This, again, is a three-step problem. In the frst
step, you will fnd out the patients weight in
kilograms.
=
2.2 X = 160
X = 160/2.2
160 2.2 = 72.72 kg
Patients weight can be rounded off to 73 kg.
In step two, you will fgure out how many mg
there are in the total daily dosage.
=
X = 73 40
73 40 = 2920 mg
The medication label states that there are 250 mg/
mL, so you will now calculate how many mL the
patient will get.
250 X = 2920
X = 2920/250
2920 250 = 11.68 mL
The fnal step for this problem is to calculate
each dosage based on a total of 11.68 mL in three
divided doses.
11.68 3 = 3.89
The dosage can be rounded to 3.9 mL per dose,
and the patient will get this dose three times per
day
Answer: 3.9 mL per dose
Problem 2:
Doctors order: Heparin 2000 units
subcutaneously
Medication label: 3500 units/mL
How many milliliters would this patient need to
have administered?
=
3500 X = 2000
X = 2000/3500
2000 3500 = 0.57 mL
This dosage can be rounded off to 0.60 mL or 0.6
mL
Answer: 0.6 mL
Problem 3:
Doctors order: Ceruroxime 250 mg IM
Medication label: The addition of 3.2 mL of
sterile water yields a suspension of 750 mg in 4.2
mL
How many milliliters should be dispensed?
=
750 X = 250 4.2
750 X = 1050
X = 1050/750
1050 750 = 1.4 mL
Answer: 1.4 mL
Problem 4:
Doctors order: Cephalothin 200 mg IM
Medication label: The addition of 4 mL of sterile
water yields 0.5 g in 2.2 mL of suspension
How many milliliters would you administer in
this situation?
=
1000 X = 200
X = 200/1000
200 1000 = 0.2 g
=
0.5 X = 0.2 2.2 mL
0.5 X = 0.44
X = 0.44/(0.5 )
0.44 0.5 = 0.88, which is rounded off to 0.9 mL
Answer: 0.9 mL
Problem 5:
3 doses
Medication label: Neomycin in 500 mg/mL
How many milliliters should be given?
=
2.2 X = 240
240/2.2
240 2.2 = 109.09 kg
Rounded off to 109 kg
=
X =
109 40 = 4360
=
500 X = 4360
4360/500
4360 500 = 8.72
Rounded off to 8.7 mL
8.7 3 doses = 2.9 mL for each of the three doses
Answer: 2.9 mL
Problem 6:
Doctors order: 250,000 units of Ampicillin
Medication label: 50,000 units/mL
How many milliliters should be administered to
this patient?
=
x g
300 mg
1 g
1000 mg
x mL
0.3 g
2.6 mL
1 g
x kg
160 lbs
1 kg
2.2 lbs
73 kg
x mg
1 kg
40 mg
1 mL
3,500
X mL
2,000 units
4.2 mL
750 mg
X mL
250 mg
1 g
1000 mg
x g
200 mg
2.2 mL
0.5 g
X mL
0.2 g
X g
240 lbs
1 kg
2.2 lbs
x mg
109 kg
40 mg
1 kg
X mL
4360
1 mL
500 mg
X mL
250,000 units
1
109 x 40
X mL
50,000 units
Page 24 Elite
50,000 X = 250,000
X = 250,000/50,000
250,000 50,000 = 5 mL
Answer: 5 mL
Calculating intravenous fow rates with
ratio and proportion
The rule for intravenous fow rates is:
gtts/min = Drip or drip factor
Now, here is how it is set up and calculated:
Doctors order: 0.9% MaCl solution at 50 mL
per hour
How many gtts per minute should be
administered if the tube delivers 20 gtt/mL?
X gtts per min = = 1000/60 = 16.6 gtt
Rounded off to 17 gtt/min
Heres another example:
Doctors order: 500 mL of 5% D 0.45 normal
saline solution to infuse over 3 hours
How many gtt per minute should be given if the
tubing delivers 10 gtt/mL?
X gtts per minute = = 5000/180
5000 180 = 27.7 gtt
Rounded off to 28 gtts per minute
Answer: 28 gtts/min
And now, here is one more:
Doctors order: 15 mL/h of 5% DO 0.45 normal
saline solution
How many gtt per minute should be administered
if the tubing delivers 60 gtt/mL?
X gtts per minute = = 900/60 = 15 gtt
The answer is 15 gtts/min
Practice problems: Intravenous
medications
Problem 1:
Doctors order: 50 mL/h
if the tubing is 60 gtt/mL?
Problem 2:
Problem 3:
Problem 4:
Problem 5:
Answers to the practice problems:
Intravenous medications
Problem 1:
X gtts per min = = 50 gtt (This fraction
was reduced by 60)
Answer: 50 gtt/min
Problem 2:
X gtts per min = = 75/6
75 6 = 12.5, which is rounded off to 13 gtt
because the tenths place is 5 or more
Answer: Rounded to: 13 gtt/min
Problem 3:
= 6000/60
6000 60 = 100 gtt
Answer: 100 gtt/min
Problem 4:
X gtts per min = = 2400/60
2400 60 = 40
Answer: 40 gtt/min
Problem 5:
X gtts per min =
3000 60 = 50
Answer: 50 gtt/min
Conclusion
Pharmacology is a precise science. Medical
errors, including medication errors, can lead to
disastrous results. Medication errors can occur
at any point of this complex multidisciplinary
process.
For example, medication errors can occur as
the result of an incorrect or illegible doctors
order; they can occur during the preparation and
dispensing of the medication; and they can also
occur at the point of administration.
It is the professional responsibility of the
pharmacology technician to insure that NO
errors occur in the preparation and dispensing
of medications. Pharmacy technicians must
check the doctors order for completeness and
correctness; they must validate that the patient
is not allergic to the ordered medication; they
must determine whether there are any drug
interactions; and they must also ensure that
the dosage is accurately prepared, labeled and
dispensed.
This course has provided you with the
knowledge, skills and abilities to prepare and
dispense oral, intramuscular, subcutaneous, and
intravenous medications and solutions in an
accurate and precise manner using the ratio and
proportion method.
As always, check and double-check your
calculations, and consult resources, both human
and written, whenever you are not sure and
certain about the accuracy of your mathematical
calculations.
(Final examination question on next page)
Total number of minutes
Total number of mL
60
50 x 60
60
50 x 20
180
500 x 10
60
15 x 60
60
75 x 10
60
300 x 20
60
40 x 60
60
300 X 10
Elite Page 25
CALCULATION OF DOSAGES AND
SOLUTION RATES USING RATIO AND
PROPORTION
www.elitecme.com.
11. Round 23.6547 to the nearest hundredth.
a. 23.7.
b. 23.66.
c. 2.36.
d. 23.6.
12. Which of the following is equivalent to 1
fuid dram?
a. 60 drops.
b. 2 teaspoons.
c. 10 mL.
d. 20 mL.
13. Select the accurate conversion.
a. 2.2 lbs = 1 Kg.
b. 1 g = 1,000 mg.
c. 60 gr = 1 mg.
d. 1 oz. = 20 mL.
14. The doctor has ordered an oral tablet of a
medication. The order states that the patient
will get 3 mg/kg and the patient weighs
130 pounds. How many total tablets will
be delivered to the nursing unit into the
patients unit dose cassette for 24 hours if
this dosage is given 3 times per day and the
label on the medication states that there are
120 mg per tablet?
a. 4.
b. 4.5.
c. 5.
d. 5.5.
15. The doctor has order 500 mg of an
antibiotic to run over one hour. You have
mixed the antibiotic into 250 mL of
normal saline. How many drops should be
administered per minute if the nurses use a
10 gtt/mL intravenous set?
a. 83 gtt/min.
b. 20 gtt/min.
c. 42 gtt/min.
d. 40 gtt/min.
RPTAZ04CDE13
Page 26 Elite
CHAPTER 4
OVERVIEW OF HERBAL SUPPLEMENTS
(5 CONTACT HOURS)
By Joanne S. Richards, B.S., R.Ph., J.D., RAC. Joanne
graduated from the University of Florida, receiving
both a B.S. in Pharmacology, and a J.D. in Law. Since
then, she has worked as a registered pharmacist in
Kentucky, Florida, and Virginia. She is the Founder
and President of Pharmaceutical Advisory Service, and
has served as an expert witness in regards to pharmacy
law and practice. Joanne also has previous experience
writing content for a variety of purposes.
Author Disclosure: Joanne S. Richards and Elite
0761-9999-13-276-H01-T
666-9053. This lesson is $17.00.
education credit.
Learning objectives
! Defne what an herbal supplement is in the
United States.
! Discuss the extent of use worldwide of herbal
medicine.
! Outline suggested reasons patients do not
disclose their use of herbal supplements to
their health care providers.
! Explain why all health care providers should
incorporate use of herbal supplements
into the patients medical and medication
histories.
! Itemize factors that have an effect on the
quality and therapeutic effcacy of herbal
products.
! Describe the differences between U.S.
regulatory review processes for drugs and
herbal products.
! List the information required and prohibited
by the FDA on herbal supplement labels.
! Generally discuss the issues and problems
associated with scientifc testing and
reporting of research results on herbal
supplements.
! Discuss the historical and current uses for 13
common herbal supplements.
! Discuss side effects and recommended
dosages of 13 common herbal supplements.
botanicals, amino acids, or essential fatty
oils).
Is intended to be taken by mouth as a pill,
capsule, tablet, or liquid.
Is labeled on the front panel as being a
dietary supplement.
Recently, the World Health Organization
estimated that 70-80 percent of people worldwide
rely on herbal medicines for some part of their
primary health care, but only 23-40 percent
of these people tell their physician. Statistics
reveal that the likelihood of consuming herbal
medicines is higher in persons of higher
education and income.
Possible explanations for patients non-disclosure
include:
The belief that natural medicines have no
adverse effects.
The belief that over-the-counter and non-
mainstream medicines are irrelevant to their
doctors overall treatment plan and outcome.
Their concern about a negative reaction from
their practitioner.
The belief that the physician lacks interest or
knowledge about herbals.
Not being asked by their practitioner about
taking herbals.
Their use of herbals is a cultural mainstay of
therapy and they do not even think to disclose
it.
A lack of awareness that herbal medicines
can interact with and alter the therapeutic
effcacy of conventional medications.
To further complicate the issue, detailed
information on herbal supplements is often
outside the general knowledge base of medical
prescribers, either because of limited formal
training or inaccurate or biased information
sources. In addition to physicians and nurses
who dont ask patients about their use of herbal
medicines, some community pharmacists who
on a daily basis are in a key position to assess
interactions with conventional drugs also may
rarely ask patients about their use of herbals.
Thus, because of the prevalent use,
misconceptions, invalid assumptions, and lack
of patient information, it is critical to educate
patients and all those in the health care delivery
chain on the effects that herbal medicine can have
on therapeutic outcomes.
Pharmacology of herbal supplements [30,
75, 82, 101, 109, 127, 162]
In the United States, current good manufacturing
practices (cGMPs) applicable to food
manufacturing are the only quality-control
regulations on herbal medicines. The fnal
marketed product, however, is impacted by more
than just satisfying current good manufacturing
practices.
Other factors that infuence the quality and thus
the potential for reliable therapeutic effectiveness
of herbals include:
Identifcation and collection of the botanical
source (e.g. leaf, root, fower).
! Give examples of common herbal
supplements that interfere with medical lab
tests.
supplements that affect blood coagulation and
aggregation.
supplements that interfere with liver
enzymes, liver function, and drugs
metabolized in the liver.
Introduction
There are numerous health risks and
misconceptions associated with herbal
supplements, e.g. potential adverse effects,
drug-drug interactions, lab test interactions,
and dose-to-dose content variability, to name
a few. More often than not, patients and health
care practitioners are unaware of these potential
problems. The physician may even be unaware
that the patient is taking them at all, either
because the patient does not voluntarily disclose
the information or because the health care
practitioner does not ask.
Thus, it is important for those involved in each
step in the continuum of patient care to be aware
not only of the extent and type of problems they
may encounter when patients consume herbal
medicines, but also to consistently obtain such
information from patients and be able to discuss
the benefts and dangers associated with these
commonly used health aids.
This course provides an overview of herbal
medications and the regulatory process associated
with their manufacture and marketing. With
some of the more frequently used herbals, it
further provides specifc information on safety,
effectiveness, interactions and side effects.
Today, more than ever, patients receive
information from and have access to a variety of
medications, some of which may dramatically
affect the success or failure of the medical
treatment they receive. This lesson emphasizes
how important it is for health care providers to
inquire and for patients to disclose what herbal
medications the patient is taking and to be able
to discuss and explain the potential risks and
benefts associated with them.
Herbal supplement use [14, 32, 34, 35, 64,
82, 100, 122, 147, 160-162, 184]
Compounds extracted from plants, animals,
or microorganisms have been used to treat or
prevent disease for centuries. Examples include
digitalis, reserpine, morphine, penicillin, and
vinca alkaloid anti-cancer drugs. Plants having
medicinal or therapeutic properties, favor, and
scent used to maintain or improve health are
often called herbal products, botanical products,
or phytomedicines.
As defned by Congress in the Dietary
Supplement Health and Education Act of 1994,
a dietary supplement is a product (other than
tobacco) that:
Is intended to supplement the diet.
Contains one or more dietary ingredients
(e.g., vitamins, minerals, herbs or other
Elite Page 27
Isolation, purifcation, and concentration of
one or more active ingredients.
Contaminants, e.g. pesticides and micro-
organisms.
Active ingredient source substitution.
Preparation process of specimens (e.g.,
solutions, desiccation, trituration).
Excipients used.
Storage conditions.
Final product formulation (e.g., solution,
suspension, powder, tablet, capsules).
The impact of these factors is best explained by
understanding how drugs work in our bodies.
Pharmacokinetics, pharmacodynamics, and
bioavailability are terms used to explain this
process.
Pharmacokinetics is the study of the
processes of drug absorption, distribution,
biotransformation, and ultimate elimination
of drugs and their metabolites in the body.
Regardless of route of administration, all drugs
undergo pharmacokinetic processes in one form
or another while in the body. In addition to a
drugs chemical properties, pharmacokinetics
depends on patient-related factors, such as renal
function, genetic makeup, sex, and age. These
factors are often used to predict how a drug will
affect a specifc population.
Pharmacodynamics can be simply explained
as what a drug does to the body. It involves
receptor binding and sensitivity, post-receptor
effects, and chemical interactions. Physiologic
changes caused by disorders, aging, or other
drugs can affect a drugs pharmacodynamics.
The pharmacologic response depends on the
drug binding to its target. The concentration of
the drug at the receptor site infuences the drugs
effect.
Bioavailability refers to the extent and rate at
which the drug or metabolite enters systemic
circulation, thereby accessing the site of action.
Bioavailability of a drug is determined by the
properties of the dosage form, the products
design, and its method of manufacture.
Differences in bioavailability among formulations
of a given drug can have clinical signifcance,
so knowing whether drug formulations are
equivalent is essential.
Chemical equivalence means that the drug
products contain the same active compound and
in the same amount. Inactive ingredients in drug
products may differ. Bioequivalence means that
when the drug is given to the same patient in the
same dosage regimen, equivalent concentrations
of drug in plasma and tissues are achieved.
Therapeutic equivalence means that drug
products, when given to the same patient in the
same dosage regimen, have the same therapeutic
and adverse effects.
Herbal supplement interactions [13, 15, 28,
29, 31, 41, 42, 44, 62, 65, 79, 126, 128, 130]
Herbal supplements can interact with drugs,
other herbs, foods and alcohol, and can affect lab
results. These interactions can affect absorption,
distribution, metabolism, excretion, and interfere
with a drugs ability to reach and exert its effect
on a receptor site. That many herbal products
contain more than one active ingredient further
complicates the process of ascertaining the source
responsible for any unwanted biological event.
Pharmacokinetic interactions
Pharmacokinetic interactions can enhance or
diminish the therapeutic properties of a drug,
thereby evoking an unanticipated, and often
unwanted, clinical response. Examples of this
type of interaction include:
The dose-dependent inhibitory effect
Grapefruit and grapefruit juice affect the liver
enzyme known as CYP3A4 and result in
abnormally high and potentially lethal serum
levels of interacting drugs. Prescription
drugs such as the statins, anti-anxiety drugs,
methadone, and calcium channel blockers
are in this group. For example, goldenseal,
commonly used as a topical antiseptic and
orally for menstrual pain and gastrointestinal
distress, also inhibits CYP3A4, so when
taken with the antibiotic erythromycin, an
abnormally elevated level of the antibiotic
may occur.
The inducer effect
For example, St. Johns wort increases the
speed of degradation and elimination of drugs
transformed by CYP3A4, leading to blood
levels that fall quickly below therapeutic
levels. Drugs interacting in this manner with
St. Johns wort include cyclosporine and
alprazolam.
Pharmacodynamic interactions
Pharmacodynamic interactions result from
actions on molecular targets that mediate
different physiological responses, with results
being an inhibition or potentiation of response.
Examples of pharmacodynamics interactions
include:
St. Johns wort inhibits the serotonin reuptake
when taken in conjunction with other drugs,
such a fuoxetine and paroxetine, that act
similarly, resulting in an abnormally high
level of serotonin at the nerve synapse.
This creates the possibility of serotonin
syndrome, a collection of symptoms
characterized by confusion, restlessness, high
blood pressure, fever, and muscle spasms.
Herbals such as red and sweet clovers when
taken in conjunction with drugs used for their
anti-coagulation or anti-platelet action, such
as warfarin, heparin, aspirin, dipyridamole,
and fbrinolytics, such as alteplase and
reteplase, affect the ability of these drugs
to reliably perform their intended effect as
blood thinners or as an inhibitors of platelet
aggregation.
Herbals and lab test interactions
The Natural Medicines Comprehensive Database
identifes more than 200 different herbs and
supplements that may affect lab test results. The
following is an abbreviated compilation of some
common herbal supplements, some of which are
addressed in detail later on in this lesson:
Supplement Interactions with lab tests
Aloe dried juice Discolors alkaline urine and can interfere with diagnostic tests that
depend on a color change.
May deplete serum potassium concentrations and alter test results.
Bee pollen Bee pollen may increase alkaline phosphatase, alanine aminotransferase,
aspartate aminotransferase, lactate dehydrogenase, total bilirubin,
prothrombin time, and alter test results.
Black cohosh Black cohosh might reduce serum luteinizing hormone concentrations
and alter test results.
Coenzyme Q-10 CoQ-10 doses in excess of 300 mg. per day can elevate SGOT and LDH
concentrations and affect thyroid T4/T8 ratio in normal patients and
some HIV-positive patients.
Evening primrose
oil
Evening primrose oil may interfere with laboratory tests measuring
bleeding time and cholesterol levels, possibly causing false test results.
Green tea The caffeine in green tea can cause false-positive serum urate test
results, can increase urine creatine levels, can cause a slight increase
in urine catecholamines and vanillylmandelic acid levels, resulting in a
false-positive test for pheochromocytoma and neuroblastoma.
Kava Kava can cause liver damage and increase liver enzymes. Liver toxicity
is primarily associated with prolonged use of high doses, but has
been seen with short-term use as well. Liver function tests affected
include aspartate aminotransferase, alanine aminotransferase, alkaline
phosphatase, lactate dehydrogenase, total and conjugated bilirubin, and
gamma-glutamyltransferase.
Lemongrass May elevate levels of serum bilirubin and amylase.
Licorice Licorice can increase serum-hydroxyprogesterone concentrations and
alter test results. Excessive use of licorice can cause hypokalemia and
can decrease serum testosterone concentrations, affecting both lab test
results.
Page 28 Elite
Regulatory approval process comparison
[26, 27, 35, 123, 124]
In the U.S., the drug approval process is strictly
controlled and involves highly detailed safety and
effcacy scrutiny prior to marketing. The process
entails preclinical stages, wherein drugs aimed
at specifc diseases and biological targets are
identifed and tested in vitro and in animals under
controlled conditions to determine their potential
therapeutic beneft.
Once a potential therapeutic beneft is revealed,
an investigational new drug application (IND)
may be submitted to the FDA for review and
approval. The IND application must include the
following information:
Composition of the drug.
Source of the drug.
Manufacturing information.
In vitro and animal studies data.
Plans for proposed human clinical trials.
Background information of the clinical trial
investigators.
If approved, human clinical studies are then
conducted in four phases (I, II, III, and IV).
Phase I is aimed at establishing drug safety,
dosage, and pharmacokinetic properties of the
drug (e.g., half-life and metabolism). These
results are compared with results from the pre-
clinical animal studies.
Phase II studies the effect of the drug on 100-200
volunteer patients having the disease for which
the drug was developed. Toxicological studies in
animals will also continue during this phase to
assess toxicity.
Phase III comprises double-blind or crossover
studies to evaluate drug effcacy in a larger
groups of patients. If the results from Phase III
meet the goals initially established, a new drug
application (NDA) may be submitted to the
FDA containing the data from the human trials.
Upon review of the NDA, the FDA may approve,
disapprove or request further testing of the drug.
If approved, the drug proceeds to market and to
Phase IV.
Phase IV includes post-marketing surveillance
and adverse event reporting.
In the U.S., herbal medications are not considered
drugs, but instead are categorized as dietary
supplements regulated by the Dietary Supplement
Health and Education Act (DSHEA) of 1994.
Whether a product is classifed as a dietary
supplement, conventional food, or drug is based
on its intended use, gleaned from information that
the manufacturer provides on the product label or
in accompanying literature.
Dietary supplements are not approved by the
government for safety and effectiveness before
they are marketed. If the dietary supplement
contains a new ingredient, that ingredient will be
reviewed by FDA before marketing, but only for
safety, not effectiveness.
The quality of a dietary supplement product
cannot be discerned from its label. The degree
of quality control depends on the manufacturer
and others involved in the production process.
In 2007, the FDA issued Good Manufacturing
Practices (GMPs) for dietary supplements, a
set of requirements and expectations by which
dietary supplements must be manufactured,
prepared, and stored to ensure quality.
Manufacturers are now expected to guarantee the
identity, purity, strength, and composition of their
dietary supplements.
The GMPs aim to prevent the inclusion of
the wrong ingredients, to determine ranges
for the quantity of the dietary ingredient, the
possibility of contamination by pesticides,
heavy metals such as lead, and bacteria, and
to prevent improper packaging and labeling of
a product. Manufacturers are also required to
report all serious dietary supplement adverse
events or illnesses to FDA. FDA can take dietary
supplements off the market if they are found to
be unsafe, adulterated, or if the claims on the
products are false and misleading.
Labeling
Unlike drugs, dietary supplements cannot claim
that their product will diagnose, cure, mitigate,
treat, or prevent a disease. A dietary supplement
label may only contain a health claim, nutrient
content claim, or structure/function claim.
Health claims describe a relationship
between a food, food component, or dietary
supplement ingredient that may reduce the
risk of a disease or health-related condition.
Nutrient content claims describe the relative
amount of a nutrient or dietary substance in
a product.
A structure/function claim describes
how a product may affect the organs or
systems of the body, but cannot mention
any specifc disease. FDA approval is not
required for structure/function claims, but
the manufacturer must submit the text of the
claim to FDA within 30 days of marketing
and must include the following disclaimer:
This statement has not been evaluated by
the FDA. This product is not intended to
diagnose, treat, cure, or prevent any disease.
The FDA requires the following information on
all herbal product labels:
Product name, including the word
supplement.
Net quantity of contents.
Name and place of business of manufacturer,
packer, or distributor.
Directions for use.
Serving size.
List of dietary ingredients.
Amount per serving size (by weight).
Percent of Daily Value ( percent DV), if
established.
If the dietary ingredient is a botanical, the
scientifc name of the plant or the common
Melatonin Melatonin supplementation can increase human growth hormone
serum levels, can decrease serum luteinizing hormone levels and can
produce dose-dependent changes in plasma oxytocin and vasopressin
concentrations and alter test results.
Red yeast Due to lovastatin content, red yeast may increase serum levels of liver
transaminase and serum creatine kinase.
Rose hip The vitamin C in rose hip can cause false negative urine results with
methods based on hydrolysis and formation of an indophenol blue
chromagen, can cause a false increase in results of serum tests relying on
color reactions, can cause a false increase in serum test results measured
by Technicon SMA 12/60 or colorimetric methods, can cause falsely
increased serum assay results measured by Ames ARIS method, can
cause a false increase in serum creatinine or urine test results, and can
cause false increases in urine glucose test results measured by copper
reduction methods and false decreases in results measured by glucose
oxidase methods.
Three to six grams of vitamin C daily can cause a true increase in
urinary calcium and a true decrease in urinary sodium and alter test
results. The vitamin C in rose hip can cause a false decrease in LDH
measured by Technicon SMA 12/60 and Abbott 100 methods, may cause
false negative guaiac results to occur with 250 mg or more of vitamin
C per day, can cause falsely decreased theophylline serum assay results
when measured by the ARIS system or Ames Seralyzer photometer,
can cause a true decrease in serum uric acid concentrations, and a false
increase in test results with assays based on other methods.
Senna Senna, due to its anthraquinone content, can discolor urine, interfering
with diagnostic tests that depend on a color change.
Excessive use of senna can cause potassium depletion, reducing serum
potassium concentrations and alter test results.
Soy Soy can inhibit thyroid hormone synthesis, resulting in increased
secretion of thyroid stimulating hormone.
Sweet clover Sweet clover might increase liver enzymes and test results.
Elite Page 29
or usual standardized name and the plant part
name.
If the dietary ingredient is a proprietary blend
(i.e., a blend exclusive to the manufacturer),
the total weight of the blend and the
components of the blend in descending order
by weight.
Non-dietary ingredients, such as fllers,
artifcial colors, sweeteners, favors, or
binders, listed in descending order by weight
using common name or proprietary blend.
Standardization [29, 54, 85, 94, 112, 123]
Standardization is a method of quality control
used to manufacture a consistent product, e.g.
batch-to-batch consistency and identifcation
of chemical markers. Some studies show that
absence of standardization may affect the
reliability of clinical results because of the
variability of active constituents in the dosage
forms used in the trials.
Other studies reveal that chemical compositions
of several commonly used herbals were
reasonably consistent with their labeled
quantities. A greater consistency of composition
marker compounds, however, was observed for
samples purchased over-the-counter than for
those purchased by mail order, with saw palmetto
and St. Johns wort being the least variable, (77-
106 percent and 88-110 percent respectively) and
ginseng and echinacea, the most variable (44-261
percent and 78-173 percent, respectively).
At this time, the National Institute of Standards
and Technology (NIST) in collaboration with the
National Institutes of Health Offce of Dietary
Supplements, the Center for Drug Evaluation
and Research (CDER), and the Center for Food
Safety and Applied Nutrition at the FDA are
developing procedures for the standardization of
active ingredients and chemical contaminants in
dietary supplements and natural health products.
Standardization may result in greater consumer
confdence and acceptance of these alternative
and complimentary therapy options by larger
numbers of conventional health care providers.
Commonly used herbal supplements
Considering the immense number of available
herbals, it is beyond the scope of this lesson to
review them all. Some of the most commonly
used herbal supplements used in the United States
will be reviewed on their use, effectiveness,
safety, interactions, side effects, and dosage.
Black cohosh [125, 129-141]
Background
Black cohosh is a perennial plant, a member of
the buttercup family native to North America.
Preparations are made from its roots and
underground stems. Extracts of black cohosh
are standardized to 26-deoxyactein content, a
member of the group of chemicals known as
saponins. Commercially available preparations
of black cohosh usually contain 1 mg of total
triterpene saponins in each 20-mg dose of extract.
Uses
Historically, black cohosh was used for malaise,
gynecological disorders, kidney disorders,
malaria, rheumatism, sore throat, colds, cough,
constipation, hives, backache, to induce lactation,
rheumatism, as a diuretic, and to bring on
menstruation.
Today, black cohosh is primarily used for hot
fashes and other menopausal symptoms. In
2001, the American College of Obstetricians and
Gynecologists stated that black cohosh may be
helpful in the short term (six months or less) for
women with vasomotor symptoms of menopause.
Effcacy and clinical studies
In a randomized, double-blind, placebo-
controlled trial, 69 breast cancer survivors took
20 mg twice daily of black cohosh for two
months to determine the effect on hot fashes,
excessive sweating, palpitations, headaches,
poor sleep, depression, and irritability. Fifty-
nine subjects were using the anti-estrogen drug
tamoxifen for breast cancer, distributed almost
equally between the treatment and control
groups. The frequency and intensity of hot fashes
and other symptoms decreased in both groups,
with no statistical difference between the groups.
Excessive sweating decreased signifcantly more
in the treatment group than the placebo group.
A randomized, double blind, placebo-controlled
trial in 80 menopausal women compared 8 mg/
day of a black cohosh extract with placebo or
conjugated estrogens (0.625 mg/day). At 12
weeks, Kupperman index and Hamilton anxiety
scale scores were signifcantly lower in the
treated groups than in the placebo group. Daily
hot fashes decreased from 4.9 to 0.7 in the black
cohosh group, 5.2 to 3.2 in the estrogen group,
and 5.1 to 3.1 in the placebo group.
Study results are conficting on whether black
cohosh helps relieve menopausal symptoms. This
could be due to lack of rigor in study design,
short study duration (six months or less), use of
different amounts of black cohosh from different
sources, and use of different outcome measures.
Physiologic effects
Effect on hormone levels
Post-menopausal women generally have lower
levels of estrogen and higher levels of two
other hormones, luteinizing hormone (LH) and
follicle-stimulating hormone (FSH), than do pre-
menopausal women. Three of four studies show
that black cohosh does not affect LH or FSH.
Effect on the vagina
The decrease in estrogen level in post-
menopausal women alters the structure and
activity of vaginal and uterine tissues. Study
results are mixed on whether black cohosh affects
vaginal epithelium.
Effect on the uterus
Menopause is associated with a thinning of the
uterine lining. No human studies have adequately
evaluated the effect of black cohosh on the
uterine lining.
Side effects
Few adverse events have been reported, however,
long-term safety data is not available. Stomach
discomfort, headaches, heaviness in the legs, and
weight problems are the main side effects noted.
Safety, cautions and warnings
Black cohosh is customarily not used for long
periods, e.g., six months or less. A large study
involving postmenopausal women taking
combined estrogen and progestin for an average
of 5.2 years showed a small, but signifcant
increase in the risk of certain diseases. This
study demonstrates the importance of long-term
studies in assessing overall risks. If black cohosh
is estrogenic, long-term use may adversely affect
uterine or breast tissue. No studies have been
published on long-term safety in humans.
Liver damage has been reported in a few
individuals using black cohosh. Despite millions
of uses without apparent adverse health effects,
the U.S. Pharmacopeia (the standards-setting
organization for foods and drugs) advises that
black cohosh products be labeled with the
following cautionary statement: Discontinue use
and consult a health care practitioner if you have
a liver disorder or develop symptoms of liver
trouble, such as abdominal pain, dark urine, or
jaundice.
Black cohosh should only be used under medical
supervision during pregnancy.
Women with breast cancer may want to avoid
black cohosh until its effects on breast tissue are
understood.
Coenzyme Q-10 [125, 176-183]
Background
Coenzyme Q-10 is also referred to as CoQ-10.
It is a vitamin-like substance primarily found in
the heart, liver, kidney, and pancreas. Coenzyme
Q-10 was frst identifed in 1957. Coenzyme
Q-10 is manufactured by fermenting beets and
sugar cane with special strains of yeast. Time
and smoking use up the bodys natural stores of
coenzyme Q-10.
Uses and effcacy
Natural Medicines Comprehensive Database
effectiveness ratings for Coenzyme Q-10 are as
follows:
Likely effective in:
Inherited or acquired disorders that
limit energy production in the cells of
the body (mitochondrial disorders), but
improvement is slow, often exceeding six
months.
Possibly effective for:
Congestive heart failure (CHF) only
when used in combination with other
heart failure medications and treatments.
Patients with chronic heart failure
(CHF) have low plasma concentrations
of coenzyme Q-10, which is associated
with low-density lipoprotein cholesterol.
Studies in the 1990s concluded that
coenzyme Q-10 reduced oxidation of
these low-density lipoproteins. One
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study of 236 patients with CHF found
coenzyme Q-10 to be an independent
predictor of mortality.
The Q-SYMBIO trial is a randomized,
controlled trial involving 422 patients
with chronic heart failure to determine
the benefts of coenzyme Q-10, with an
endpoint including survival. Although
not yet published, after two years of
study, investigators reported at the Heart
Failure 2013 Congress that patients in the
coenzyme Q-10 group had a death rate
half of what the patients in the placebo
group had.
Lowering risk of additional heart
problems in people who have had a
recent heart attack when started within 72
hours of the attack and taken for one year.
Preventing blood vessel complications
and damage from by heart bypass
surgery.
Lowering high blood pressure, alone or
with other medications.
A 2007 meta-analysis of 12 clinical trials
(362 patients) for hypertension concluded
that coenzyme Q-10 has the potential in
hypertensive patients to lower systolic
blood pressure by up to 17 mm and
diastolic blood pressure by up to 10 mm
without signifcant side effects.
Preventing migraine headaches.
Coenzyme Q-10 can decrease the
frequency of headaches by about 30
percent and the number of days with
headache-related nausea by about 45
percent in adults. It can take up to
three months. It is not effective once a
migraine headache has developed.
Slowing the physiological decline in
Parkinsons disease, but does not seem to
improve symptoms in patients with mid-
stage Parkinsons disease.
Enhancing the immune system of HIV/
AIDS patients.
Improving physical performance in some
muscular dystrophy patients.
Possibly ineffective for:
Decreasing high cholesterol or
triglycerides.
Likely ineffective for:
Improving athletic performance.
Treating periodontal disease.
Insuffcient evidence to rate effectiveness
for:
Cyclic vomiting syndrome.
Lowering blood sugar.
Breast cancer.
Improving sperm motility and density in
some infertile men.
Improving exercise tolerance in patients
with chest pain (angina).
Increasing feeling of wellness and
reducing fbromyalgia pain.
Reducing heart wall thickness, shortness
of breath and fatigue in patients with
hypertrophic cardiomyopathy.
Reducing statin-induced myopathic pain.
Preventing pre-eclampsia.
Reducing or preventing warfarin-induced
hair loss.
Safety
Coenzyme Q-10 is likely safe to use in most
adults when taken orally or when applied directly
to the gums. Toxicity is not usually observed
even with high doses of coenzyme Q-10. A daily
dosage up to 3,600 mg was well tolerated by
healthy as well as unhealthy persons.
Coenzyme Q is possibly safe for children, but
should only be used under medical supervision.
Because there is insuffcient information, use
of coenzyme Q-10 should be avoided while
pregnant or breast-feeding.
Side effects
Coenzyme Q-10 is well tolerated in most people.
Common side effects include stomach upset,
loss of appetite, nausea, vomiting, diarrhea, and
allergic skin rashes. Dividing the total daily dose
into smaller increments taken more frequently
can reduce side effects.
Cautions and warnings
Coenzyme Q-10 may lower blood pressure and
may increase the effects of medications used to
lower blood pressure. If the patient has blood
pressure problems, avoid use of coenzyme Q-10
except under medical supervision.
Use of coenzyme Q-10 should be discontinued at
least two weeks before any scheduled surgery.
Interactions
Because coenzyme Q-10 is an antioxidant,
there is some concern that it may decrease the
effectiveness of some cancer drugs. Research is
unclear in this regard.
Coenzyme Q-10 may help the blood clot, thus
may decrease the effectiveness of warfarin and
increase the risk of dangerous clots. If taking
coenzyme Q-10, the dose of warfarin needs to be
closely monitored, and warfarin dosage may need
adjustment.
Red yeast might reduce coenzyme Q-10 levels.
There are no known interactions with foods.
Oral dosage
Dosage ranges from 100-3,600 mg per day in 2-4
divided doses have been studied.
Cranberry [125, 163-167]
Background
Cranberry is a small, evergreen shrub prevalent
throughout North America. The red berries are
used to produce beverages and many other food
products, as well as dietary supplements in the
form of extracts, capsules, or tablets. Cranberry
juice is marketed unsweetened or sweetened with
either sugar or artifcial sweeteners.
Uses and mechanism of action
Cranberry has a long history of use primarily for
preventing urinary tract infections, but also for
neurogenic bladder, to deodorize urine in people
with diffculty controlling urination, to increase
urine fow, to kill germs, to speed skin healing,
and to reduce fever. Some people use cranberry
for type-2 diabetes, chronic fatigue syndrome,
scurvy, pleurisy, and even cancer. More recently,
cranberry has been used as a folk or traditional
remedy for Helicobacter pylori (H. pylori)
infections that can lead to stomach ulcers, or to
prevent dental plaque. Cranberry has also been
reported to have antioxidant and anti-cancer
activity.
It was previously thought that cranberry acidifed
the urine, making it inhospitable for the growth
of bacteria. Current research supports the notion
that some of the chemicals in cranberries keep
bacteria from sticking to the lining of the urinary
tract where they multiply. Cranberry, however,
is not able to release bacteria already adhering
to the lining, which may explain why cranberry
is possibly effective in preventing urinary tract
infections but also possibly ineffective in treating
them.
Cranberry contains signifcant amounts of
salicylic acid that can reduce swelling, prevent
blood clots, and can have antitumor effects.
Effcacy
Preventing urinary tract infections,
particularly repeat infections.
Lowering blood sugar in type 2 diabetes.
for:
Benign prostatic hyperplasia (BPH).
Reducing urinary odor in people with
bladder control problems.
Skin healing.
Pleurisy.
Cancer.
Chronic fatigue syndrome.
Safety
Cranberry juice and extracts are likely safe for
most adults and children.
Side effects
Drinking too much cranberry juice may cause
mild stomach upset and diarrhea.
Cranberries and cranberry juice are safe to
consume during pregnancy and breast-feeding.
It is not known, however, whether dietary
supplements containing cranberry are safe to use
during pregnancy and breast-feeding.
Because cranberries contain signifcant amounts
of salicylic acid, caution should be used before
consumption in patients allergic to aspirin
(acetylsalicylic acid).
Diabetics should avoid the sugar-sweetened
cranberry products.
Elite Page 31
Cranberry juice and extracts contain a large
amount of oxalate. Because kidney stones are
composed of oxalate combined with calcium,
consumption of cranberry juice or extracts may
increase the risk of kidney stones.
Cranberry should be consumed only under
the supervision of a health care provider if the
patient is on anti-coagulants. The dosage of the
anticoagulant may need to be monitored and
adjusted.
Interactions
Cranberry may impede the elimination of
warfarin from the body and thus may increase the
likelihood of bruising and bleeding. The dose of
warfarin may need to be adjusted.
Cranberry may inhibit certain enzymes in the
liver necessary for the metabolism of certain
drugs, possibly increasing their therapeutic
effects and side effects. Patients should consult
with their health care provider before taking
cranberry while on any of the following
medications: amitriptyline, diazepam, zyleutin,
celecoxib, diclofenac, fuvastatin, glipizide,
ibuprofen, irbesartran, losartan, phenytoin,
piroxicam, tamoxifen, tolbutamide, torsemide,
warfarin, and others.
Cranberry has no known interactions with foods
or other herbs and supplements.
Oral dosage
Studies have used the following doses:
To prevent urinary tract infections:
Adults: 1-10 oz. per day of cranberry
juice.
Children: 5 ml/kg daily as 30 percent
cranberry concentrate.
As a urinary deodorizer: 3-6 oz. per day of
cranberry juice.
Echinacea [12, 21, 33, 37, 38, 59, 60, 67-69, 78,
83, 88, 92, 97,102, 103, 142, 168-175]
Background
Echinacea, also known as conefower or black-
eyed susan, is prevalent in North America and
thrives in temperate climates. The aboveground
parts of the plant and roots of echinacea are used
fresh or dried to make teas, juice, extracts, or
topical preparations.
Historical and current use
Echinacea was used by Native Americans for
toothaches, gingivitis, stomach pain, colds,
infections, as a topical disinfectant and for wound
healing. The German Commission E approved
echinacea extracts for use orally in relieving cold
symptoms, upper respiratory infections, urinary
tract infections, and topically for superfcial
wounds. Research discloses that echinacea may
help treat, but not prevent, cold symptoms.
Pharmacology
Echinaceas complex chemical makeup is not
fully understood. It contains phenols, such
as caffeic acid, that act to scavenge tissue-
damaging free radicals. Also present are
alkylamides that inhibit cyclooxygenase and
5-lypoxygenase, that explain its anti-infammatory
properties. Echinacea is also thought to have
immunostimulatory properties as demonstrated
by its action in macrophage proliferation,
interleukin-1 and interferon stimulation, and to
increase the numbers of T lymphocytes.
Uses and effcacy
Research results are conficting and inconclusive
about whether echinacea has therapeutic value
in the prevention and treatment of the common
cold. It is noteworthy, though, that a meta-
analysis of three randomized, double-blind and
placebo-controlled trials involving almost 400
subjects found that the risk of developing a cold
was 55 percent higher in the placebo than in the
echinacea-treated group, a statistically signifcant
difference.
There is limited and inconclusive data as
to whether echinacea has other therapeutic
applications, e.g., as an immunostimulant, anti-
infective, or in wound healing.
As with other herbals, the absence of
standardized methods of preparation, the
inadequacy of species identifcation, product
contamination, and dose-to-dose variability
between marketed products on the amount and
type bioactive components add to the conficting
therapeutic effcacy results found in the scientifc
literature.
Adverse effects
The most common adverse reactions seen with
the use of echinacea are allergic rash, nausea,
vomiting, abdominal pain, mild drowsiness, and
headache.
Safety and cautions
Echinacea is generally well-tolerated. Both in
vitro and in vivo studies suggest that even when
administered in doses several-fold higher than
customarily used, echinacea is devoid of toxicity.
Although women who took echinacea during the
frst trimester of pregnancy showed no difference
in fetal health than those who did not, the
absence of defnitive data in this group dictates
that echinacea should be avoided during the frst
trimester of pregnancy.
Interactions
Echinacea might decrease how quickly the
body breaks down caffeine. This may cause an
accumulation of caffeine in the bloodstream
increasing the potential side effects, e.g.,
jitteriness, headache, and rapid heartbeat.
Echinacea might change how the body breaks
down some medications categorized as
Cytochrome P450 substrates. Taking echinacea
along with such a medication might increase
its effects and side effects. Some of these
cytochrome substrate medications include
the statins customarily used to lower high
cholesterol, clarithromycin, cyclosporine,
diltiazem, estrogens, indinavir, triazolam,
clozapine, cyclobenzaprine, fuvoxamine,
haloperidol, imipramine, mexiletine, olanzapine,
pentazocine, propranolol, tacrine, theophylline,
zileuton, and zolmitriptan.
Medications that depress immune response are
known as immunosuppressants. Echinacea
can increase the immune response. Thus,
taking echinacea with some medications that
decrease immune response might undermine
the effectiveness of the immunosuppressants
and may lead to serious medical complications,
possibly including organ rejection in transplant
patients. Some of these immunosuppressants
include azathioprine, basiliximab, cyclosporine,
daclizumab, muromonab-CD3, mycophenolate,
tacrolimus, sirolimus, prednisone, and
corticosteroids.
Echinacea increases the absorption of midazolam
and thus might increase its effects and side effects
as well.
Dosage
There is no established dosage for Echinacea.
Studies conducted to determine whether
echinacea is effective to treat cold symptoms and
upper respiratory infections have used a dosage
range of 300-1,000 mg for fve to seven days.
Evening primrose oil [15, 43, 125, 142, 161]
Background
Evening primrose oil is obtained from the seed
of the evening primrose plant and contains fatty
acids. Essential fatty acids are required by the
body for growth and development, and must
be obtained from the diet. In foods, evening
primrose oil is used as a dietary source of
essential fatty acids. In manufacturing, evening
primrose oil is used in soaps and cosmetics.
Uses
Evening primrose oil has been used for skin
disorders, such as eczema, psoriasis and acne;
rheumatoid arthritis; osteoporosis; multiple
sclerosis; cancer; high cholesterol; heart disease;
dyspraxia; intermittent claudication; alcoholism;
Alzheimers disease; schizophrenia; chronic
fatigue syndrome; asthma; diabetic peripheral
neuropathy; neurodermatitis; hyperactivity;
and attention defcit-hyperactivity disorder;
weight loss; whooping cough; irritable bowel
syndrome; peptic ulcer disease; pre-eclampsia;
shortening or starting labor; preventing late
deliveries; premenstrual syndrome; breast pain;
endometriosis; and hot fashes.
Effcacy
The effectiveness ratings for evening primrose
oil are:
Breast pain, but not long-term, severe
breast pain.
Osteoporosis, in combination with
calcium and fsh oils.
Symptoms of premenstrual syndrome.
Attention defcit-hyperactivity disorder.
Reducing symptoms associated with
eczema.
Menopausal hot fashes and night sweats.
for:
Rheumatoid arthritis pain.
Page 32 Elite
Shortening labor, pre-eclampsia, or
preventing late deliveries.
Sjogrens syndrome (an autoimmune
disorder in which the glands that produce
tears and saliva are destroyed).
Cancer.
Acne.
Multiple sclerosis.
Heart disease.
High cholesterol.
Alzheimers disease.
Safety and cautions
Evening primrose oil is likely safe for most
people.
It is only possibly safe during pregnancy and
if breast-feeding, so consumption should be
avoided because there is a lack of reliable studies
in the patient population.
Evening primrose oil may increase the chance
of bruising and bleeding. Use in patients with
a clotting or blood disorder should be avoided
unless under direct supervision of a health care
provider.
Evening primrose oil consumption should be
stopped at least two weeks before any scheduled
surgery.
Evening primrose oil may make seizures more
likely in people with a history of seizures, so
use should be avoided. Seizures have been
reported in people with schizophrenia treated
with phenothiazine drugs, GLA (gamma linolenic
acid-a chemical found in evening primrose oil),
and vitamin E.
Side effects
Side effects are generally mild and include upset
stomach, nausea, diarrhea, and headache.
Interactions
Evening primrose oil contains GLA (gamma-
linolenic acid) that may slow blood clotting, thus
increasing the chances of bruising and bleeding.
Use of evening primrose oil without prescriber
approval is discouraged in patients taking any
of the following medications that also slow
blood clotting: aspirin, clopidogrel, nonsteroidal
anti-infammatory drugs (NSAIDs) such as
diclofenac, ibuprofen, naproxen, dalteparin,
enoxaparin, heparin, warfarin, and others.
Evening primrose oil when taken with
phenothiazines (chlorpromazine, fuphenazine,
trifuoperazine, thioridazine) may increase the
risk of having a seizure.
Using evening primrose oil with other herbs, e.g.,
angelica, clove, danshen, garlic, ginger, ginkgo,
red clover, and turmeric that can slow blood
clotting could increase the risk of bleeding in
some people.
There are no known interactions with foods.
Oral dosage
There is no established dosage for evening
primrose oil. Use for breast pain has been in the
range of 3-4 grams daily.
Garlic [1, 2, 3, 6, 17, 36, 44-46, 51, 57-59, 70,
79, 80, 83, 84, 89, 95, 110, 117, 125]
Background and historical uses
Garlic, also known as allium, is related to chives
and onions. Garlic is the edible bulb from the
plant, used as both a medicine and a spice for
thousands of years. Historically, garlic has been
used for high cholesterol, heart disease, high
blood pressure, and cancer prevention, e.g.,
stomach and colon cancers. Garlic cloves can be
eaten raw or cooked. They may also be dried or
powdered and used in tablets and capsules. Raw
garlic cloves can be used to make oils and liquid
extracts.
Pharmacology
More than 20 sulfur compounds have been
identifed in garlic. These compounds include
allinin and the peptides, steroids, terpenoids,
favonoids, and phenols.
Methyl-allyl trisulfde, an allicin derivative,
inhibits cyclooxygenase activity and
prostaglandin synthesis thar may explain the
anti-thrombotic and anti-platelet aggregation
properties of garlic.
Garlic has also been studied for potential use in
the treatment of stomach and colorectal cancer.
This potential use may arise from the presence in
garlic of diallyl trisulfde, a sulfur compound that
is a potent inhibitor of colon and lung cancer cell
proliferation.
Clinical trials
Reliable and consistent evidence of medicinal
benefts of garlic are few.
In one study, garlic lowered total cholesterol
levels by 8 percent to 15 percent (lowering low-
density lipoprotein and triglycerides, but with no
change in high-density lipoproteins). A meta-
analysis, however, found the reduction to be only
4 percent to 6 percent and was not statistically
signifcant after a six-month period.
Garlic has also been shown to inhibit platelet
aggregation, as expected by its inhibitory effects
on cyclooxygenase and prostaglandin synthesis.
The effective dosages have not been established,
and it is unknown how garlic compares to
anti-platelet drug therapy. Because of reports
associating garlic with bleeding incidents,
co-administration of garlic with anti-platelet
aggregation drugs (e.g., aspirin) or anticoagulants
(e.g., warfarin), should be avoided.
Epidemiological studies suggest that regular
consumption of garlic may lower risk of
developing gastric and colorectal cancers, but
more investigation is needed before a defnitive
answer can be formulated.
Effcacy
The effcacy rating for garlic is as follows:
High blood pressure.
Hardening of the arteries
(atherosclerosis).
Preventing colon cancer, rectal cancer,
and stomach cancer.
Preventing tick bites.
Fungal skin infections.
Diabetes.
Treating H. pylori, a bacterium that can
cause ulcers.
High cholesterol.
Breast cancer.
Lung cancer.
Treating peripheral arterial occlusive
disease.
for:
Treating high cholesterol in HIV/AIDS
patients.
Common cold or fu.
Benign prostatic.
Hyperplasia.
Arthritis.
Allergies.
Travelers diarrhea.
Pre-eclampsia.
Male urinary tract problems.
Preventing prostate cancer.
Warts and corns.
Interactions and adverse effects
The interaction between garlic and anticoagulants
and anti-platelet aggregation agents such as
warfarin, heparin, ticlopidine, and clopidogrel
is clinically signifcant in that a potentiation of
the activity of these drugs occurs when co-
administered with garlic.
Garlic also reduces by 50 percent the plasma
concentration of the protease inhibitor/HIV
drug saquinavir. This is a dangerous interaction,
so in an abundance of caution, use of garlic
in patients taking any protease inhibitor is not
recommended.
The most common adverse effects reported are
bad breath and body odor. Other side effects
include dyspepsia, fatulence, dermatitis, and
respiratory diffculty in hypersensitive patients.
Safety
Garlic is safe in most populations at customary
doses. Patients allergic to garlic, chives, onions,
leeks, or lilies should avoid use of garlic.
Dosage
There is no established dosage for garlic;
however, studies have been conducted using
garlic preparations having 1.3 percent allinin
or 0.6 percent allicin that are administered at
600-900 mg per day (approximately equal to one
small clove of fresh garlic).
Ginkgo [4, 9, 20, 22, 23, 33, 45, 47-50, 53, 56,
66, 71, 83, 116, 119, 163]
Background and historical uses
Ginkgo (Ginkgo biloba), also known as kew tree,
is an herb from which the leaves are generally
used to make extracts. Ginkgo extracts have been
used for centuries in traditional Chinese medicine
to treat disorders such as asthma, allergies,
premenstrual syndrome, tinnitus, cognitive
impairments, and central and peripheral vascular
insuffciencies.
Elite Page 33
Pharmacology
More than 40 chemical compounds have been
isolated from ginkgo and include favonoids,
terpenoids, favones, catechins, sterols, and
organic acids. Ginkgo biloba extracts available in
Europe and North America are standardized to 24
percent favonoids and 6 percent terpenoids.
Because of the complex interactions among
chemical components, it is diffcult to establish
a well-defned cause-effect relationship between
specifc elements and biological effects.
Nevertheless, it is now known that favonoids
have antioxidant properties and are free-radical
scavengers.
Flavonoids also provide a protective effect
against apoptosis and beta-amyloid neurotoxicity
of Alzheimers disease and help prevent neuronal
degeneration in Parkinsons disease. Terpenoids
prevent platelet aggregation, have anti-
infammatory properties, and prevent contraction
of smooth muscles in the respiratory tract.
Effcacy
The effectiveness ratings for ginkgo are as
follows:
Improving symptoms of Alzheimers,
vascular, or mixed dementias.
Ginkgo biloba extract stimulates
receptor expression and neurotransmitter
concentrations in the brain, particularly
acetylcholine.
Improving short-term visual memory
and speed of mental processing in
nondemented people with age-related
memory loss.
Improving thinking skills in healthy
young to middle-aged people.
Reducing the number of painful attacks
in people with Raynauds syndrome.
Increasing the distance people with poor
blood circulation in their legs can walk
without pain, and may reduce the need
for surgery.
Reducing symptoms associated with
dizziness and balance disorders.
Relieving PMS-related breast tenderness.
Improving pre-existing visual feld
damage in people with normal tension
glaucoma.
Improving color vision in diabetics.
Treating ringing in the ears.
Treating depression in those suffering
seasonal affective disorder.
Treating sexual problems related to
antidepressant medicines.
Preventing symptoms of altitude
sickness.
Reducing the chance of having a heart
attack, chest pain, or stroke.
for:
Reducing age-related macular
degeneration.
Decreasing symptoms of anxiety in adults
with generalized anxiety disorder or
adjustment disorder with anxious mood.
Reducing anxiety, hyperactivity and
impulsiveness symptoms in patients with
attention defcit-hyperactivity disorder.
Improving clot-related stroke recovery.
Recovering short-term hearing loss from
unknown causes.
Reducing pain of fbromyalgia.
Reducing the negative effects of radiation
exposure on the body.
Decreasing high cholesterol.
Preventing atherosclerosis.
Reducing likelihood of blood clots.
Preventing heart disease.
Preventing or treating colorectal or
ovarian cancers.
Reducing symptoms of chronic fatigue
syndrome.
Treating coughs.
Improving symptoms of asthma and
bronchitis.
Treating digestive disorders.
Preventing and treating urinary problems.
Allergies and side effects
Ginkgo can cause some minor side effects, such
as headache, nausea, dizziness, constipation, and
forceful heartbeat. Ginkgo fruit and pulp can
cause severe allergic skin reactions and irritation
of mucous membranes. There also may be ginkgo
cross-allergenicity in people who are allergic to
poison ivy, poison oak, poison sumac, mango
rind, or cashew shell oil.
Safety
Ginkgo leaf extract is likely safe when taken
orally in appropriate doses in adults and children
for up to six months.
Ginkgo is possibly unsafe when used during
pregnancy and may cause early labor or extra
bleeding during delivery. Although in vivo
studies did not disclose any embryotoxic or
teratogenic effects, ginkgo extract should be
avoided during pregnancy and breastfeeding.
In animals, extremely high doses of ginkgo leaf
increased the risk of liver and thyroid cancers,
but there is insuffcient information on humans.
Ginkgo leaf extract may increase the risk of
bruising and bleeding and decreases the bloods
ability to form clots. Bleeding into the eye and
brain and excessive bleeding following surgery
have been observed in a few patients.
The roasted ginkgo seed or crude ginkgo plant
is possibly unsafe when taken by mouth. Eating
more than 10 roasted seeds a day can cause
diffculty breathing, weak pulse, seizures, loss
of consciousness, and shock. The fresh seed
is poisonous, and may cause seizures, loss of
consciousness, and death.
Ginkgo may:
Affect blood sugar levels.
Cause seizures. Avoid use in seizure patients.
Impede conception.
Worsen bleeding disorders.
Slow blood clotting, resulting in excessive
bleeding during and after surgery. Ginkgo
should be stopped at least two weeks before
any scheduled surgery.
Interactions
Ginkgo interacts with almost 500 drugs and drug
combinations. Because of the sheer quantity of
interactions, it is wise to consult a comprehensive
database, such as http://www.drugs.com/drug-
interactions/ginkgo,ginkgo-biloba-index.html#S,
for a clearer picture. In light of the quantity of
potential interactions, this will address the more
frequently encountered and more serious ones.
Ginkgo may decrease the effects of antiviral
agents, such as efavirenz and indinavir, used to
treat HIV.
Ginkgo may increase or decrease the therapeutic
action of drugs that are metabolized by certain
specifc enzymes in the liver. Some of these drugs
that are changed by the liver include clozapine,
cyclobenzaprine, fuvoxamine, haloperidol,
imipramine, mexiletine, olanzapine, pentazocine,
propranolol, tacrine, theophylline, zileuton,
zolmitriptan, amitriptyline, carisoprodol,
citalopram, diazepam, lansoprazole, omeprazole,
phenytoin, celecoxib, diclofenac, lovastatin,
fuvastatin, glipizide, ibuprofen, irbesartan,
losartan, piroxicam, tamoxifen, tolbutamide,
torsemide, warfarin, codeine, desipramine,
donepezil, fentanyl, fecainide, fuoxetine,
meperidine, methadone, metoprolol, ondansetron,
tramadol, trazodone, clarithromycin,
cyclosporine, diltiazem, estrogens, indinavir, and
triazolam.
Ginkgo might increase or decrease insulin and
blood sugar in type 2 diabetics, so it is wise to
monitor blood sugar closely. Diabetes medication
might need to be changed or the dose adjusted.
Do not take ginkgo with medications that
lower the seizure threshold and thus increase
the chance of having a seizure. These drugs
include propofol, mexiletine, amphotericin,
penicillin, cephalosporins, imipenem, bupropion,
cyproheptadine, cyclosporine, fentanyl,
methylphenidate, and theophylline.
Ginkgo slows clotting, so taking it with
anticoagulants or anti-platelet drugs that also
slow blood clotting may increase the chances of
bruising and bleeding. Some medications that
slow blood clotting include aspirin, clopidogrel,
dalteparin, enoxaparin, heparin, indomethacin,
ticlopidine, and warfarin. Some herbs and
supplements, such as angelica, clove, danshen,
garlic, ginger, and Panax ginseng, can also slow
blood clotting, thereby increasing the risk of
bleeding in some people. Ginseng should not be
taken with these herbals.
Ginkgo can also affect chemicals in the brain in a
way that may possibly decrease the effectiveness
of medications used to prevent seizures. Some
medications used to prevent seizures include
phenobarbital, primidone, valproic acid,
gabapentin, carbamazepine, and phenytoin.
Page 34 Elite
Ginkgo can alter the blood pressure-lowering
effect of hydrochlorothiazide, which can lead to
elevated blood pressure.
Ginkgo and other herbals that can increase the
risk of seizure should not be taken together.
Herbs and supplements that can increase seizure
risk include butanediol, cedar leaf, Chinese club
moss, EDTA, folic acid, gamma butyrolactone
(GBL), gamma hydroxybutyrate (GHB),
glutamine, huperzine A, hydrazine sulfate, hyssop
oil, juniper, L-carnitine, melatonin, rosemary,
sage, and wormwood.
There are no known interactions of ginseng with
foods.
Dosage
The following oral doses of ginkgo leaf extract
have been studied and used for:
Dementia syndromes: 120-240 mg per day
divided in 2-3 doses.
Cognitive function improvement in healthy
young people: 120-600 mg per day.
Raynauds disease: a dosage of 360 mg per
day divided into 3 doses.
Peripheral vascular disease: 120-240 mg per
day divided into 2-3 doses.
Vertigo: 120-160 mg per day divided into 2-3
doses.
Premenstrual syndrome (PMS): 80 mg
twice daily, starting on the 16th day of the
menstrual cycle until the ffth day of the next
cycle.
Normal tension glaucoma: 40 mg 3 times
daily up to four weeks.
For all uses, it is advisable to start at a dose
not more than 120 mg per day to avoid
gastrointestinal (GI) side effects. Increase to
higher doses as needed. Dosing may vary,
depending on the specifc formulation used.
Ginseng (Panax) [7, 21, 33, 52, 55, 61, 72, 93,
98, 106-108, 113, 115, 120, 125]
Background
Ginseng is a perennial herb that has been used
for medicinal purposes in Asian countries for
centuries. It is harvested in autumn and prepared
from the root of plants that are generally 5-6
years old.
American ginseng (Panax quinquefolius) is native
to the rich hardwood forests of Canada and the
eastern half of the United States. Asian ginseng is
obtained from Panax ginseng. Japanese ginseng
is from Panax japonicas. Siberian (Russian)
ginseng is from E. senticosus, a plant that is not
considered a true ginseng.
The different types should not be interchanged
because they have different medicinal effects.
Because of vast harvesting arising from its
immense popularity and multiple uses, wild
American ginseng is becoming rare. As a result,
some states list it as an endangered plant species.
Historical uses
American ginseng has been used for stress, to
boost the immune system, as a general tonic
and stimulant, to help prevent colds and fu and
reduce severity of symptoms when infections
occur, for dysentery, for pseudomonal infections
in cystic fbrosis patients, to improve digestion,
for loss of appetite, vomiting, colitis, gastritis,
anemia, diabetes, insomnia, nerve pain, erectile
dysfunction, fever, hangover symptoms, attention
defcit-hyperactivity disorder (ADHD), blood
and bleeding disorders, cancer, painful joints,
dizziness, headaches, convulsions, fbromyalgia,
atherosclerosis, memory loss, and as an anti-
aging aid.
Oils and extracts made from American ginseng
are used in soaps and cosmetics.
Pharmacology
American ginseng contains a variety of saponins
called ginsenosides that affect insulin levels,
lower blood sugar, lower blood pressure,
and improve cognitive performance. The
concentration of the various ginsenosides varies
among species, plant age, and season of harvest.
Ginseng also contains polysaccharides that may
affect the immune system.
Both in vitro and in vivo rodent studies
have shown that ginseng extracts have a
neuroprotective effect useful in some types of
Parkinsonism.
Well-designed scientifc studies of ginseng are
limited and have generally failed to support
historical use claims, except possibly some
clinical trials on ginsengs hypoglycemic
properties.
It should be noted that different American
ginseng products may differ in effect because of
varying amounts of ginsenosides.
Effcacy
The effectiveness ratings for American ginseng
are as follows:
Lowering post-prandial blood sugar in
type 2 diabetics.
Taking 3 grams of American ginseng by
mouth, up to two hours before a meal,
can signifcantly lower blood sugar after
a meal, but larger doses dont seem to
lower blood sugar more.
Preventing and reducing symptom
severity in adult respiratory tract
infections, e.g., infuenza and common
cold.
for:
Attention defcit-hyperactivity disorder
(ADHD).
Breast cancer.
Athletic performance. Ginseng may
decrease muscle damage during exercise.
Stress.
Anemia.
Insomnia.
Gastritis.
Impotence.
Fever.
HIV/AIDS.
Fibromyalgia.
American ginseng is possibly safe in adults and
children when used short-term.
American ginseng is possibly unsafe in
pregnancy because of the possibility of birth
defects. American ginseng should be avoided in
pregnancy. Because there is insuffcient evidence
about it, American ginseng should be avoided if
breast-feeding.
Adverse reactions and side effects
American ginseng may lower blood sugar and
has been linked to insomnia.
Patients suffering from estrogen-sensitive
conditions, such as breast cancer, uterine cancer,
ovarian cancer, endometriosis, or uterine fbroids,
should not take American ginseng unless the
ginsenosides have been removed or if the
preparation contains only low concentrations of
ginsenosides.
Common side effects seen with use of American
ginseng include diarrhea, itching, insomnia,
headache, nervousness, rapid heartbeat, blood
pressure alterations, breast tenderness, and
vaginal bleeding.
Uncommon side effects that have been reported
include liver damage, Stevens-Johnson syndrome,
severe allergic reaction, and estrogen-like effects
in men, e.g., reduced libido and gynecomastia.
Interactions
Long-term use of American ginseng has been
reported to induce the hepatic enzyme CYP450
that increases the metabolism of warfarin by
the body. This enzymatic effect decreases the
effect of warfarin, thereby increasing the risk of
clotting. In an abundance of caution, American
ginseng should not be consumed by patients
taking anticoagulant medications. In contrast,
the anticoagulant properties of ginseng may also
account for a few instances of nose and vaginal
bleeding.
Ginseng has been shown to potentiate action
of many anti-hypertensive medications. Thus,
ginseng should be avoided in patients taking
blood pressure medications absent physician
supervision.
Use of American ginseng with monoamine
oxidase inhibitors, e.g., phenelzine and
tranylcypromine, used for depression, may result
in enhanced side effects such as anxiousness,
headache, mood disorders, nervousness,
restlessness, and insomnia.
There are no known interactions with food, herbs
or other supplements.
Safety
Ginseng preparations are generally safe and
well tolerated when administered within the
recommended dosage. Nevertheless, ginseng
should be avoided during pregnancy and
breastfeeding. Although one respiratory tract
infection study in Canada involving 75 pediatric
patients showed ginseng to be safe when
given at standard and low doses. Additional
research is needed before use in children can be
recommended.
Elite Page 35
Dosage
Purifed ginseng extracts are generally
standardized to 4 percent or 7 percent ginsenoside
contents. The usual oral dose of standardized
4 percent extract is 100-200 mg once or twice
daily, for up to 12 weeks. Dried ginseng root
in amounts equivalent to 200-600 mg of
standardized extract has been used for years in
China.
Long-term use of ginseng should not exceed 1 g/
day (dry root) or 400 mg/day (extract). A ginseng
treatment schedule of 2 to 3 weeks on, then 1 to 2
weeks off, may be repeated for several months.
Kava [5, 18, 33, 42, 44, 73, 83, 87, 90, 143, 163]
Background
Kava, a plant native to the South Pacifc, is a
member of the pepper family. It is also known as
kava-kava, kawa, or ava pepper. The root is used
for medicine. Whole kava roots are chewed for
their medicinal value. Kava is available as liquid
tinctures or standardized extracts, and powdered
in capsules or tablets. A tea can also be made by
simmering the plant roots in water.
The main active ingredients in kava root are
kavalactones (kavapyrones). These chemical
compounds have been extensively studied and
found to reduce convulsions, promote sleep,
and relax muscles in animals. They also have
pain-relieving properties, which may explain
why chewing kava root causes some temporary
numbness and tingling sensation on the tongue.
Kava also contains antioxidant favonoids and
alkaloids.
Historical and current uses
Kava is used to relieve anxiety, stress,
restlessness, and treat sleep problems. It has
also been used for attention defcit-hyperactivity
disorder (ADHD), epilepsy, psychosis,
depression, migraines and other headaches,
chronic fatigue syndrome, respiratory tract
infections, tuberculosis, muscle pain, cancer
prevention, urinary tract infections, pain
and swelling of the uterus, venereal disease,
menstrual discomfort, and to arouse sexual
desire.
Kava has been used topically on skin diseases,
including leprosy, to promote wound healing and
as a painkiller. As a mouthwash, it is used for
canker sores and toothaches.
Effcacy
The effectiveness ratings for kava are as follows:
Anxiety.
Review of seven scientifc studies
concluded that a standardized kava
extract was signifcantly more effective
than placebo in treating anxiety. Another
study found symptoms improved after
only one week of treatment. Kava may
be as effective as some prescription
anti-anxiety medications. Another study
involving kava and diazepam showed
similar brain wave activity changes,
suggesting that they may work in the
same ways to calm the mind. There
is also evidence that 300 mg of kava
may improve mood and cognitive
performance. This is signifcant because
benzodiazepines (e.g., diazepam and
alprazolam), used to treat anxiety often
decrease cognitive function. Anxiety-
related research on kava has decreased
because of reports of liver toxicity.
Insomnia.
Preliminary evidence suggests that
kava may help improve sleep quality
and decrease the amount of time
needed to fall asleep. Because of safety
concerns, other herbs and drugs to treat
sleeplessness should be considered before
using kava.
Insuffcient evidence as to effectiveness for:
Cancer prevention.
Restlessness.
(ADHD).
Epilepsy.
Psychosis.
Depression.
Headaches.
Colds and respiratory tract infections.
Tuberculosis.
Chronic bladder infections.
Sexually transmitted diseases.
Menstrual problems.
Safety and warnings
There are some big safety concerns arising from
many cases of liver damage and deaths in patients
with previously healthy livers traced to kava use.
Kava has been banned in Switzerland, Germany,
and Canada, and several other countries are
considering similar action.
Given these injuries even after short-term use
(one to three months), it is impossible to say what
dose of kava may be safe. The FDA has advised
health care professionals of possible health
risks of consuming kava. It is not recommended
for use in the U.S., but if used, should only be
administered under a doctors supervision.
Kava should never be given to children.
Using kava can make you unable to drive or
operate machinery safely.
In addition to liver damage, kava should not be
used during pregnancy or while breast-feeding
because of possible harm to the uterus and
passage of its potentially dangerous chemicals
into breast milk.
Kava may also worsen depression.
Kava affects the central nervous system and
may increase the effects of anesthesia and other
medications used during and after surgery. Stop
using kava at least two weeks before a scheduled
surgery.
Side effects
Side effects associated with kava include allergic
and contact dermatitis, dizziness, drowsiness,
restlessness, stomach upset, tremors, dry,
discolored skin, hair loss, partial loss of hearing,
and loss of appetite. Like alcohol, kava may
have intoxicating effects and should not be taken
before operating a car or other machinery.
Interactions
Kava may increase:
The effects of anti-convulsant medications,
e.g., phenytoin.
The chance of liver function impairment and
damage if combined with alcohol.
The effects of benzodiazepines, e.g.,
alprazolam, diazepam.
Lorazepam, clonazepam, triazolam, and
chlordiazepoxide, used for anxiety.
The effects of barbiturates, e.g.,
pentobarbital, used for sleep disorders.
The effects of diuretics, enhancing the risk of
dehydration.
The risk of side effects associated
with phenothiazine medications, e.g.,
chlorpromazine, used for the treatment of
schizophrenia, and promethazine, used as an
antihistamine and anti-nausea agent.
The risk of liver damage if combined with
drugs that may also harm the liver. Some
medications that can harm the liver include
acetaminophen, amiodarone, carbamazepine,
isoniazid, methotrexate, methyldopa,
fuconazole, erythromycin, phenytoin,
lovastatin, pravastatin, and simvastatin.
The risk of harm to the liver if combined with
other herbs known to detrimentally affect
the liver. Some of these products include
androstenedione, chaparral, comfrey, DHEA,
germander, niacin, pennyroyal oil, and red
yeast.
Kava may reduce the effectiveness of levodopa
used to treat Parkinsons disease.
Kava affects medications that are metabolized
by the liver. Some medications that are changed
by the liver include clozapine, cyclobenzaprine,
fuvoxamine, haloperidol, imipramine,
mexiletine, olanzapine, pentazocine, propranolol,
tacrine, theophylline, zileuton, zolmitriptan,
dsipramine, donepezil, fentanyl, fecainide,
fuoxetine, metoprolol, meperidine, methadone,
tramadol, trazodone, amitriptyline, diazepam,
zileuton, celecoxib, diclofenac, lovastatin,
fuvastatin, glipizide, ibuprofen, irbesartan,
losartan, phenytoin, piroxicam, tamoxifen,
tolbutamide, torsemide, warfarin, acetaminophen,
chlorzoxazone, ethanol, theophylline,
ketoconazole, itraconazole, and fexofenadine.
Kava should be discontinued at least 24 hours
before surgery because of a possible effect of
anesthetics used during surgery, e.g., enfurane,
halothane, isofurane, and methoxyfurane.
Kava can cause enhanced sleepiness or
drowsiness if used in conjunction with other
herbs and supplements that have the same effect.
Some of these herbs and supplements include
5-HTP, calamus, California poppy, Jamaican
dogwood, catnip, hops, St. Johns wort, skullcap,
valerian, and yerba mansa.
Page 36 Elite
Dosage
Currently, there is not enough scientifc
information to determine an appropriate range
of doses for kava. Standardized products are,
however, available, with dosages of kavalactones
ranging from 120-250 mg/day. In the U.S., most
formulations are standardized to 30 percent or
55 percent, i.e., a 100 mg tablet contains 30 mg
or 55 mg of kavalactones, respectively. Although
use is discouraged, any kava use should be
limited to less than 3 months.
Melatonin [125, 152]
Background
Melatonin is a naturally occurring hormone that
regulates night/day cycles or sleep-wake cycles.
Darkness induces the production of melatonin to
prepare the body for sleep, and light decreases
it to prepare for awakening. It is thought that
supplementing natural stores of melatonin might
help those who have diffculty sleeping.
Uses and effcacy
The effectiveness ratings for melatonin are as
follows:
Likely effective for:
Disturbed sleep-wake cycles in children
and adolescents with mental retardation,
autism, and other central nervous system
disorders.
Sleep disorders in blind people.
Improving jet lag-related alertness,
tiredness, movement coordination, and
the time it takes to fall asleep.
Trouble sleeping.
Reducing the number of cluster
headaches.
Reducing anxiety before surgery (taken
sublingually).
Helping elderly people sleep after
discontinuing use of benzodiazepines.
Helping reduce symptoms associated
with smoking cessation.
Improving the effectiveness and reducing
side effects of cancer medications used
for tumors in the breast, lung, kidney,
liver, pancreas, stomach, colon, and
prostate.
Decreasing symptoms of a movement
disorder called tardive dyskinesia.
Decreasing sunburn (applied topically as
a cream before sun exposure).
Adjusting shift work-related sleep
disorders.
Depression (may actually worsen
symptoms).
for:
Menopausal symptoms.
Migraine headache.
Evidence suggests that taking
melatonin at bedtime can prevent
episodic migraine headache. When
headaches do occur, they are milder
and pass more quickly. Some
researchers believe that melatonin
production might be altered in
migraine sufferers.
Insomnia caused by high blood pressure
medications, e.g., beta-blockers.
Ringing in the ears (tinnitus).
Osteoporosis.
Irritable bowel syndrome.
Birth control.
Fibromyalgia.
Safety
Melatonin is likely safe for most adults when
taken by mouth short-term or applied to the skin.
Melatonin may interfere with ovulation, making
it more diffcult to conceive. Not enough is
known about the safety of melatonin when
breast-feeding. It is advisable to avoid melatonin
if pregnant, trying to become pregnant, or if
breast-feeding.
Because it may affect other hormones and
thus may interfere with development during
adolescence, use in most children should be
avoided.
Melatonin can raise blood pressure, increase
blood sugar, worsen symptoms of depression,
and increase the risk of seizures. In hypertensive
patients, diabetics and those who have previously
experienced a seizure, caution and close
monitoring is recommended.
Side effects
Side effects observed with melatonin use include
daytime sleepiness, dizziness, headaches,
abdominal discomfort, mild anxiety, irritability,
confusion and brief feelings of depression.
Interactions
Because melatonin may cause sleepiness and
drowsiness, combining it with other sedative
medications such as clonazepam, lorazepam,
diazepam, phenobarbital, and zolpidem may
cause too much drowsiness.
Birth control pills increase the amount of
melatonin the body makes, resulting in
abnormally high levels of melatonin.
Caffeine may decrease the effectiveness of
melatonin.
Fluvoxamine can increase the amount of
melatonin that the body absorbs and thus may
increase the effects and side effects of melatonin.
Melatonin can increase blood sugar and
thus may decrease the effectiveness of
diabetes medications such as glimepiride,
glyburide, insulin, pioglitazone, rosiglitazone,
chlorpropamide, glipizide, and tolbutamide.
Melatonin might decrease the effectiveness
of immunosuppressants medications such
as azathioprine, basiliximab, cyclosporine,
daclizumab, muromonab-CD, mycophenolate,
tacrolimus, sirolimus, prednisone, and
corticosteroids.
Taking melatonin with medications that slow
clotting might increase the chances of bruising
and bleeding. Medications known to slow blood
clotting and impair platelet aggregation include
aspirin, clopidogrel, diclofenac, ibuprofen,
naproxen, dalteparin, enoxaparin, heparin, and
warfarin.
Melatonin may decrease the anti-hypertensive
activity of nifedipine.
Verapamil can increase the speed at which the
body metabolizes melatonin, so may decrease the
effectiveness of melatonin.
Flumazenil may decrease the effects of
melatonin.
Melatonin may increase the effect of herbs that
slow blood clotting and thus might increase the
risk of bleeding. Some herbs that slow blood
clotting include angelica, clove, danshen, garlic,
ginger, ginkgo, Panax ginseng, red clover, and
willow.
Using melatonin along with herbs having sedative
properties, e.g., 5-HTP, calamus, California
poppy, catnip, hops, Jamaican dogwood, kava,
St. Johns wort, skullcap, valerian, and yerba
mansa, may increase the effects and side effects
of melatonin.
There are no known interactions of melatonin
with foods.
Dosage
The following oral doses have been used in
scientifc studies for:
Insomnia:
Adults: 0.3-5 mg at bedtime.
Children: 5 mg at 6 or 8 p.m.
Jet lag:
0.5-5 mg at bedtime on the arrival day,
continuing 2-5 days.
Tardive dyskinesia:
10 mg daily of a controlled-release
formulation.
Solid tumors in combination with
conventional therapy: 10-50 mg along with
radiotherapy, chemotherapy, or interleukin.
Melatonin is typically started seven days
before the start of chemotherapy and
continued throughout full treatment course.
Prostate cancer that has spread to other
sites (metastatic cancer) and is resistant to
triptorelin used alone: 20 mg taken daily has
been used in combination with 3.75 mg of
triptorelin injected into the muscle every 28
days.
Prevention and treatment of low platelets
associated with cancer chemotherapy: 20 mg
each evening.
Benzodiazepine withdrawal in elderly people
with insomnia: 2 mg of controlled-release
melatonin taken at bedtime for six weeks.
Benzodiazepine dosage is reduced 50 percent
during the second week, 75 percent in weeks
three and four, and stopped during weeks
fve and six. Therapy may continue up to six
months.
Prevention of cluster headache: an evening
dose of 10 mg.
Elite Page 37
Reducing anxiety before surgery in adults:
0.05 mg/kg under the tongue.
Nicotine withdrawal symptoms: 0.3 mg
orally 3.5 hours after stopping smoking.
Saw palmetto [8, 10, 11, 13, 16, 19, 24, 33, 39,
40, 74, 77, 83, 91, 104, 105, 111, 116- 118, 125,
154]
Background
Saw palmetto is a fan palm, dwarf palm or
cabbage palm that grows as a tree or shrub in the
warm climates of the coastal southeast U.S., from
South Carolina to Florida. The plant has white
fowers that produce yellow berries.
Saw palmettos active ingredients include fatty
acids, plant sterols, and favonoids. The berries
contain high molecular weight polysaccharides
(sugars) that may reduce infammation and
strengthen the immune system.
Saw palmetto is commercially available as
dried berries, powdered capsules, tablets, liquid
tinctures, liposterolic extracts, and a tea. The
product label should indicate that contents are
standardized and contain 85-95 percent fatty
acids and sterols.
Historical and current uses
Historically, saw palmetto has been used to
treat urinary tract problems, to increase sperm
production, for colds and coughs, sore throat,
asthma, bronchitis, chronic pelvic pain syndrome,
hormone imbalance, migraine headache, prostate
hyperplasia and cancer, as a diuretic, as a
sedative, as an antiseptic, and to enhance sexual
drive.
Today, the primary use of saw palmetto is to
treat benign prostatic hyperplasia (BPH), a
noncancerous enlargement of the prostate gland.
The urethra, the tube that empties urine from
the body, runs through the prostate gland. When
the prostate gland is enlarged, men may have
diffculty urinating.
Pharmacology
It is thought that saw palmetto may inhibit an
enzyme that affects the level of testosterone, may
reduce the amount of an enzyme that promotes
the growth of prostate cells, and may shrink the
inner lining that puts pressure on the tubes that
carry urine. Saw palmetto has a mechanism of
action similar to fnasteride and dutasteride, two
common drugs used to treat BPH. Interestingly,
saw palmetto also inhibits cell proliferation and
promotes programmed death of prostate cancer
cells. Its anti-infammatory properties have been
linked to its inhibitory actions on cyclooxygenase
and lipoxygenase. These combined mechanisms
may synergistically contribute to the therapeutic
effcacy of saw palmetto extracts.
Because of the short duration of the clinical
studies (less than three months), it is not possible
to say whether saw palmetto is truly effective
in treating or preventing symptoms of BPH.
Some studies show symptomatic improvement
in symptoms, such as frequent urination, trouble
starting or maintaining urination, and nocturnal
urination. Other studies show that saw palmetto
is as effective in treating symptoms as fnasteride,
but without the loss of libido side effects. Animal
studies indicate that saw palmetto inhibits the
growth of tumor cells, thus may possibly be
helpful in treating prostate cancer.
Effcacy
In 2002, Wilt et.al. analyzed the results from 21
clinical trials involving more than 3,000 patients.
These trials assessed the effcacy of saw palmetto
versus placebo and fnasteride with respect to
urinary symptoms (dysuria, fullness, bladder
residual volume), nocturia, urine fow rate, and
prostate size). The authors concluded that men
taking saw palmetto were nearly twice as likely
to report improvement in symptoms than those
taking placebo.
Additionally, the saw palmetto patients had
responses similar to those found for fnasteride
with urologic symptoms and fow measures, but
with a lower rate of impotence.
Another study involving more than 2,500 patients
suffering from mild-to-moderate BPH compared
the effectiveness of saw palmetto to tamsulosin
(704 patients) and fnasteride (1,098 patients),
using two different doses of saw palmetto (160
mg twice a day or 320 mg once a day).
The study disclosed a better outcome for patients
taking saw palmetto than those taking either of
the conventional drugs. Unlike the conventional
drugs, sexual dysfunction was not reported
in patients treated with saw palmetto. Co-
administration of saw palmetto and fnasteride
did not improve the treatment outcome.
The absence of effcacy of saw palmetto in some
studies may be attributable to the study being
conducted in moderate-to-severe BPH as opposed
to mild-to-moderate BPH, the failure of the study
to set appropriate dose-response parameters, or
failure to increase the dose of saw palmetto to
adjust for the severity of the medical condition.
Although much of the extensive research on saw
palmetto is conficting on whether saw palmetto
is benefcial in treating prostate symptoms,
there is enough evidence to suggest that saw
palmetto is possibly effective in the treatment of
mild-to-moderate BPH. It is also less expensive,
better tolerated than conventional medications,
and unlike fnasteride and dutasteride, does not
interfere with the laboratory measurements of
prostate specifc antigen (PSA), used to assess the
progression of prostate cancer.
Insuffcient data to support use of saw
palmetto for:
Treating prostate infections.
Chronic pelvic pain syndrome.
Prostate cancer.
Baldness.
Colds and coughs.
Sore throat.
Asthma.
Chronic bronchitis.
Migraine headache.
Increasing breast size.
Reducing bleeding after prostate surgery.
Side effects
Side effects are usually mild and include
dizziness, headache, nausea, vomiting,
constipation, diarrhea, and impotence.
Safety and toxicity
Saw palmetto is likely safe for most people.
No serious toxicities have been reported in the
scientifc literature.
Because of its anti-androgenic properties, women
should not take saw palmetto for treatment of
urogenital problems if they take contraceptives,
hormone replacement therapy, have breast cancer,
or are pregnant. Saw palmetto is likely unsafe
when used during pregnancy or breast-feeding.
Saw palmetto is not recommended for children.
Because saw palmetto might slow blood clotting
and enhance bleeding, saw palmetto should be
stopped at least two weeks before any scheduled
surgery.
A 2008 meta-analysis found serious adverse
effects (e.g., cancer, sexual dysfunction,
hepatoxicity, and respiratory problems) were
no more common in saw palmetto treatment
groups than with placebo. In clinical trials, 3
percent of the saw palmetto subjects developed
hypertension, compared to 2 percent treated
with fnasteride, but this difference was not
statistically signifcant.
Interactions
Because saw palmetto may work similarly to
fnasteride, it is not recommended that saw
palmetto be combined with fnasteride or other
medications used to treat BPH unless directed to
by a physician.
Saw palmetto might slow blood clotting. Taking
saw palmetto with medications that also slow
clotting may increase the chances of bruising
and bleeding. Drugs that slow blood clotting
or impair platelet aggregation include aspirin,
clopidogrel, diclofenac, ibuprofen, naproxen,
dalteparin, enoxaparin, heparin, and warfarin.
Saw palmetto may reduce the number of estrogen
and androgen receptors, possibly reducing the
effectiveness of oral contraceptives and thus
raising the risk of unplanned pregnancy. Taking
saw palmetto along with estrogen replacement
therapy, e.g., conjugated equine estrogens
(Premarin), ethinyl estradiol, and estradiol, may
decrease the effectiveness of these estrogen
replacements.
Saw palmetto may interfere with the absorption
of iron.
There are no known interactions with food, herbs
or supplements.
Dosage
For benign prostatic hyperplasia (BPH): 160 mg
twice daily or 320 mg once daily. Therapeutic
benefts are observed within three to four weeks
after the initiation of treatment, which usually
lasts for three to six months. The general dosage
range is 100-400 mg twice daily.
Page 38 Elite
St. Johns wort [25, 33, 46, 57, 58, 62, 63, 83,
90, 96, 109, 114, 146-150, 155-159, 163]
Background
St. Johns wort is a shrubby plant with clusters
of yellow fowers having oval, elongated petals.
It is native to Europe, parts of Asia and Africa,
Canada, and the western United States. It is
commonly found in the dry ground of roadsides,
meadows, and woods.
The plant gets its name because it is often in
full bloom around June 24, the day traditionally
celebrated as the birthday of John the Baptist.
Wort is an old English word for plant.
Both the fowers and leaves are used as medicine.
St. Johns wort is formulated in capsules, tablets,
as tinctures, as a tea, oil-based skin lotions,
and in chopped or powdered forms of the dried
herb. Most products are standardized to contain
0.3 percent hypericin. The active ingredients in
St. Johns wort are deactivated by light, so it is
packaged in amber containers.
Historical uses
St. Johns wort is an ancient herbal remedy
popularly known as natures Prozac. St. Johns
wort was used as a medicine in ancient Greece
for a range of illnesses, including various nervous
disorders and for its antibacterial, antiviral, and
anti-infammatory properties, e.g., aiding with
wound healing, bug bites, hemorrhoids, and
burns.
Over the years, St. Johns wort has been used to
treat heart palpitations, moodiness, menopause
symptoms, attention defcit-hyperactivity disorder
(ADHD), obsessive-compulsive disorder,
seasonal affective disorder, chronic fatigue
syndrome, smoking cessation, fbromyalgia,
migraine and other types of headaches, muscle
pain, nerve pain, irritable bowel syndrome,
cancer, HIV/AIDS, and hepatitis C.
Pharmacology
The most studied active components of both
the leaves and fowers of St. Johns wort are
hypericin, pseudohypericin, favonoids, and
essential oils. Investigators long believed that
hypericin was responsible for St. Johns worts
action in depression, however, recent studies
suggest that hyperforin may play a larger role in
depression.
Hypericin and hyperforin both act on chemical
messengers in the nervous system that regulate
mood. Clinical studies closely correlate
hyperforin concentrations of 2 percent to 4
percent to antidepressant activity. Both hypericin
and hyperforin inhibit reuptake of serotonin at
the nerve synapse like fuoxetine and paroxetine,
and also inhibit reuptake of dopamine and
noradrenaline, like venlafaxine.
Extracts of St. Johns wort have antibacterial
properties arising from hyperforins inhibitory
effect on the growth of Gram-positive bacteria,
including penicillin-resistant and methicillin-
resistant staphylococcus aureus. This activity
may explain the antiseptic and wound-healing
properties of topical St. Johns wort preparations.
Hyperforin, however, has no effect on Gram-
negative bacteria.
Current uses and effcacy
St. Johns wort is one of the most commonly
purchased herbal products in the United States.
It has been studied extensively as a treatment for
depression. It has fewer side effects than most
other prescription antidepressants. Unfortunately,
it interacts with numerous medications so should
be taken only under medical supervision.
Many studies fnd that St. Johns wort works as
well for mild to moderate depression as selective
serotonin reuptake inhibitors (SSRIs), e.g.,
fuoxetine, citalopram, and sertraline, but without
the loss of sex drive. Researchers are unsure
how St. Johns wort works, but have suggested
that it acts similar to an SSRI, by making more
of the brain chemicals serotonin, dopamine, and
norepinephrine available. These neurotransmitters
help improve ones mood.
The American College of Physicians-American
Society of Internal Medicine suggests that
St. Johns wort is a viable option along with
antidepressant medications for short-term
treatment of mild depression. In contrast, the
National Collaborating Centre for Mental
Health recommends against its use in depression
because of uncertainty about appropriate doses,
persistence of effect, variability in content in the
marketed preparations, and potential serious drug
interactions.
The effectiveness ratings for St. Johns wort are:
Premenstrual syndrome:
Preliminary studies suggest that St.
Johns wort may help relieve the
cramps, irritability, food cravings,
and breast tenderness associated with
PMS by as much as 50 percent in
some women.
Menopause:
Combined with black cohosh, St.
Johns wort may improve mood and
anxiety during menopause.
Seasonal affective disorder:
St. Johns wort has improved mood
and lessened anxiety and sleep
disturbances in people with seasonal
affective disorder, a disorder that
arises from lack of sunlight. An
even greater degree of improvement
is obtained when light therapy is
combined with St. Johns wort.
Eczema, wounds, minor burns,
hemorrhoids:
St. Johns wort has antibacterial
and anti-infammatory properties
helpful in treating minor skin lesions.
Applying St. Johns wort ointment
three times daily for 16 days may
improve wound healing and reduce
scar formation after a cesarean
section.
Obsessive compulsive disorder:
One study found that 450 mg St.
Johns wort twice daily for 12 weeks
improved OCD symptoms. But two
other studies disagreed. Evidence is
conficting. The inconsistent fndings
could be the result of study design
defects and differences in the St.
Johns wort products used.
(ADHD).
Hepatitis C virus (HCV) infection.
HIV/AIDS.
Irritable bowel syndrome.
Diabetic polyneuropathic pain.
Smoking cessation.
Insuffcient evidence for:
Stomach upset.
Bruises.
Skin conditions.
Migraine headaches.
Muscle and nerve pain.
Sciatica.
Excitability.
Fibromyalgia.
Cancer.
Weight loss.
France has banned the use of St. Johns wort
based on a report issued by the French Health
Product Safety Agency warning of signifcant
drug interactions seen with St. Johns wort.
Japan, the United Kingdom, and Canada are in
the process of including drug-herb interaction
warnings on St. Johns wort products. St. Johns
wort is available in the U.S. unrestricted and
over-the-counter.
St. Johns wort can also make the skin overly
sensitive to sunlight. Hats, long sleeved
shirts, and SPF 15 or greater sun screen are
recommended in light-skinned people. Sunlamps,
tanning booths, and tanning beds should be
avoided. St. Johns wort should also be avoided
when taking drugs that produce photosensitivity.
These drugs include amitriptyline,
fuoroquinolone antibiotics, sulfonamides,
tetracycline, and psoralen containing products.
St. Johns wort may interfere with conception
or worsen infertility. Women who are pregnant,
trying to become pregnant, or breastfeeding
should not take St. Johns wort.
It may worsen ADD and ADHD symptoms,
especially when combined with methylphenidate.
St. Johns wort increases the risk of psychosis
and mania in those suffering from schizophrenia,
bipolar disorder, and major depression.
St. Johns wort may elevate thyroid stimulating
hormone (TSH) levels.
St. Johns wort may also contribute to dementia
in Alzheimers patients.
Use of anesthetics in people who have taken St.
Johns wort for at least six months may lead to
Elite Page 39
serious heart complications during surgery. Use
of St. Johns wort should be discontinued at least
two weeks before any scheduled surgery.
Side effects
St. Johns wort is generally well tolerated in
recommended doses for up to 3 months. The most
common side effects include stomach upset, hives
or other skin rashes, fatigue, restlessness, sleep
disturbances, vivid dreams, anxiety, headache,
dry mouth, sexual dysfunction, irritability,
light sensitivity, diarrhea, tingling, dizziness,
and mental confusion. Side effects occur in
1-3 percent of patients, an incidence similar to
placebo and less than standard antidepressant
drugs.
Interactions
St. Johns wort interacts with the following
medications:
Medications used to treat depression or other
mood disorders.
St. Johns wort tends to increase the
side effects associated with these drugs.
The combination may also precipitate
a dangerous and even lethal condition
called serotonin syndrome, which
is characterized by one or more of
the following symptoms: headache,
shivering, palpitations, agitation, rapid
heartbeat, heavy sweating, confusion,
dilated pupils, diarrhea, muscle
rigidity, elevated blood pressure, loss
of muscular coordination, high fever,
unconsciousness, and seizures.
Do not take St. Johns wort with the
following antidepressants:
SSRIs, e.g., citalopram, escitalopram,
fuvoxamine, paroxetine, fuoxetine,
or sertraline.
Tricyclics, e.g., amitriptyline,
nortryptyline, or imipramine.
MAO Inhibitors, e.g., phenelzine,
tranylcypromine, or nefazodone.
Antihistamines such as loratadine, cetirizine,
or fexofenadine. St. Johns wort may reduce
levels of these drugs in the body, making
them less effective.
Clopidogrel. Combining St. Johns wort with
clopidogrel may increase the risk of bleeding.
Dextromethorphan (cough medicine). Taking
St. Johns wort with dextromethorphan, a
cough suppressant, can increase the risk of
side effects, including serotonin syndrome.
Digoxin. St. Johns wort may lower digoxin
levels thereby inhibiting its effectiveness.
Immunosuppressants.
St. Johns wort can reduce the
effectiveness of medications taken
after organ transplant or to control
autoimmune diseases. Taking St.
Johns wort with any of the following
immunosuppressants may even lead
to rejection of the transplanted organ:
adalimumab, azathioprine, cyclosporine,
etanercept, methotrexate, mycophenolate,
or tacrolimus.
Antiretrovirals.
St. Johns wort appears to interact with
protease inhibitors and non-nucleoside
reverse transcriptase inhibitors, such
as indinavir, amprenavir, nelfnavir,
ritonavir, and saquinavir used to treat
HIV and AIDS. The Food and Drug
Administration recommends that St.
Johns wort not be used with any type of
antiretroviral medication.
Birth control pills.
Breakthrough bleeding has occurred
while taking birth control pills and St.
Johns wort. It may be that the herb
can lessen the effectiveness of birth
control pills, so may lead to unplanned
pregnancies.
Aminolevulinic acid.
This drug makes skin more sensitive to
sunlight. St. Johns wort also increases
skin sensitivity to light. The combination
may exert a dangerous impact on skin
sensitivity to the sun.
Reserpine. St. Johns wort may interfere with
reserpines ability to reduce blood pressure.
Sedatives.
St. Johns wort can increase the effect
of drugs having a sedative effect, such
as tricyclic antidepressants, alcohol,
anticonvulsants e.g., phenytoin
and valproic acid, barbiturates
benzodiazepines, and drugs to treat
insomnia, e.g., zolpidem, zaleplon,
eszopiclone, and ramelteon.
Alprazolam. St. Johns wort may speed up
the metabolism of alprazolam in the body,
thereby reducing its effectiveness.
Theophylline. St. Johns wort can lower
blood levels of theophylline, thereby reducing
its ability to open airways in people with
asthma, emphysema, or chronic bronchitis.
Triptans (used to treat migraines)
St. Johns wort increases the side effects
of triptans used to treat and prevent
migraine headaches, even leading to
serotonin syndrome. The tripan group of
drugs includes naratriptan, rizatriptan,
sumatriptan, and zolmitriptan.
Warfarin. St. Johns wort reduces the blood
thinning effectiveness of warfarin.
Drugs metabolized by certain liver enzymes.
St. Johns wort induces the expression of
certain liver enzymes that play a central
role in the metabolism of many drugs.
Hyperforin, an abundant, lipophilic
component of St. Johns wort, contributes
to the therapeutic effects, side effects, and
drug interactions of this herb. St. Johns
wort might affect the speed in which the
liver breaks down some medications.
Taking St. Johns wort along with some
medications that are changed by the liver
can decrease or increase the effectiveness
and side effects of these drugs.
Caution and physician oversight is
recommended before consuming St.
Johns wort if the patient is taking
any of the following medications:
clozapine, cyclobenzaprine, fuvoxamine,
haloperidol, imipramine, mexiletine,
olanzapine, pentazocine, propranolol,
tacrine, zileuton, zolmitriptan,
amitriptyline, nortriptyline, diazepam,
zileuton, celecoxib, diclofenac, anti-
cholesterol statins, glipizide, ibuprofen,
irbesartan, losartan, piroxicam,
tamoxifen, tolbutamide, torsemide,
warfarin, carisoprodol, citalopram,
diazepam, lansoprazole, omeprazole,
phenytoin, ketoconazole, itraconazole,
fexofenadine, triazolam, and many
others.
Drugs moved by pumps in cells
(P-glycoprotein substrates).
St. Johns wort can enhance or diminish
the activity of these cell pumps, thereby
affecting the absorption and effectiveness
of drugs moved in this manner.
Medications that are moved by these
pumps include corticosteroids; vinca
alkaloids, e.g., vinblastine and vincristine,
vindesine; antifungals, e.g., ketoconazole
and itraconazole; antiretrovirals, e.g.,
amprenavir, indinavir, nelfnavir, and
saquinavir; H2 blockers, e.g., cimetidine
and ranitidine; verapamil; diltiazem;
erythromycin; cisapride; fexofenadine;
cyclosporine; loperamide; etoposide;
paclitaxel; and quinidine.
There are no known interactions of St. Johns
wort with food.
Dosage
Clinical trials have used a range of doses of St.
Johns wort that include:
Adults : 500-1,800 milligrams of St. Johns
wort extract daily by mouth.
Most common dosage: 450 mg orally
twice daily or 300 mg 3 times daily.
1.5 percent hyperforin has been applied
to the skin to treat atopic dermatitis.
Children: 150-1,800 milligrams of St. Johns
wort extract by mouth daily.
It may take three to four weeks to feel any effects
from St. Johns wort. Abrupt cessation of St.
Johns wort may cause unpleasant side effects, so
gradually lower the dose before stopping.
Valerian [2 8, 31, 76, 81-83, 86, 99, 100, 121,
122, 125, 144, 145, 153]
Background
Valerian is a perennial plant native to Europe. It
has straight, hollow stems topped by umbrella-
like heads, dark green leaves that are hairy on
the underside, and small, sweet-smelling white,
purple or pink fowers. The light grayish brown
root is pressed into fresh juice or freeze-dried to
form powder and used medicinally. Valerian fuid
extracts and tinctures are available in alcohol
or alcohol-free bases. Powdered valerian is
formulated as a capsule, tablet, and as a tea.
Historical use
Valerian has been used to ease insomnia, anxiety,
nervous restlessness, fatulence, urinary tract
disorders, angina pectoris, congestive heart
Page 40 Elite
failure, and stomach cramps for almost 2000
years. Topically, it has been used to treat acne and
to aid wound healing.
Pharmacology
Various chemical compounds have been extracted
from valerian, e.g., terpenes, valepotriates, amino
acids, and alkaloids. No single compound seems
to account for its pharmacological properties,
however, the biologically active, valerenic or
valeric acid, at concentration of 0.3 percent to
0.8 percent, has been selected for standardization
purposes.
Scientists believe that valerian increases the
amount of gamma aminobutyric acid (GABA) in
the brain. GABA helps regulate nerve cells and
has a calming effect on anxiety. Benzodiazepine
drugs, such as alprazolam and diazepam, also
work by increasing the amount of GABA in
the brain. Valerian may act similarly, but has a
weaker effect.
Current uses
Valerian is most commonly used for sleep
disorders, especially insomnia, but the evidence
is conficting. Valerian is frequently combined
with hops, lemon balm, or other herbs that
also cause drowsiness. Some studies show that
valerian reduces the time it takes to fall asleep
and improves the quality of sleep itself. These
studies confict on the time it takes to adduce
any effect, ranging from almost immediately
to 28 days. Unlike many prescription sleeping
medications, valerian may have fewer side
effects, such as less morning drowsiness.
Some people trying to withdraw from the use of
sleeping pills use valerian to help them sleep
after they have tapered the dose of the sleeping
pill.
Valerian is also used for conditions connected
to anxiety and psychological stress, including
nervous asthma, hysterical states, excitability,
fear of illness, headaches, migraine, and stomach
upset.
Some people use valerian for depression, mild
tremors, epilepsy, attention defcit-hyperactivity
disorder (ADHD), and chronic fatigue syndrome
(CFS).
Valerian is used for muscle and joint pain,
menstrual cramps and symptoms associated with
menopause, including hot fashes and anxiety.
Valerian can be added to bath water to help with
restlessness and sleep disorders.
Valerian extracts and oil are used to favor foods
and beverages.
Effcacy
The effectiveness ratings for valerian are as
follows:
Insomnia
Valerian does not relieve insomnia
as fast as sleeping pills, in some
instances taking up to four weeks for
a noticeable effect. Valerian seems
to improve the sleep quality during
withdrawal from the use of sleeping
pills. Randomized clinical trials
found the effectiveness of valerian
in the treatment of insomnia to be
inconclusive, but the studies may
have been too short in duration to
adequately assess effectiveness.
for:
Anxiety. Again, there is contradictory
evidence as some studies reported a
reduction in stress associated with social
situations, while other studies found no
effect.
Restlessness. A valerian root extract
160 mg combined with lemon balm
leaf extract 80 mg appears to reduce
symptoms of serious restlessness
in children under the age of 12, but
additional research is needed.
Depression.
Convulsions.
Mild tremors.
Epilepsy.
Attention-defcit hyperactivity disorder
(ADHD).
Muscle and joint pain.
Headache.
Stomach upset.
Menstrual pains.
Menopausal symptoms including hot
fashes and anxiety.
Safety
The United States Food and Drug Administration
lists valerian as Generally Recognized As Safe
(GRAS). Germanys Commission E approved
valerian as an effective mild sedative.
Valerian is likely safe for most people when used
in medicinal amounts short-term. Clinical trials
have reported safe use of valerian for medicinal
purposes in more than 12,000 people for up to 28
days. The safety of long-term use is unknown.
Use of valerian in children without doctor
approval is not recommended. There is, however,
some data that suggests valerian might be safe for
use in children for up to eight weeks.
Although test studies show no harmful effects on
fertility or fetal development, it is advisable to
avoid valerian if pregnant or breast-feeding.
Valerian should not be used while driving,
operating heavy machinery, or other activities
that require alertness.
Valerian and anesthesia medications used during
surgery affect the central nervous system. The
combined effects might be harmful. Use of
valerian should be discontinued at least two
weeks before any scheduled surgery.
Side effects
Side effects that have been observed with use
of valerian include allergic reactions, headache,
stomach upset, uneasiness, morning sluggishness,
dizziness, excitability, restlessness, sleeplessness,
dilated pupils, and irregular heartbeat.
Instances of paradoxical reactions, such as
anxiousness and restlessness, have occurred
instead of the desired calm and sleepy effect.
In most cases, valerian does not appear to cause
dependency or signifcant withdrawal symptoms.
However, there have been a few reports of
withdrawal symptoms when valerian was
consumed for very long periods of time. Thus,
it may be advisable to gradually lower doses of
valerian, rather than stopping all at once.
Interactions
Some medications are enzymatically metabolized
in the liver. Valerian might decrease how
quickly these liver enzymes break down some
medications and thus may increase the effects of
these drugs. Some medications changed by the
liver include lovastatin, fuvastatin, ketoconazole,
itraconazole, fexofenadine, triazolam, and others.
Valerian can increase the effects of anti-
convulsant drugs, such as phenytoin and valproic
acid.
Valerian can also increase the drowsiness and
sleepiness symptoms associated with drugs
used in anesthesia and CNS depressants,
such as alcohol, barbiturates, pentobarbital,
phenobarbital, secobarbital, thiopental, fentanyl,
morphine, and propofol. This also may be seen
when valerian is combined with benzodiazepines,
such as alprazolam, diazepam, clonazepam,
lorazepam, midazolam, temazepam, and
triazolam.
Valerian can also increase the effects of drugs
to treat insomnia, such as zolpidem, zaleplon,
eszopiclone and ramelteon, and antidepressants
such as amitriptyline.
Using valerian with alcohol can increase central
nervous system side effects, such as dizziness,
drowsiness, diffculty concentrating, and
impairment in thinking and judgment.
Valerian can also enhance the sedating effects
of other herbs, such as chamomile, lemon
balm, catnip, calamus, California poppy,
hops, Jamaican dogwood, kava, L-tryptophan,
melatonin, sage, St. Johns wort, sassafras, and
skullcap.
Dosage
For insomnia, valerian may be taken one to two
hours before bedtime, or up to three times daily,
with the last dose 30 minutes to 1 hour before
bedtime. It can be consumed as a tea by pouring
1 cup boiling water over 1 teaspoonful (2-3 g) of
dried root, steep fve to 10 minutes; as a tincture
(1:5): 1-1 tsp. (4-6 mL); as a fuid extract (1:1):
to 1 tsp. (1-2 mL); or as a dry powdered extract
(4:1): 250 to 900 mg. A few weeks are generally
needed to see full effects. Once sleep improves,
use should be continued for two to six weeks.
For anxiety: 200 mg 3-4 times daily.
Do not use longer than one month without doctor
approval. To avoid possible side effects after
long-term use, the dose should be gradually
reduced over a week or two before complete
cessation of treatment.
Elite Page 41
Conclusion
In the past 15 years, there has been a dramatic
increase in the popularity and widespread use
of herbal products and dietary supplements. It
is anticipated that the use will continue to rise.
To complicate matters, it is estimated that 70-80
percent of the worlds population takes herbal
supplements, that more than 50 percent of these
patients are also on conventional drug therapy,
yet most do not disclose their herbal consumption
to their health care practitioners.
Reasons for non-disclosure range from concern
over possible negative reaction or lack of interest
by the health care provider; the belief that
because herbals are of natural origin, they are
intrinsically safe and devoid of adverse effects or
toxicity; or the belief that therapeutic ineffcacy is
the worst that could happen from taking herbals.
Most of these reasons have been proven false.
As such, health care providers need to
accommodate for this recent paradigm shift
in therapy. The easiest way to do so is to stay
abreast of current research into this ever-growing
therapeutic area and to establish a habit of
routinely and specifcally asking patients open-
ended, nonjudgmental questions about herbal
medicine use as part of taking a medical history.
Some or all of the following questions may be
helpful:
What herbal supplements, vitamins, or other
over-the-counter remedies are you taking?
How long have you been taking these
products?
At what dose or frequency are you taking
these products?
What purpose or result are you seeking to
achieve from each of these products?
What, if any, side effects or problems have
you experienced?
What, if any, improvement in your health
or condition have you observed that you
attribute to the herbal medicine you take?
Do you have any plant allergies?
Learning about patients use of herbal medicines
(and over-the counter remedies) can strengthen
rapport and build trust. It also allows the
physician an opportunity to consider all factors
affecting the patients health while providing
medical guidance and information on uses,
adverse effects, and interactions. The overall
result enhances the likelihood of successful
therapeutic outcome.
Finally, it is vital to the provision of optimum
health care that health care providers have an
understanding of the pharmacological properties
and therapeutic effcacy of herbal medicines.
Health care providers must be enlightened on
the U.S. regulatory framework applicable to
herbals as compared to drugs; this course has
provided a concise overview of some of the most
common herbal medicines, including their uses,
pharmacology, side effects, interactions, dosages,
and the risks and benefts of their use.
This includes the urgent need to include current
or past use of herbals in patients medical history,
in an effort to provide the safest and most
complete health care possible.
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an independent predictor of mortality in chronic heart failure. J. Am. Coll. Cardiol.
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Natriuretic Peptide [BNP]), and long-term outcome.
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(Final examination on next page)
Elite Page 43
OVERVIEW OF
HERBAL SUPPLEMENTS
www.elitecme.com.
16. Approximately what percentage of people
worldwide use herbal medicines as some
part of their primary health care?
a. Approximatly 70-80 percent.
b. 40-60 percent.
c. 20-39 percent.
d. 10-19 percent.
17. Which of the following statements
about the regulatory process for herbal
supplements in the United States is false?
a. Herbal supplements are strictly
controlled and must be approved by the
government for effectiveness before
they are marketed.
b. Dietary supplements are not approved
by the FDA for safety and effectiveness
before they are marketed.
c. If an herbal medicine contains a new
ingredient, that ingredient will be
reviewed by FDA before marketing,
but only for safety, not effectiveness.
d. The FDA can take herbal medicines
off the market if they are found to be
unsafe, adulterated, or if the claims on
the products are false and misleading.
18. Which of the following is not a reason
suggested for conficting results on whether
black cohosh helps relieve menopausal
symptoms?
a. Lack of rigor in study design.
b. Overly long study duration (6 months
or more).
c. Use of different amounts of black
cohosh from different sources.
d. Use of different outcome
measures.
19. Which of the following statements about
saw palmetto is false?
a. It may inhibit an enzyme that affects
the level of testosterone, may reduce
the amount of an enzyme that promotes
the growth of prostate cells, and
may shrink the inner lining that puts
pressure on the tubes that carry urine.
b. Data supports the use of saw palmetto
for treating prostate cancer.
c. In most studies, sexual dysfunction was
not a frequently encountered side effect
with use of saw palmetto.
d. Saw palmetto has the same or similar
mechanism of action as fnasteride and
dutasteride, two common drugs used to
treat BPH.
20. Health care practitioners should ask
patients which of the following questions
as part of the medical or medication
history?
a. Are you taking herbal supplements,
vitamins or other over-the-counter
remedies?
b. How long have you been taking any
herbal products and at what dose or
frequency?
c. What, if any, side effects or problems
have you experienced from herbal
medicines?
RPTAZ05HSE13
Page 44 Elite
CHAPTER 5
THE PHARMACY TECHNICIANS
RESPONSIBILITY IN HANDLING
CONTROLLED SUBSTANCES
(4 CONTACT HOURS)
By Bradley Gillespie, PharmD who has over 20 years
experience spanning the regulatory, pharmaceutical
biotech and human nutritional supplement industries.
Author Disclosure: Bradley Gillespie and Elite
0761-9999-13-274-H04-T
666-9053. This lesson is $17.00.
education credit.
Learning objectives
! Understand the depth and breadth of the
problems presented by the abuse of controlled
substances.
! Appreciate the challenges faced by the Drug
Enforcement Administration in its efforts
to safely manage the use of controlled
substances.
! Realize the critical value of a controlled
system of distribution to achieve best
practices in the transactional management of
! Recognize the basic foundations of controlled
substance scheduling.
! Understand all of the processes needed to
manage controlled substances throughout
the drug-use process, as well as know which
DEA form should be used to document each
of the steps.
! Fully understand the requirements of both
paper-based and electronic controlled
substance record-keeping systems.
! Understand the requirements for inventorying
! Appreciate the extent of abuse allowed by the
purveyance of controlled substances over the
Internet, and recognize that there are unique
requirements for such specialized commerce,
separate and apart from that required for
traditional brick and mortar pharmacies.
Why do we need a Controlled Substances
Act (CSA)?
As early as the 1800s, when morphine and
cocaine were discovered, Americans have been
battling the problems caused by drug addiction
and abuse. By the early 1900s, the United States,
in the midst of its frst serious drug epidemic,
began the process of effecting restrictions
designed to limit the availability of opium
and coca. These restrictions were a success,
severely curtailing the unsafe use of many
dangerous drugs. By the time the United States
entered World War II, drug abuse was not even
considered a serious problem.
1

This vacation from drug abuse, though, was
short-lived. By the time the 1960s were under
way, new drugs presenting new challenges,
such as marijuana, various psychedelics and
amphetamines, were all the rage. The government
realized that a new drug-based culture was
developing, and rapidly acted to better understand
and subsequently curb the new problem drugs.
In 1973, the U.S. Drug Enforcement
Administration (DEA) was formed with the
express purpose of enforcing federal drug
laws, with a specifc focus on those with a high
potential for abuse.
1
Although the use of illicit
drugs remains a problem and the mission of DEA
is currently the same, new challenges are now
present in controlling the inappropriate use of
prescription medications. Pharmacy technicians
are in an ideal position to make a positive impact
on this particular problem.
Although any drug can be dangerous if not used
properly, the DEA recognizes that certain drugs
have a higher potential for dependency or abuse.
Further, the agency fully appreciates that while
some dangerous drugs have a legitimate medical
use, many do not, and may be potentially more
dangerous than others.
2

The Controlled Substances Act (CSA) of 1970
was designed as a comprehensive law that
brings together a number of existing regulations
and statutes regulating the manufacture and
distribution of narcotics, anabolic steroids,
depressants, and stimulants, and chemicals used
in the illicit production of controlled substances.
All substances falling under this law are then
categorized based on their medicinal value,
potential to cause harm and their prospect for
abuse and addiction.
3

What is the DEA and what are its
responsibilities?
The primary role of the DEA is to strictly enforce
all federal drug laws. In addition to enforcing
drug laws, DEA also has the mandate to bring
to justice any people or organizations involved
in the growing, manufacture or distribution
of controlled substances. Additionally, DEA
is charged with supporting nonenforcement
programs that are designed to reduce the presence
of illicit controlled substances, both domestically
and internationally. The CSA and its associated
regulations formed its backbone-implementing
Introduction
This pharmacy technician continuing education
course was developed with three key goals in
mind:
It will describe the abuse potential of
controlled substances and the need to apply
more rigorous controls than those required
for other prescription medications.
It will describe the unique challenges for
pharmacy technicians in the management of
controlled substances, from helping with the
proper registration of the pharmacy to allow
for the management of controlled substances,
from ordering, managing, and dispensing
of product to generating and maintaining
adequate records.
It will provide a high level summary of the
federally mandated procedures that have been
put in place to safeguard the drug distribution
of controlled substances, including the
prevention of diversion and abuse.
As practicing pharmacist technicians, it is
critical that we fully realize the potential
hazards associated with the abuse of controlled
substances. All actively practicing pharmacy
technicians who come into contact with
controlled substances must be totally aware
and compliant with all of the laws governing
their practice (which includes the entire cycle
of registration with the Drug Enforcement
Administration, from dispensing controlled
substances to keeping proper records of all
transactions). In addition, because of rapidly
changing technologies, pharmacy technicians
must be aware of laws governing the role of
the Internet in the distribution of controlled
substances.
The controlled substances of choice for abuse
are constantly evolving, just are methods of
diversion. Although the U.S. government is doing
all that it can to keep up with these changes,
pharmacy technicians, on the front line of drug
distribution, are key players in keeping our
society safe and healthy while still providing
the medications needed to treat legitimate
medical issues. To do this to perfection, it is
critical that pharmacy technicians are up-to-
date on all aspects of the Controlled Substances
Act and their responsibilities to make sure that
these potentially hazardous medications are
properly managed throughout the prescribing and
distribution cycle.
Although this course is designed to
be comprehensive and thorough in its
characterization of pharmacy practice as it is
applied to controlled substances, it will not cover
every eventuality that could be encountered.
It also is critical to note that this course was
developed based on applicable federal laws only.
Every knowledgeable and competent pharmacy
technician will also be well-versed in applicable
state-specifc controlled substance laws and
how they apply to their respective practice
settings. For sake of example, some state-specifc
regulations are discussed in the course where
applicable to illustrate potential differences that
may exist between the laws.
Elite Page 45
federal requirements governing the disposition of
both legal and illicit drugs.
4

While the mission of DEA is complex, its
primary responsibilities include the following:
4
Investigating and preparing for prosecution
major violators of controlled substance laws.
Investigating and preparing for prosecution
criminals and drug gangs responsible for
violence and terrorizing of citizens.
Managing a national drug intelligence
program in cooperation with federal, state,
local and foreign offcials.
Seizing for forfeiture assets derived from or
intended to be used for illicit drug traffcking.
Enforcing the provisions of the CSA on the
manufacture, distribution and dispensing of
legally produced controlled substances.
Working with federal, state and local
agencies (as well as foreign governments) to
reduce the availability of illicit drugs of abuse
in the U.S. market through nonenforcement
measures, such as crop eradication, crop
substitution and training.
Coordinating with the U.S. secretary of
state and U.S. ambassadors on all programs
associated with drug law enforcement in
foreign countries.
Liaise with the United Nations, Interpol and
other organizations on matters related to
international drug control programs.
In the context of pharmacy, the DEA has two
major jobs: prevention of the diversion and
abuse of controlled substances, while at the same
time ensuring that the supply of legal controlled
substances remains available to meet legitimate
needs for these drugs. To carry out this important
mission, DEA works hand-in-hand with state,
local and other federal authorities.
5

Controlled Substance Act guidelines
Based on the guidelines laid out in the CSA,
all transactions involving controlled substances
must take place within a closed system of
distribution established by the U.S. Congress. By
defnition, this closed system requires that any
parties that come into contact with a controlled
substance, i.e., the manufacturers, distributors,
prescribers, pharmacies and all others, need to
be fully registered and compliant with DEA
regulations.
Included in that is a requirement that all involved
parties are required to carry out strict accounting
for all controlled substance transactions
(manufacturers batch records, pharmacy orders,
physician prescriptions, dispensing records, and
so on). All such records must be stored separate
from other documents and be maintained in a
format that is readily retrievable.
5
In cases where a state board of pharmacy is
required to revoke the license of a pharmacy,
DEA will typically request that the pharmacy
also surrender its DEA registration. If the
pharmacy should refuse, then DEA would seek
administrative action to revoke the registration.
Less serious infractions of full compliance may
be dealt with through a letter of admonition or an
administrative hearing. In cases where there is
inadequate evidence to justify a full prosecution,
DEA may apply criminal or civil sanctions to
protect public health and safety.
5
Although not part of the CSA, DEA is also
interested in managing the sale of over-
the-counter products containing ephedrine,
phenylpropanolamine and pseudoephedrine,
because these substances can serve as the
starting material in the manufacture of dangerous
amphetamine-like drugs. According to the
Combat Methamphetamine Epidemic Act of
2005, these products are categorized as schedule
listed chemicals (SLCS). The sale of SLCS
is limited to 3.6 grams at a time, requires that
they be locked behind the pharmacy counter,
and that a log be maintained of all purchases.
Monthly sales are limited to 9 grams per month
per purchaser, and each seller is required to
certify that he or she is in compliance with these
requirements.
6
A more detailed description of the Combat
Methamphetamine Epidemic Act of 2005 is
offered below.
What is scheduling?
The CSA lists substances that fell under its
control when the act was put into place in
1970. Additionally, since then, about 160 new
substances have been added, removed or moved
from one schedule to another. To view the
current offcial list, it is likely best to consult the
most current issue of Title 21 Code of Federal
Regulations Part 1300.
7

Controlled substances that ft under the CSA
are currently divided into fve schedules, based
on whether the drug has an acceptable medical
use in the United States, its relative potential
for abuse, and likelihood of causing dependence
when abused. Some examples from each schedule
are listed below:
Schedule I:
Schedule I controlled substances either have
no currently medically acceptable use in the
United States, a lack of accepted safety for use
even if properly medically supervised, or have a
high potential for abuse. Schedule 1 substances
include MPPP, heroin, marijuana, lysergic
acid diethylamide (LSD), peyote, ecstasy and
methaqualone. Additionally, some materials
can be temporarily included in schedule I,
subject to emergency scheduling.
8
Schedule
I controlled substances can be distinguished
from other controlled substances by the fact
that prescriptions for these drugs may not be
written, and these drugs are not easily available
for clinical use.
9
Nonetheless, some of these
compounds are tested in well-controlled clinical
trials under appropriate levels of supervision.
Schedule II:
Controlled substances categorized as schedule II
all have a high potential for abuse and can lead
to severe psychological or physical dependence.
Schedule II narcotics include codeine, morphine,
hydromorphone (Dilaudid), oxycontin
(OxyContin, Percocet), Methadone (Dolphine),
meperidine (Demerol), fentanyl (Sublimaze,
Duragesic), morphine, codeine and opium.
Schedule II stimulants include cocaine,
amphetamine (Dexedrine, Adderal),
ethamphetamine (Desoxyn) and methylphenidate
(Ritalin).
Miscellaneous schedule II controlled substances
include amobarbital, glutethimide and
pentobarbital.
10
Although these drugs do have a
high potential for abuse, because they do have
currently accepted medical uses in the United
States, they can be prescribed with severe
restrictions.
11
Schedule III:
Controlled substances in this schedule generally
are considered to have a potential for abuse
less than substances listed in schedules I or II,
and all have a medically acceptable use in the
United States. The abuse of these drugs may
lead to moderate or low physical dependence
or high psychological dependence. Schedule III
drugs include chlorphentermine, secobarbital,
products containing less than 15 milligrams of
hydrocodone per dosage unit (Vicodin), and
products containing no more than 90 milligrams
of codeine per dosage unit (Tylenol with codeine)
and buprenorphine (Suboxone).
Additional schedule III drugs include
benzphetamine (Didrex), phendimetrazine,
ketamine and anabolic steroids such as Depo-
Testosterone.
12
Schedule IV:
Compared to controlled substances categorized
in schedule II and III, substances in schedule IV
have a low potential for abuse or dependence and
all have a medically acceptable use in the United
States. Schedule IV items include preparations
containing not more than 1 milligram of
difenoxin and not less than 25 micrograms of
atropine sulfate per dosage unit, alprazolam
(Xanax), clonazepam (Klonopin), chlorazepate
(Tranxene), diazepam (valium), lorazepam
(Ativan), midazolam (Versed), temazepam
(Restoril) and triazolam (Halcion), fenfuramine,
pentazocine and sibutramine.
13
Schedule V:
Compared to controlled substances categorized
into schedules I, II, III and IV, substances in
this schedule have a low potential for abuse and
consist primarily of preparations containing
limited quantities of certain narcotics. All
controlled substances categorized as schedule V
have a medically acceptable use in the United
States. In many cases, preparations appearing in
schedule V are used for their antitussive, anti-
diarrheal and analgesic properties. Examples
of schedule V products include preparations
containing not more than 200 milligrams of
codeine per 100 milliliters or per 100 grams
(Robitussin AC, Phenergan with Codeine and
ezogabine).
14
Page 46 Elite
Combat Methamphetamine Epidemic Act
of 2005
Methamphetamine (meth) is a highly addictive,
dangerous and illegal drug. Although there are a
number of chemical processes that can be used
to manufacture methamphetamine, ephedrine,
pseudoephedrine and phenylpropanoloamine,
safe, effective and widely used over-the-counter
medications can be used as starting materials in
the manufacture of methamphetamine.
15
The Combat Methamphetamine Epidemic Act
of 2005 became law in March 2006 and was
effective immediately. This act was designed
primarily to affect persons or establishments
selling products containing ephedrine,
pseudoephedrine and phenylpropanolamine. As
defned in the law, a regulated seller means a
retail distributor (including pharmacies). Further,
the law defnes a retail sale as the purchase of one
of the described products at a retail distributor,
further defned as a grocery store, general
merchandise store, drug store or other entity.
The law sets daily sales limits of ephedrine,
phenylpropanolamine and pseudoephedrine at
3.6 grams per purchaser, without regard to how
many individual sales are transacted, and requires
that all non-liquid forms of these medications be
packaged in 2-unit blister packages whenever
technically possible. Monthly purchases may not
exceed 9 grams per purchaser.
The law also affects sellers who distribute using
mail order. Such distributors are required to
identify the purchaser prior to shipment of the
product and submit mail order reports. Mail
orders are limited to 7.5 grams of medication per
30-day period.
Product placement
Distributors of affected products must place
merchandise in such a way that customers do not
have direct access before completion of the sale
(must be kept behind the counter, or in a locked
cabinet inaccessible to customers).
Logbook provisions
Distributors of affected products are required to
keep a written or electronic logbook of sales that
includes, at a minimum:
Name of product.
Quantity sold.
Names and addresses of buyers.
Date and time of sales.
These logbook requirements apply only to
larger purchases and are not relevant to single
sales of packages containing up to 60 mg of
pseudoephedrine. The distributor may not
complete the sale of the product without frst
checking the buyers government-issued photo
identifcation card. The purchaser is required
to sign the logbook and enter the information
prescribed above.
It is the sellers responsibility to ensure that the
information entered into the logbook is accurate,
based on the identifcation presented. Further,
it is the responsibility of the seller to enter into
the logbook information describing the name of
product and the quantity dispensed.
Lastly, the logbook is required to contain a notice
to purchasers noting that:
Entering false statements or
misrepresentations in the logbook may
subject the purchaser to criminal penalties
under 18 U.S.C. 1001 and such notice must
specify the maximum fne ($250,000.00) and
term of imprisonment (5 years).
The distributor is required to maintain the
logbook with all entries for a period of no less
than two years after the fnal entry was made.
The only purpose of the logbook is to comply
with the provisions of the CSA and to protect
public health and safety (for example, in the case
of a product recall). Any distributor that, in good
faith, releases the contents of their logbook to
federal, state of local law enforcement offcials
is immune from liability for such release unless
it can be proven that such release is shown to be
grossly negligent or a part of willful misconduct.
Self-certifcation and training
Each distributor of affected products must
self-certify that everyone responsible for
delivering such products to consumers has
undergone adequate training to ensure that each
understands the requirements that apply to the
sale of these products. Such self-certifcation
must be submitted to the U.S. attorney general,
and each distributor must retain a copy. Separate
self-certifcations are required for each place of
business in the event that one entity operates
more than one establishment. Copies of the
self-certifcation must be made available to
appropriate federal, state or local offcials, as
requested.
16
Pharmacy registration
Before a pharmacy can legally dispense any
controlled substances, it must go through the
formal process of becoming registered with
the DEA. Registration is accomplished using
a standardized DEA Form 224, which can be
completed on paper or in an online format. When
completing DEA Form 224, the applicant must
be sure to identify all of the drug schedules that
will be dispensed because the registration is
specifc to the prospectively identifed category of
Moreover, the applicant must be fully aware
of any applicable state requirements; federal
registration with DEA does not override state
restrictions or laws. As such, usually applicants
should contact any applicable state licensing
authorities before completing DEA Form 224.
In some states, a state-sanctioned, separate
controlled substances registration number is
required. In that case, this information should be
included in the federal application.
17

However, this sequence may not be appropriate
in all states. For example, the Idaho Board
of Pharmacy suggests frst applying for DEA
registration and then submitting a completed
application for permission to manage controlled
substances to the state.
18
Clearly, best practices
suggest that the applicable laws and regulations
from each state must be researched and closely
followed to ensure appropriate compliance.
After the pharmacy receives DEA registration
allowing it to order and dispense controlled
substances, it will be issued a certifcate of
DEA registration that needs to be displayed in a
prominent location in the vicinity of where the
controlled substances are stored. This certifcate
and all related documents need to be kept
separate from the other pharmacy papers and
readily available for inspection by DEA or any
authorized state or federal offcial.
19
DEA registration is valid for a period of three
years. Within 60 days before the registration
expires, renewal applications are automatically
mailed to the pharmacy. As such, it is critical that
any changes in address are immediately reported
in writing to DEA to ensure proper delivery. The
U.S. Postal Service will not forward renewal
applications. The registration is renewed using
DEA Form 224a. Should the pharmacy move
to a new state, the renewal application should
include a copy of the new state license and state
controlled substance registration.
20

How are controlled substances ordered?
Participation in the process of ordering
medications is a key role of practicing pharmacy
technicians. The procedure for ordering many
medications, including certain schedules III-V
controlled substances, follows procedures similar
to that of ordinary medications. Nonetheless,
the process of ordering schedule II controlled
substances requires specialized processes that
follow a specifc protocol. DEA Form 222 must
be completed to document all orders for schedule
II controlled substances.
Specifc questions that may be encountered by
a pharmacy technician when completing DEA
Form 222 are discussed below.
21
Question: If a wholesaler receives a DEA Form
222 with only minor misspellings in the name or
address of the registrant, can it be accepted?
Answer: Yes. A DEA Form 222 with only minor
typographical errors can be accepted. The DEA
Form 222 is acceptable in cases where there is
no question as to what product is described in the
document, even with misspellings in the name of
the controlled substance.
Question: If certain sections of DEA Form 222
are not flled in by the pharmacy placing the
controlled substance order, can the wholesaler fll
in the missing sections?
Answer: The wholesaler is permitted to fll in
some missing sections. Acceptable sections
include:
Date of the form. The wholesaler may enter
the date on DEA Form 222. If possible, the
date entered should be determined based on
the issue date of the document. The DEA
Form 222 would be considered valid if the
date of issuance is no more than 60 days from
the date of receipt of DEA Form 222 at the
wholesaler.
Elite Page 47
Size of the package. The intended size of
the package cannot be completed by the
wholesaler if omitted by the orderer unless
the specifc product is available in only
one size. In cases where multiple sizes are
available, the wholesaler cannot enter the
package size, and the line item with the
missing package size must be voided.
Strength of the controlled substance.
Analogous to the missing package size
situation, if the controlled substance is
available in only one strength, there is no
requirement to indicate the strength of the
product in the name of drug section of DEA
Form 222. Nonetheless, if the controlled
substance is available in multiple strengths,
then the wholesaler may not provide this
missing information, and the line item with
the missing strength must be voided.
Last line completed. The Last line
completed area of DEA Form 222 must
always be completed by the orderer. If the
orderer should enter an incorrect number in
this section, for example, an incorrect tally
of the total number of packages ordered, the
entire DEA Form 222 is considered invalid
and must be voided.
Question: Are there any circumstances where a
wholesaler can accept a DEA Form 222 when
the size of the container or strength is incorrectly
described on the form?
Answer: In cases where there is no question
about the strength and size of the controlled
substance ordered, it is appropriate for the
wholesaler to accept a DEA Form 222 with such
errors. Nonetheless, if the controlled substance
is available in containers of different sizes or
strengths, then this missing information may not
be provided by the wholesaler, and the line item
with the missing container size or strength must
be voided.
For ordering schedules III-V controlled
substances, documentation similar to that
required for ordering conventional prescription
medications is required. Typically, when ordering
schedules III-V controlled substances, the
pharmacy technician should be sure to maintain
either an invoice or packing slip that documents,
at a minimum, when the products were received,
and confrms the accuracy of the order received
to that placed with the wholesaler. Further, some
additional information must be captured on the
invoice or packing slip, including the actual
name of the controlled substance product, the
formulation type, the total number of containers,
and the number of dosage units per container.
All documents generated describing the order and
receipt of all controlled substances, schedule II-V,
must be maintained using some system that keeps
the documents separate from other pharmacy
papers and in a state that is readily retrievable for
inspection by either DEA or other relevant federal
or state authorities.
5
Storage of controlled substances
Because of the potential for diversion and abuse
of controlled substances, the law is clear in its
description of their storage requirements. The
key elements listed here were abstracted from the
UC-San Diego controlled substances program,
which adheres to the provisions spelled out in the
CSA. They can be kept in mind when developing
a sound and secure storage strategy:
Controlled substances must be stored
according to their schedule number.
Schedule II-V controlled substances must
be kept in a locked cabinet or drawer
that is inaccessible from either above or
below.
The following ancillary equipment must
be installed, according to the following
standards:
Padlock and hinges:
The mounting bolts or screws
attaching the hinges and hasp must be
inaccessible when the door is closed
and the lock is fastened.
Safes and steel cabinet equivalents:
Such containers must either weigh in
excess of 750 pounds or be cemented
or bolted to the foor or wall.
Storage units:
Storage must be adequately secure to
indicate forced entry.
Drawers:
Drawers used to store controlled
substances need to be either the upper
or lower drawers in the stack. The use
of the top drawer is preferred.
It is important to remember that storage facilities
identifed for controlled substances must be used
only for controlled substances, and all contents
must be properly recorded in the applicable
inventory control logbooks. One last thing to
keep in mind is to never transfer controlled
substances from their original container to an
alternative container.
Controlled substance storage facility
access restrictions
When developing standard operating procedures
for managing controlled substances in your
pharmacy, there are several key precautions to
keep in mind.
All access to controlled substances must be
restricted to a prospectively prepared list of
authorized personnel, who must always follow
the following precautions:
Maintain any keys to storage areas in the
physical custody of authorized personnel at
all times.
It is acceptable to produce multiple
copies of keys for assignment to
authorized personnel.
Should an authorized person leave his or her
position at the pharmacy, it is critical to:
Change the combinations on any
applicable combination locks.
Retrieve the authorized individuals keys
prior to departure.
Document the change in personnel in the
applicable inventory log book.
Ensure that the list of authorized
personnel is modifed to omit the
departing persons name.
How to legally transfer controlled
substances
Although schedule II controlled substances
typically are ordered using DEA Form 222 for
sale by the ordering pharmacy, there may be
situations when these controlled substances
need to be transferred to another, properly
registered facility, such as another pharmacy,
the manufacturer or a wholesaler. In such cases,
a DEA Form 222 must also be completed to
document this change in disposition.
In cases where there is a need to transfer
schedules III-V controlled substances between
properly registered facilities, all attributes of the
transfer must be properly documented, either
electronically or in writing. Necessary details
include the following attributes: the date of the
transfer, and the quantity, dosage form, strength
and name of the schedules III-V controlled
substance involved. In addition to these product-
specifc details, the documents must also include
the DEA registration numbers of all involved
parties and their names and addresses.
22

Although certain themes remain constant
between different sorts of transfers, some key
requirements are specifc to the type of transfer.
Transfer of controlled substances
between pharmacies
Should a pharmacy cease operations or change
ownership, it is legal to transfer custody of
its controlled substance inventory to another
properly licensed and registered pharmacy as
long as the following guidelines are followed:
A complete and comprehensive inventory
must be taken on the day of transfer.
Documentation of this inventory must
include the drug name, dosage form, strength,
quantity and date transferred.
A DEA Form 222 or its electronic equivalent
must be generated to document the transfer of
all schedule II controlled substances.
This inventory will form the basis of the fnal
inventory for the pharmacy that is ceasing
operation and transferring custody of controlled
substances. At the same time, this inventory can
serve as the initial inventory of the acquiring
pharmacy. Accurate and complete copies of the
inventory must be included in the records of both
pharmacies. No submission to DEA is required
for this inventory, but it is critical to note that the
inventory documents must be maintained by both
businesses for a period of not less than two years.
Transfer of controlled substances to the
original supplier or manufacturer
Any pharmacy that has custody of a controlled
substance may return it to the original
manufacturer or supplier as long as it is properly
registered with DEA. The pharmacy initiating
the transfer must properly document the transfer.
Proper documentation must include the following
written information:
Page 48 Elite
The date the transfer occurred.
The quantity, strength and dosage form of the
involved controlled substance.
The DEA registration number, name and
address of the supplier or manufacturer who
received the controlled substance.
In the case where schedule II controlled
substances change custody, the offcial record
will be DEA Form 222 or its electronic
equivalent. While no submission to DEA is
required for this inventory, it is critical to note
that the inventory documents must be maintained
by both businesses for a period of not less than
two years.
5
What if controlled substances are lost or
stolen?
DEA is very serious about the management of
controlled substances and considers the theft
or loss of controlled substances a very serious
situation. If a signifcant loss (based on the
discretion of the pharmacy is there a likely
explanation for the loss?) or theft of a controlled
substance occurs at a pharmacy, this needs to be
reported to DEA within one business day.
Theft of a controlled substance constitutes a
criminal event that should also be reported to
the local police and state regulatory authorities,
in addition to notifying DEA. If there is
any question of whether a crime has been
committed, the pharmacy technician should
take a conservative approach, and work with the
pharmacist to properly report the event.
Theft or signifcant loss
The actual circumstances of the signifcant loss
or theft should be documented using DEA Form
106. A completed DEA Form 106 should be sent
to the local DEA division feld offce. Examples
of the information needed to complete DEA
Form 106 include the following items: name
and address of the pharmacy; DEA registration
number; date of the theft or loss; contact
information for any involved law enforcement
offcials; type of theft, any identifying marks on
the labels of the containers involved; and a listing
of all controlled substances missing.
If, after DEA notifcation, it is determined that no
theft or loss occurred, completion of DEA Form
106 is not required. Nonetheless, the pharmacy
must notify DEA of this fact in writing to resolve
the initial report. A copy of submitted DEA Form
106 must be maintained by the issuing pharmacy
for a period of no less than two years.
Although the management of signifcant losses
is similar, regardless of circumstances, some
differences do exist, and are explained in greater
detail below:
In-transit loss
If all or part of an in-transit shipment of a
controlled substance does not arrive at its
intended destination, the responsibility for
reporting this loss falls on the wholesaler. After
the pharmacy has taken custody of the controlled
substance, it is the responsibility of the pharmacy
to report the loss. In either case, the loss is
reported to DEA using DEA Form 106.
Breakage and spillage
From time to time, breakage or spillage of a
controlled substance is expected in the practice
of a pharmacy technician. Such losses do not
constitute a reportable loss. If there is breakage
or spillage, any controlled substance that can
be recovered must be disposed of according
to applicable DEA regulations. Such disposal
must be reported to DEA using DEA Form 41
(Registrants, Inventory of Drugs Surrendered).
A copy of submitted DEA Form 41 must be
maintained by the pharmacy for a period of no
less than two years.
Controlled Substance Registrant
Protection Act of 1984 (CSRPA)
The CSRPA was enacted to provide some
protection to pharmacies registered to distribute
controlled substances. According to the CSRPA,
thefts and robberies of controlled substances can
be federally investigated in some cases if any of
the following conditions are met:
The value of the affected controlled
substances exceeds $500.
Execution of the crime involved interstate or
foreign commerce.
A person was killed or seriously injured as a
result of the crime.
The CSRPA also describes the penalties that may
be applied to perpetrators convicted of violating
its provisions:
5
Burglary or robbery A maximum fne of
$25,000 and/or 20 years imprisonment.
If a dangerous weapon was involved, the
maximum penalty increases to a fne of
$35,000 and/or 25 years imprisonment.
If the crime resulted in death, the penalty
can be as high as a $50,000 fne and/or life
imprisonment.
Unfortunately, theft, including armed robberies,
is occurring at alarming frequency by people
seeking to procure controlled substances for illicit
use. The following case, though, illustrates the
critical role that an alert pharmacy technician can
play in countering such acts.
Police in Wisconsin recently gave credit to
two alert pharmacy technicians for helping to
apprehend a man responsible for a series of
oxycodone thefts and robberies from pharmacies
in Madison, Wisconsin, and surrounding areas.
In this case, the individual entered the pharmacy,
and asked whether a prescription was ready
for another person. A pharmacy technician
answered no, and the man left the store.
Before he was able to leave, though, the two
pharmacy technicians on duty recognized the
man as a suspect in previous thefts from other
area pharmacies. The police were notifed, and
the suspect was arrested outside of the store. The
arresting offcers found knives in his pocket, and
the suspect admitted that he had planned to rob
the pharmacy.
Because of the number of crimes under
investigation, the FBI is participating in the
investigation of the thefts. Local police estimate
that in excess of $87,000 worth of prescription
medications has been stolen in the string of thefts
under investigation, occurring over a period of
approximately four months.
23
What records need to be kept on
controlled substances?
As an underlying philosophy, if a pharmacy
technician should determine that confict exists
within the requirements laid out in federal
versus state requirements for record keeping, the
pharmacy must develop a record keeping system
that is compliant with all applicable laws and
requirements.
Pharmacies need to maintain comprehensive,
complete and current records for each controlled
substance in their inventory. These documents
need to provide full accountability for all
controlled substances from the time that the
controlled substance is ordered until it is
dispensed to the ultimate end user. All such
required records need to be maintained in such
a way that they can be readily retrieved for at
least two years for inspection by DEA or other
authorized federal or state regulators.
All schedule II-related documents must be
kept separate from all other pharmacy papers.
Schedules III-V-related documents may be either
stored separately or in such a way that they can
be readily separated from other business records.
DEA is clear on the defnition of readily
retrievable. Key elements include the following:
Records that are stored electronically or
mechanically must be able to be separated
from other records in a reasonable amount of
time.
They must be able to be readily identifed by
an asterisk, redline or in some other visually
identifable manner.
Controlled substance documents that must be
maintained by a pharmacy include:
DEA Form 222 (paper or electronic
equivalent) for all schedule II controlled
substances.
Power of attorney authorization describing
who can sign forms.
Any receipts or invoices involved in the
procurement of schedules III-V controlled
substances.
All inventory records of controlled
substances.
Any record of controlled substance transfers
between registered facilities.
Records of any dispensing of controlled
substances.
Reports of any theft or signifcant loss of
controlled substances (DEA Form 106, when
applicable).
Inventory of drugs surrendered (DEA Form
41, when applicable).
DEA registration certifcate.
Self-certifcation certifcate or logbook
documenting adherence to the Combat
Methamphetamine Epidemic Act of 2005.
Prescription records
DEA does not stipulate whether pharmacies
should maintain their prescription records using
either an electronic or paper-based system.
Elite Page 49
The correct system for each pharmacy will be
determined by the specifcs of its operation and
the preference of the operator. Nonetheless, there
are few central themes to keep in mind when
selecting a record-keeping system:
All systems must accommodate both federal
and state requirements.
All prescription records must be kept in a
format that makes them readily retrievable by
DEA and state authorities.
Pharmacies have three different options to satisfy
DEA record-keeping requirements:
Paper option 1 (three separate fles)
A separate fle describing all schedule II
controlled substances dispensed.
A separate fle describing all schedules
III-V controlled substances dispensed.
A separate fle for all non-controlled
substances dispensed.
Paper option 2 (two separate fles)
A separate fle for all schedule II
controlled substances dispensed.
A separate fle for all other drugs
(schedules III-V controlled substances
and uncontrolled substances). If this
approach is adopted, then all controlled
substance prescriptions must be marked
with a red C stamp at least one inch
high.
Electronic prescription records (Option 3)
Key elements of electronic record keeping
systems include:
In cases where a prescription is created,
signed, transmitted and received
electronically, all records related to that
prescription need to be maintained by the
pharmacy electronically.
All electronic records for a prescription
need to be kept for at least two years
from either the date they were created or
received by the pharmacy. It is important
to remember that this record retention
time may be superseded either at present
or in the future by applicable federal or
state law.
Controlled substance records need to be
readily retrievable from all other records.
Electronic controlled substance records
must be either easily readable or rendered
into a format that any person can read.
All electronic record keeping systems
need to be maintained in a manner
meeting the requirements spelled out in
21 C.F.R. 1311.
Although the records can be maintained
on computers or servers that are remotely
located, the records must be readily
retrievable at the registered location upon
request of DEA or other law enforcement
offcials.
Electronic copies of prescription records
must be sortable by prescriber name,
patient name, drug dispensed and date
flled.
5
Pharmacy technicians, especially after
completing this course, certainly are aware of
the importance of complying with all aspects of
the CSA, including record keeping. Nonetheless,
to reinforce the seriousness of DEA and its
treatment of the law, it is useful to consider the
recent (April 2013) settlement reached between
CVS Pharmacy and DEA.
CVS agreed to pay an $11 million penalty to
settle claims made against it for record-keeping
violations under the CSA. According to a DEA
press release, CVS violated the CSA and record-
keeping regulations by:
1. The creation, entry and maintenance of
dummy DEA registration numbers for
prescribers on dispensing records, some of
which were subsequently provided to state
prescription monitoring programs.
2. Dispensing prescriptions for prescribers with
invalid DEA registration numbers.
3. Entering and maintaining store records,
including prescription bottle labels containing
DEA registration numbers of non-prescribing
practitioners, instead of the DEA registration
numbers of the actual prescriber.
Although CVS was not required to admit liability,
and the government did nothing to concede the
legitimacy of its claims, CVS did acknowledge
publicly that each of its DEA-registered stores is
required to comply with CSA-mandated record-
keeping requirements as well as any regulations
that may be implemented in the future.
24
All of the CSA violations that CVS was accused
of are well within the practice scope of pharmacy
technicians. As such, an astute pharmacy
technician serves in an ideal role to help ensure
that his or her practice remains compliant with all
applicable laws.
What are the inventory requirements for
controlled substances?
One task in which pharmacy technicians play
an integral role is inventorying controlled
substances. By defnition, an inventory is a
comprehensive, complete and accurate listing
of all forms of controlled substances in the
possession of the DEA-registered pharmacy.
The method of inventorying varies by type and
bottle size of controlled substance. An actual,
physical count is required of all medications
categorized as schedule II controlled substances.
Actual counts also are required for schedules
III-V controlled substances contained in bottles
holding more than 1,000 dosage units. For
smaller containers of schedules III-V controlled
substances, an estimated count will suffce.
The CSA mandates that all documents of
inventory activities be maintained within a
registered location in a readily retrievable manner
for a period of no less than two years. Further,
all documents on the inventory of schedule II
controlled substances must be kept separate
from documents from the inventory of all other
The CSA describes multiple types of inventories.
Different inventories include the following:
Initial inventory
When an initial DEA registration is granted, the
pharmacy is required to conduct what is called
an initial inventory. The initial inventory is a
count of every controlled substance (regardless
of schedule) in its possession (either actual, or
estimated, as described above). Even in cases
where there are not yet any controlled substances
in its possession, the pharmacy must still
complete the required documentation, showing a
zero inventory.
While there is no stipulation that the inventory
be submitted to DEA, the Code of Federal
Regulations does provide an outline of the
information that needs to be included in the initial
inventory documentation. Key elements include:
The date that the inventory was conducted.
A statement of what time of day the inventory
was conducted, at the start or close of
business.
The descriptive name of each controlled
substance inventoried.
The formulation of each controlled substance
inventoried, for example, 20 mg tablet.
The size of each container, i.e., the number
of dosage units per container, for example, a
1,000-tablet bottle.
The number of containers of each fnished
form, for example, number: 6; 50-tablet
bottles.
A count of each controlled substance in
possession of the pharmacy (count to be
conducted as described above).
Although not required, DEA suggests that
inventory record documents include the DEA
registration number name, address of the
pharmacy, and the signature of the person
ultimately responsible for the conduct of the
inventory.
Biennial inventory
Following the initial inventory, each pharmacy
registered to dispense controlled substances is
required to take a biennial (every two years)
inventory. All of the information required for
the initial inventory is required for the biennial
inventory. While the exact date of the biennial
inventory is not described in the CSA, it
must occur within two years of the previous
inventory. As with the initial inventory, there is
no requirement to submit inventory documents
to DEA, although they must be maintained in a
readily retrievable state for a period of no less
than two years.
Newly scheduled controlled substance
inventory
On some occasions, a drug that was not
previously scheduled is scheduled. In other cases,
a controlled substance can be re-scheduled.
Should either of these occur, an inventory (with
the count completed, as described above) needs
to be conducted as of the effective date of re-
scheduling or initial scheduling. As with initial
and biennial inventories, all related documents
Page 50 Elite
must be maintained in a readily retrievable state
for a period of no less than two years.
5
What are the prescription requirements
for controlled substances?
Although there are similarities between
prescription format and requirements for
controlled substances and ordinary prescriptions,
the astute pharmacy technician will be aware of
several attributes unique to orders for controlled
substances. Key ideas to keep in mind are
described below.
Schedule II controlled substances
Except in cases where directly dispensed by the
practitioner (non-pharmacist) to the ultimate
patient, schedule II controlled substances may
not be dispensed without the written prescription
of an authorized practitioner except in certain
emergency situations. In such circumstances,
schedule II controlled substances can be
dispensed as a result of an oral prescription,
provided that the oral prescription is followed up
with a complete written prescription within seven
calendar days. Reflls are never permitted for
prescriptions written for schedule II controlled
substances.
5
Schedule III and IV controlled substances
Except in cases where directly dispensed
by the practitioner (non-pharmacist) to the
ultimate patient, schedule III and IV controlled
substances may be dispensed with a written or
oral prescription (if the prescription is given
by an oral order, it shall be promptly reduced
to a written format by the pharmacist
25
). Such
prescriptions may not be flled or reflled
more than six months after the date that the
prescription was originally written. Moreover,
the prescription may not be reflled more than
fve times after the original flling unless properly
renewed by the prescriber.
5
Schedule V controlled substances
No schedule V controlled substances may ever
be dispensed for any reason other than for a
medically valid use.
5
Non-prescription drugs with the potential
for abuse
If it ever appears to the U.S. attorney general that
a drug not considered a prescription drug should
be considered as such because of its potential
for abuse, he or she shall advise the secretary of
Health and Human Services to furnish his or her
offce with all available, relevant data to make
this determination.
5
Controlled substances and the Internet
No controlled substance that is a prescription
drug shall be delivered, distributed or dispensed
by means of the Internet without a valid
prescription (same prescription requirements as
for a brick and mortar pharmacy). A prescription
is considered valid if the following requirements
are met:
5
The prescription is issued for a legitimate
medical purpose in the usual course of
professional practice.
The prescriber has conducted at least one
in-person medical evaluation of the patient
or is a covering practitioner for another
practitioner who has conducted such an
evaluation.
An in-person medical evaluation is defned as
a medical evaluation that is conducted with
the patient in the physical presence of the
practitioner.
The dispensing of a controlled substance
is pursuant to regulations consistent with
effective controls against diversion.
26
If a pharmacy technician has any concern about
the validity of a prescription for a controlled
substance, he or she has an obligation to bring
these concerns to the attention of the pharmacist
on duty at that time. Pharmacy technicians should
be aware that to fll a questionable prescription
for a controlled substance might be interpreted as
a felony offense.
27
Faxed prescriptions for controlled
substances
Prescriptions received by fax are never valid
for schedule II controlled substances. However,
prescriptions for schedules III-V controlled
substances may be transmitted by fax from the
prescriber or a prescribers agent and received
by the dispensing pharmacy. In this case, the
faxed prescription is considered equivalent to the
original prescription, as long as the prescriber
has manually signed the prescription (prior to
faxing).
5
Telephone prescription of controlled
substances
The only time that a schedule II controlled
substance can be prescribed by telephone is
in certain emergency situations, as described
previously. With schedules III-V controlled
substances, a pharmacy can dispense based on
an oral prescription, provided that it is promptly
reduced to a written form before dispensing.
All of the information required for a written
prescription must be collected for an oral
prescription, of course, without the signature of
the prescriber.
5
Transfer of schedules III-V prescription
information
If a pharmacy is properly registered with the
DEA, it may transfer original prescription
information for schedules III-V controlled
substances to another properly DEA registered
pharmacy for the purpose of refll dispensing
on a once-only basis. However, if pharmacies
are electronically linked with a real-time, online
database, the transfers may occur up to the
maximum number of reflls permitted by the
prescribers authorization.
Transfers of controlled substance prescriptions
are tightly controlled and subject to a number of
requirements, including:
The transfer communication must not involve
a pharmacy technician; the conversation
must be between two registered pharmacists.
The pharmacy technician should, though, be
aware of the transfer requirements.
The word VOID must be written on
the face of the invalidated prescription. If
the prescription is electronic, the original
database must somehow be notated to
describe the transfer of the prescription.
On the reverse side of the invalidated
prescription, the following information
should be included: DEA registration of
the gaining pharmacy, the name of the
pharmacist receiving the information, and the
name and address of the receiving pharmacy.
With electronic prescriptions, similar
information must be added to the prescription
record.
The name of the transferring pharmacist and
the date of transfer must be recorded.
With paper prescriptions, the word
TRANSFER must be written on the face
of the transferred prescription, and all of the
information required to be on an original
prescription must be collected.
When multiple pharmacies access the same
prescription records from a shared database,
they must satisfy all of the requirements of a
manual prescription refll using their shared
electronic system.
5
In addition to the many details outlined above,
the use of electronic pharmacy systems to
facilitate the issuance of prescriptions for
controlled substances is allowed only after the
system has completed a successful third-party
audit or certifcation review. This review or audit
must conclude that the entire application meets
DEA requirements for electronic systems.
5
Do controlled substances have any special
dispensing requirements?
Components of the prescription label for
controlled substances are not hugely different
than those used for other prescription
medications. The differences that are necessary to
be aware of when handling controlled substances
are more closely related to the act of dispensing.
A few key elements for the pharmacy technician
to keep in mind are:
Controlled substances may be received from
the pharmacy only by the patient or a member
of the patients immediate household.
Schedule II controlled substances can be
dispensed only when a written prescription is
presented to the pharmacy, accept in certain
bona fde emergency situations. If an oral
prescription is accepted in response to a bona
fde emergency, a full, written prescription
must be presented to the pharmacy within
seven days.
With schedules III-V controlled substances,
the prescriptions can be delivered to the
pharmacy in a variety of formats, including
paper, fax, orally or electronically, as long as
the prescription meets the applicable DEA
requirements for the prescription.
5
Multiple prescriptions for schedule II
The complexities of DEA regulations designed
to counter diversion create a number of
Elite Page 51
complications that pharmacy technicians may
encounter when working with prescriptions
for controlled substances. One key issue is the
frequency of how often a patient physically
meets with his or her prescriber. A number of
patients are relatively stable. As such, they have
no need to meet with their prescriber on a regular
basis. In these cases, there is no need to schedule
a monthly appointment. Because the CSA
requires that a physical visit is required to issue
a controlled substance prescription, this situation
creates a problem.
28
The provision of single prescription for a large
quantity of a controlled substance to be flled at
one time is not viable: insurance companies may
not cover more than one month at a time, and to
prevent diversion, it is not a good idea to release
large amounts of a controlled substance within a
community.
DEA regulations require that schedule II
controlled substances cannot be partially flled,
and the prescriptions cannot be post-dated. What
this means is that it may become quite diffcult
for chronically ill but stable patients to receive
their controlled substance medications on a
regular basis.
28
In response to this problem, prescribers and
pharmacists worked together to develop a
work-around approach. Typically, the prescriber
generates a series of prescriptions, allowing for a
constant supply of the controlled substance that
are issued to the patient, with the directions to the
pharmacy to dispense the prescriptions only one
at a time. These instructions are usually spelled
out within the prescriptions.
For example, in a case where a prescriber wishes
to provide his or her patient with a 90-day supply
of a schedule II controlled substance, instead of
writing a 90-day supply, three prescriptions, each
providing a 30-day supply, would be generated.
All three prescriptions would be dated the same:
the date of issuance. The following notations
would be included:
First prescription no additional notation.
Second prescription includes the directive:
Do not dispense until 30 days after the frst
prescription was flled.
Third prescription includes the directive:
Do not dispense until 60 days after the frst
prescription was flled and 30 days after the
second prescription was flled.
This practice was subsequently approved by DEA
in the 1990s and published in 2004.
29
Shortly
after, though, this document was withdrawn for
unrelated reasons, leaving patients, pharmacies
and prescribers without a good way to provide
ongoing controlled substance therapy.
28
In 2007, DEA adopted new rules clarifying how
the practice could be legally accomplished.
Key elements of Section 1306.12, Reflling
prescriptions; Issuance of multiple prescriptions,
are described below:
The reflling of a schedule II controlled
substance is prohibited.
Prescribers may issue multiple prescriptions
allowing a patient to receive a total of a
90-day supply of a schedule II controlled
substance, provided that the following
conditions are met:
Each separate prescription must be for
a valid medical use by an individual
prescriber acting in the course of his or
her normal practice.
The prescriber provides complete
instructions on each prescription,
indicating the earliest date that the
pharmacy can fll the prescription.
The prescriber can conclude that the
provision of multiple prescriptions to a
patient does not create an unnecessary
risk of diversion or abuse.
The issuance of multiple prescriptions
is not counter to applicable state or local
laws.
The prescriber is fully compliant with all
other applicable requirements as spelled
out in the CSA.
Nothing in these new rules shall be
considered to mandate or encourage
individual prescribers to issue multiple
prescriptions or to limit their patient visits
to every 90 days. It is incumbent on the
prescriber to determine, in accordance
with good medical practice, whether it is
appropriate to issue multiple prescriptions
and how often they should see their patients.
30
These new rules provide a good deal of fexibility
for prescribers and pharmacies to optimize the
supply of controlled substances to their patients.
It provides no limitation on the number of dosage
units that can be dispensed at a time. The only
stated limitation is that no more than a 90-day
supply can be authorized at any one time.
28
While
this is a positive in that it codifes a practice that
pharmacies have used for many years to best
serve their patients, its leeway also creates a
high level of responsibility for the pharmacy to
prevent potential abuse and diversion.
This creates an ideal opportunity for pharmacy
technicians to augment patient care. An astute
pharmacy technician will become acutely aware
of the applicable rules, laws and guidelines, and
work alongside the pharmacist on duty to ensure
that no laws are broken while still providing
optimum care to their patients.
The Secure and Responsible Drug Disposal
Act of 2010
Although there is an expectation that all
dispensed prescriptions will be used by the
prescribed patient in the manner intended, the
reality is that in many cases, after the medical
condition is resolved, excess medication will be
left over. Certainly this is no different in the case
of controlled substances.
Historically, the recommendation was to simply
fush the unwanted medications down the toilet.
This approach has been challenged because of the
pollution that it causes in streams, lakes, rivers,
and our domestic water supply.
Finding a way to safely dispose of unused or
expired medications has been and still is a
recurrent challenge. Because of the potential for
abuse, this can be an even greater problem with
To do nothing encourages the most common
form of controlled substance diversion: theft
of medications from the intended patients
medicine cabinet.
31
It seems obvious that at the
time controlled substances are no longer needed,
they should be removed and placed somewhere
out of reach of someone who might abuse them
or be harmed by them. This is an excellent
opportunity for pharmacy technicians to provide
valuable input that can help keep people safe by
controlling the disposition of unneeded controlled
substances.
The DEA position is clear: Except in certain
situations described below, it forbids the
collection of expired or unused controlled
substances by pharmacies,
32
and in most cases,
this practice is also forbidden by applicable state
regulations.
Even though it is clearly illegal, it is also
probably a bad practice to consider. Most
pharmacies would want to avoid it because of the
increased security risks that it would create and
the logistical challenges associated with keeping
the old controlled substances separate from
the normal inventory. And it could create the
appearance for some patients that the pharmacy is
dispensing returned or used medications.
28
DEA recognized that there was a lack of suitable
methods to dispose of expired or unused
medications. In response, DEA has sponsored
the National Take Back Initiative and also
organizes the twice-yearly National Prescription
Drug Take Back Days.
33
Both of these events,
coordinated by local law enforcement and DEA,
and are designed to provide an easy approach for
people to discard unneeded controlled substances
and other medications. Participation in such
events is an excellent opportunity for pharmacy
technicians to get involved and contribute to the
good health of their patients.
Although the above-mentioned projects serve
as great starting points, it is thought that there
is still plenty of work to be done. Lawmakers
were startled to learn of the increases in deaths
from the abuse of prescription opioids, which
had increased a total of 14 percent between the
years 2001 and 2005. At the same time, the topic
of water pollution in U.S. waterways as a result
of fushing medications down the toilet was a
constant topic of debate.
In an attempt to remediate these issues, the
Secure and Responsible Drug Disposal Act was
passed in 2010.
34
The passage of law provides
the opportunity for DEA registrants, such as
pharmacies, to accept unneeded controlled
substances that have been returned by patients
who have legally received them.
Page 52 Elite
Key elements of the 2010 law are:
Anyone who has lawful possession of a
controlled substance can deliver to another
person the controlled substance for the
purpose of disposal, provided that the
following requirements are met:
The person receiving the controlled
substance is properly authorized to
receive the controlled substance.
The act of disposing of the controlled
substance is accomplished in accordance
with the relevant regulations as issued by
the attorney general to prevent diversion
of the controlled substance.
When developing related programs, the
attorney general will need to weigh the
beneft to public health and safety against the
practicality and cost of participation. As such,
this law or related regulations do not require
pharmacies to establish or operate a disposal
program.
The law authorizes, by regulation, certain
long-term care facilities to dispose of
controlled substances on behalf of their
patients, so long as it is accomplished in a
manner consistent with public health and
safety.
Should a patient die while in possession of
controlled substances, any person entitled by
law to dispose of the deceaseds property can
deliver the unneeded controlled substance to
another person authorized to take delivery of
the product, as described in this law.
35
Internet pharmacies and the dispensing
of controlled substances
As previously discussed, federal laws have
been enacted prohibiting the sale of schedule
II-V controlled substances without a valid
prescription stemming from a proper prescriber/
patient relationship. According to most state
laws, this requires, at a minimum, a physical
examination. This requirement frequently
impacts the sale of controlled substances over the
Internet. According to current laws, the practice
of cyber doctoring, which often relies on a
review of patient-reported questionnaires, is not a
legitimate practice.
36
Before the passage of the Ryan Haight Online
Pharmacy Consumer Protection Act of 2008,
federal laws on Internet pharmacies remained
somewhat vague. The passage of this law makes
matters very clear and easy to understand. The
gray areas have been removed, identifying which
aspects of practice are legal and which are illegal.
Ryan Haight is intended to stop the so-called
rogue Internet sites, but applies to all online
pharmacies that provide controlled substances.
37
Ryan Haight specifcally relates to controlled
substances and has no bearing on medications
that are not scheduled. Under this law, it is
now illegal to deliver, dispense or distribute a
controlled substance over the Internet unless the
online pharmacy is the holder of a modifed DEA
registration that allows it to operate as an online
pharmacy. As a result of this law, any person
who dispenses a controlled substance without the
proper DEA-issued credential is in violation of
federal law and subject to criminal prosecution
and loss of DEA registration.
28
By defnition provided in Ryan Haight, an online
pharmacy is any person, entity or Internet domain
in the United States or elsewhere that knowingly
or intentionally distributes or dispenses a
controlled substance using the Internet. Potential
examples of an online pharmacy include:
A website that offers to sell or sells any
controlled substance or a prescription for
obtaining a controlled substance to any
person in the United States.
Any person who operates a website as
described above.
Anyone who pays or offers to pay a
prescriber to generate prescriptions for
controlled substances for customers of a
website.
Anyone who pays a pharmacy to dispense
a controlled substance prescription that was
issued to a customer of a website.
Any person who sends an email that:
Proposes to sell a prescription for a
controlled substance or a controlled
substance in any manner not authorized
by the CSA.
Directs buyers to any website that is
operated in violation of any provisions of
the CSA.
Leads to the delivery, distribution or
dispensation of a controlled substance in
any way violating the provisions of the
CSA.
Any pharmacy that meets the defnition of
an online pharmacy as described above is
not exempt from the CSA and must meet the
increased regulation as described in Ryan
Haight.
28
Nonetheless, some pharmacy websites may be
exempt from Ryan Haight in some circumstances.
An exemption can be obtained if its Internet-
facilitated activity with controlled substances is
limited to flling new or reflling schedules III-V
controlled substances. While it is possible, then,
to obtain an exemption from Ryan Haight, it is
critical that pharmacy technicians are clear on
the defnition of flling a new prescription for
controlled substances as well as reflling a new
prescription for controlled substances.
28
According to the provisions of Ryan Haight,
flling new prescriptions for controlled substances
in schedules III-V means flling a prescription if
the following conditions are met:
The dispensing pharmacy has previously
dispensed to the same patient the same
controlled substance using non-Internet
means, supported by a valid prescriptions
from a DEA-authorized prescriber.
The pharmacy requests from the prescriber
authorization to issue a new prescription for
that same patient.
The prescriber, in the course of practice
ordinary to his or her specialty, determines
that there is a legitimate medical purpose to
issue the new prescription.
39
According to the provisions of Ryan Haight,
reflling prescriptions for controlled substances in
schedules III-V means flling a prescription if the
following conditions are met:
The dispensing of a schedules III-V
controlled substance must be in accordance
with the prescriber-directed refll instructions
as part of a legitimate prescription meeting
DEA requirements.
The prescription is not a new prescription to
an individual for a controlled substance that
was previously prescribed.
39
In summary, Ryan Haight was written and
enacted with the intention of controlling the
dispensing of controlled substances over the
Internet to reduce their potential for abuse and
diversion. Operating counter to this act is a direct
violation of 21 U.S.C. 841(h)(1), and subject to
potential criminal prosecution.
40
DEA is serious about putting its enforcement
muscle behind Ryan Haight.
In March 2013, United Parcel Service (UPS)
entered into an agreement with the United
States Attorneys Offce for the Northern
District of California, in which UPS agreed
to forfeit $40 million in payments that it had
received from illicit pharmacies. UPS agreed
to implement a compliance program to make
sure that illegal online pharmacies will not
be able to use their services to distribute
drugs. In describing this settlement, DEA was
hopeful that it would send a message to other
shipping frms that they need to put public
health and safety ahead of profts.
41
Summary and conclusions
Many of the drugs that are now called controlled
substances have had abuse problems in the
United States for more than 200 years. Over the
course of the past 100 years, the U.S. government
has taken various approaches to try to control
such abuse.
In 1970, the government passed the Controlled
Substances Act (CSA), a concerted effort to
fnally bring the problem under control. The U.S.
government also established an independent
agency, the Drug Enforcement Administration
(DEA) to strictly enforce drug laws, including
the CSA. Drugs that fall under the CSA are
divided into fve separate schedules based on
the substances potential for abuse as well the
likelihood of it causing dependence.
To legally manage controlled substances, it is
critical that pharmacy technicians master the
requirements for ordering, transferring, record
keeping, inventorying, prescription requirements,
dispensing and disposal of controlled substances.
In addition, pharmacy technicians should also
be aware of what needs to be done to report
a signifcant loss of a controlled substance as
well specifc registrational and operational
requirements for Internet pharmacies dealing with
Elite Page 53
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THE PHARMACY TECHNICIANS
RESPONSIBILITY IN HANDLING
CONTROLLED SUBSTANCES
www.elitecme.com.
21. Which of the following controlled
substances is included in schedule IV of
the CSA?
a. Oxycodone.
b. Clonazepam.
c. Acetaminophen with codeine.
d. Ketamine.
22. Any pharmacy that has custody of a
controlled substance may return it to
the original manufacturer or supplier, as
long as it is registered with DEA. The
pharmacy initiating the transfer must
properly document the transfer. Proper
documentation must include all of the
following written information, except:
a. The date the transfer occurred.
b. The quantity, strength and dosage form
of the involved controlled substance.
c. The date that the pharmacy took
original custody of the controlled
substance.
d. The DEA registration number,
name and address of the supplier
or manufacturer who received the
controlled substance.
23. The Code of Federal Regulations provides
an outline of the information that needs to
be included in controlled substances initial
inventory documentation. Key elements
include which of the following?
a. The descriptive name of each
controlled substance inventoried.
b. The formulation of each controlled
substance inventoried, for example,
20 mg tablet.
c. The size of each container, i.e., the
number of dosage units/container, for
example, a 1,000-tablet bottle.
24. According to DEA, prescribers may issue
multiple prescriptions allowing a patient
to receive a total of a 90-day supply of
a schedule II controlled substance when
which of is true?
a. The prescriber can conclude that the
provision of multiple prescriptions to a
patient does not create an unnecessary
risk of diversion or abuse.
b. The issuance of multiple prescriptions
is supported by at least one set of laws:
federal or state.
c. Complete instructions are provided
on at least one of the prescriptions
indicating the earliest date that the
pharmacy can fll the prescription.
d. The prescriber need not be concerned
that the provision of multiple
prescriptions to a patient creates an
unnecessary risk of diversion; he or
she must only be clear that it does not
create an unnecessary risk of abuse.
25. According to the provisions of the
Ryan Haight Act of 2008, flling new
prescriptions for controlled substances in
schedules III-V means flling a prescription
when which of the following conditions
are met?
a. The dispensing pharmacy has
previously dispensed to the same
patient the same controlled substance,
using non-Internet means, supported
by valid prescriptions from a DEA-
authorized prescriber.
b. The prescriber does not issue a new
prescription for that same patient.
c. The pharmacy technician determines
that the there is a legitimate medical
purpose to issue the new prescription.
d. The patient is personally known to the
pharmacist or pharmacy technician
flling the prescription.
RPTAZ04CSE13
Page 54 Elite
CHAPTER 6
THE PHARMACY TECHNICIANS ROLE IN
REDUCING MEDICATION ERRORS
(2 CONTACT HOURS)
By Katie Ingersoll, RPh, Pharm D and staff pharmacist
for national chain.
0761-9999-13-245-H05-T
666-9053. This lesson is $10.00.
education credit.
Learning objectives
! Explain the common points of medication
errors as they pertain to pharmacy
technicians.
! Discuss strategies to prevent and reduce the
occurrence of medication errors.
! Identify the eight rights of medication
administration.
! Describe important patient safety
considerations.
! Identify the components of a root-cause
analysis.
! Explain continuing education interventions
that help reduce medication errors.
Introduction
Pharmacy technicians play a major role in the
safe distribution of medications. They have a
multitude of responsibilities that may include:
6
Interpreting written prescriptions.
Performing pharmacy calculations.
Inputting patient and prescription data into
the computer.
Managing inventory.
Filling and labeling prescription bottles.
Helping to resolve issues with insurance
companies.
The pharmacy technicians role continues to
evolve and varies considerably, depending on the
practice setting (e.g., retail pharmacy, inpatient
hospital) and the state in which the technician
practices.
10
Ultimately, regardless of setting or
entering information on the wrong patient
record, or failure to enter known health
care issues such as pregnancy.
3, 5
Knowing
as much as possible about the patients
condition helps to reduce the possibility of
such errors.
Order entry: Errors at this point are usually
associated with missing or incorrect drug
information. Research indicates that more
than one in 10 medication errors are directly
associated with the use of incorrect drug
names, misunderstood abbreviations, and
illegible or vaguely written orders. Errors
also occur despite computer safety features,
such as drug alerts. Such alerts can be
lengthy and numerous, and sometimes busy
technicians override an alert to save time
and trouble. However all alerts and clinical
warnings should be relayed to and discussed
with the pharmacist. Such communication
is essential to accurate dispensing of
medications and the safety of the patient.
3,5
Filling and dispensing: About 80 percent
of dispensing errors are related to incorrect
selection of the medication from stock.
This may be due to look-alike/sound-alike
medication names or look-alike packaging.
For example, a pharmacy technician may
select a medication container because of
past familiarity with a label, the size or
shape of the container, or even the location
of the container. This is especially common
if the technician is in a hurry or has been
accustomed to a drug being packaged in a
particular way or located in a certain area.
3,5
Accuracy check: The accuracy check is
always performed by a pharmacist, never
by a pharmacy technician. During an
accuracy check, the pharmacist checks the
exactness and correctness of the flling
process. Sometimes this check is performed
incorrectly, especially if the person
performing the steps involved in flling and
dispensing is the same person who performs
the accuracy check. It is recommended that,
whenever possible, a person other than the
one who performs the flling/dispensing
process should carry out the accuracy check.
In this way, an independent double-check is
conducted.
3
Point of sale: Sometimes a prescription
that has been accurately flled is given to a
patient for whom it was not intended. A busy
outpatient setting is an environment in which
it can be relatively easy to give medication to
the wrong patient. It is recommended that the
person picking up the prescription verify the
address or another identifer in addition to the
name of the patient.
3,5
Patient education: It is estimated that
approximately 80 percent of medication
errors can be identifed during the patient
education process. Simply asking whether a
patient has any questions is insuffcient a
conversation with the patient to assess the
persons knowledge of the prescription is
necessary. Research also shows that patient
location, the goal is for the pharmacy technician
to provide an extra layer of safety, for the
safety and well-being of patients.
5
Medication errors
What is a medication error? According to the
National Coordinating Council for Medication
publication of reports from nationally renowned
experts, including the 2006 report by the Institute
of Medicine, medication errors cause harm to
about 1.5 million patients every year.
10
Sadly,
it is estimated that at least 44,000 deaths occur
every year as a consequence of medication
errors.
1
Millions more errors are stopped before
administration to a patient. In addition to patient
harm, medication errors have a signifcant
monetary impact. Such errors are estimated to
cost billions of dollars annually in additional
treatment costs.
10

Barbara is a pharmacy technician who works
in the pharmacy of a small community hospital.
As she returns to the pharmacy after lunch, she
encounters a nurse from one of the medical/
surgical units. The nurse tells Barbara that the
unit is unbelievable today. A couple of Dr.
Morrisons patients arent doing well, and two
nurses called in sick. Will you check on some
of Dr. Morrisons orders we just sent to you?
We need that furosemide right away. One of his
patients has some mild congestive heart failure
and we need to deal with it quickly!
Barbara hurries into the pharmacy and fnds an
order from Dr. Morrison to be flled immediately.
The order is for furosemide for Janice Brady.
Barbara is puzzled. She remembers flling an
order for analgesia for Ms. Brady earlier in
the day. But Ms. Brady is 24 years old and
hospitalized for surgical repair of several
compound fractures following an automobile
accident.
Barbara calls the unit and fnds that the
furosemide was intended for a Ms. Janine
Brady, an 82-year-old woman hospitalized with
pneumonia. Dr. Morrison had documented the
order on the wrong medical record, and the nurse
who transcribed the order had been pulled from
another unit and was not familiar with either
patient. To add to the problem, the two women
share the same last name and similar frst names.
Thanks to Barbaras alertness, an error was
prevented.
There are countless reasons why medication
errors occur. Short staffng, inattention to detail,
similar names of patients, and similar names of
medications all contribute to medication errors.
Although pharmacists are ultimately responsible
for all dispensed prescriptions, pharmacy
technicians are an essential part of the process of
safely flling and dispensing medications.
3

What are the common points of medication errors
as they pertain to pharmacy technicians?
Prescription drop-off: Errors at this point
are most often linked to either missing or
inaccurate patient information. Examples
include failure to enter known drug allergies,
Elite Page 55
education and error prevention strategies are
especially important when high-alert drugs
are being dispensed.
3
Ongoing vigilance and alertness are necessary
at all points of potential error to ensure accuracy
of drug dispensing and patient safety. Pharmacy
policies and procedures must be evaluated on
a regular basis to identify causes of potential
breakdowns in accuracy and safety.
Strategies for error reduction and
prevention
Martin, a pharmacy technician, works in the
pharmacy of a large drug store. As soon as the
pharmacy opens, there is a long line of impatient
customers who need prescriptions flled or
reflled. Martin attempts to read a prescription in
handwriting that is diffcult to read. He believes
that he has interpreted it correctly and proceeds to
fll the prescription for Actos, 35 mg once daily.
He asks the pharmacist to perform an accuracy
check, saying, Here is Mrs. Dellers diabetes
medication.
The pharmacist looks surprised and comments,
This is something new. Mrs. Deller has never
been diabetic. Let me see that prescription.
Upon review it is found that the prescription is
actually for Actonel, a medication used for the
prevention and treatment of post-menopausal
osteoporosis, a condition that Mrs. Deller has had
to deal with for a number of years.
The preceding example illustrates how a
combination of problems (illegible handwriting,
failure to read the prescription accurately, failure
to seek clarifcation of the prescription, and lack
of knowledge about the patient) all contributed
to a potentially serious error. It is imperative that
all pharmacy personnel identify and implement
strategies for error reduction and prevention.
The eight rights of medication
administration
Historically, pharmacists, pharmacy technicians,
nurses, and other health care professionals were
taught the fve rights of medication: right
drug, right patient, right dose, right time, and
right route.
12
However, a more current listing of
rights includes three more: right reason, right
response, and right documentation.
2

These broadly stated practices are essential to the
safe and accurate dispensing and administration
of medications.
The right drug
Upon receipt of a prescription or order, it
is imperative that technicians select the
correct medication as prescribed by the
health care provider. If the name of the drug
is unfamiliar, consult a reliable reference.
Unfamiliar names are sometimes the generic
name for a more familiar brand name.
Consult references, if necessary, to identify
the purpose of administering the drug, its
action, routine routes and doses, interactions
with other drugs, herbs, and foods, side
effects, and contraindications. When selecting
the medication, be sure to check the label to
ensure accuracy.
2,12
Pharmacy alert! Never simply grab
medication from a location without checking
the label. Serious errors have been made
when pharmacy personnel automatically go
to the location where a specifc drug has
always been kept. Locations change!
Be alert to changes in color, shape, or size
of pills. If a pill, tablet, or capsule looks
different, it may be the wrong medication!
The right patient
The patients identity should be confrmed
by checking two patient identifers, such as
name, date of birth, address, medical record
number, etc.
2,3
The right dose
Confrm that the dose is appropriate for
the drug, the condition, and the patient.
For example, elderly patients or patients
with compromised renal function may need
reduced doses of some medications. Be sure
to check the drug label with the prescribers
order.
2, 3
The right time
Confrm that the order/prescription is written
for the correct time of day and frequency.
2, 3
The right route
Confrm that the route by which the
medication is to be given is documented on
the prescription and that it is appropriate for
the patient.
2, 3
The right reason
Confrm that the prescribed drug is
appropriate for the patients condition.
The right response
The patients response to the drug must be
monitored. Although the pharmacy staff
may not be present to actually witness
responsiveness, they can and should
communicate with physicians or nurses when
appropriate and include desired response as
part of providing patient education.
2
The right documentation
Documentation and record keeping are
essential. Include documentation of what was
dispensed and any patient education that was
provided.
Elements of a prescription
There are certain elements of a prescription that
must be present to fll and dispense medications.
In all types of settings, the drug, its dose, route,
time and frequency of administration must
be clearly stated without use of unapproved
abbreviations according to accrediting agency
(such as the Joint Commission) standards and
hospital policies and procedures. The prescriber
must sign all orders.
Required elements of a prescription include:
13
Patients full name and address.
Prescribers full name, address, telephone
number, and DEA number.
Date of issuance.
Prescribers signature.
Name of drug, dose, route, quantity.
Directions for use.
Refll instructions.
Whether generic substitution is permissible
(as appropriate to the drug).
Failure to include this information or if the
information is provided but is ambiguous
or illegible, requires clarifcation from the
prescriber.
The Joint Commissions Do Not Use list
In 2002 the Joint Commissions Board of
Commissioners approved a National Patient
Safety Goal requiring accredited organizations
to develop and implement a list of abbreviations
not to be used because of their high potential for
error. It also identifed a list of abbreviations for
possible future inclusion.
7
These abbreviations
are deemed to be dangerous and contribute
to medication errors because they are easy to
misread.
Health care organizations are encouraged to add
to the list as deemed necessary and appropriate.
However, if an organization chooses to add to
the list, policies and procedures must be in place
to support this action, and the organization must
uphold such policies and procedures.
To date the offcial Do Not Use list includes:
7
U or u (unit): Instead, the word unit should
be written.
IU (international unit): The term
international unit should be written.
Q.D., QD, q.d., qd (daily) and Q.O.D.,
QOD, q.o.d., qod (every other day): The
word daily or the phrase every other day
should be written.
Trailing zero (X.0 mg) and lack of leading
zero (.X mg): Decimal points are often
missed. Instead, write X mg or 0.X mg.
MS, MSO4, MgSO4: Morphine sulfate and
magnesium sulfate may be confused for one
another. Instead write out morphine sulfate
and magnesium sulfate.
To date, the following abbreviations and symbols
are being considered for possible future inclusion
in the offcial Do Not Use List. The Joint
Commission recommends that the following
items be considered when as organizations
expand their Do Not Use lists to include an
additional three or more items.7
>; < (greater than and less than symbols):
Write out greater than or less than.
Abbreviations for drug names: Write out
the names of drugs.
Apothecary units: Use metric units.
@: Write at.
cc: Write out mL or ml or milliliters.
ug: write mcg or micrograms.
H.S. (may be taken for at bedtime or half-
strength): Write out half-strength or at
bedtime.
T.I.W.: Write out 3 times weekly or three
times weekly.
S.C. or S.Q.: Write out subcutaneously or
write Sub-Q, or subQ.
Page 56 Elite
D/C (may be taken for discharge or
discontinue): Write out discharge or
discontinue.
A.S., A.D., A.U.: Write out left ear, right
ear, or both ears.
O.S., O.D., O.U.: Write out left eye, right
eye, or both eyes.
Unfortunately, some of these abbreviations
and symbols are still being used. It is up to
the members of the health care team who
are responsible for flling, dispensing, and
administering medications to clarify orders and
not accept orders and prescriptions that contain
abbreviations or symbols that are banned or
ambiguous.
Pharmacy alert! The Institute for Safe
Medication Practices (ISMP) has published a list
of dangerous abbreviations that it recommends
be prohibited. A number of these abbreviations
also appear on the Joint Commissions list.
For further information about the ISMP and its
recommendations, visit the ISMP website at www.
ismp.org.
High-alert medications
High-alert medications are those that involve an
increased risk of causing signifcant patient harm
if administered incorrectly. Although these drugs
may not be linked with an increased number of
medication errors, they are linked to extremely
serious consequences if administered in error.
12
Some common high alert medications include:
14
Insulin.
Anticoagulants, such as heparin and warfarin.
Methotrexate.
Opiates, such as codeine, morphine, fentanyl
and oxycodone.
Electrolytes, such as potassium and sodium,
especially in injectable form.
Chemotherapy agents, such as cisplatin,
hydroxyurea and 5-fuorouracil.
The ISMP maintains a list of high-alert
medications on its website, www.ismp.org. This
list is updated frequently and is created from
information gathered from the ISMP database
on medication errors.
12
It is recommended that
pharmacy technicians visit the ISMP website
(www.ismp.org) regularly for the latest list of
high-alert medications.
By being constantly aware of medications on
this list, procedures can be developed to prevent
errors involving these types of drugs. For
example, when flling orders, special attention
should be paid to automated alerts that pertain
to these medications. The use of additional
labeling on the original medication package can
help to alert pharmacy personnel to high-alert
medications.
12
Look-alike, sound-alike medications
As shown in the scenario at the beginning of this
section, look-alike and sound-alike medications
increase the risk of error. Examples of such
drugs include Celexa and Celebrex, Amaryl and
Reminyl, and Avinza and Evista.
The FDA is working diligently to prevent and
abolish look-alike and sound-alike medications,
but many still exist. Before approving the
name of a new medication, the FDA secures
the services of more than 100 health care
professional volunteers to enact real-life
medication scenarios. The FDA reviews these
scenarios and rejects those names (often as many
as one-third of the proposed names) that look or
sound similar to drugs already approved.
12
The FDA also tracks medication errors caused
by confusion of drug names. If it determines
that a medication name is leading to errors or
near-errors, the FDA can notify health care
providers about the problem and recommend that
the manufacturer change the name of the drug
causing confusion.
12
Both the Joint Commission and the ISMP
have developed lists of medication pairs that
have been involved in medication errors. The
Joint Commission mandates that accredited
facilities identify a list of look-alike/sound-alike
medications to satisfy the safety requirements of
the National Patient Safety Goals.
12
In addition to being especially cautious about
medications that look-alike or sound-alike,
pharmacy personnel must be aware of drugs that
are packaged similarly. Even the same drug in
different strengths can be packaged similarly.
Never use color or style of packaging as a means
of identifying drugs. When working with high-
risk and look-alike/sound-alike medications,
ask a colleague to double-check your work for
accuracy.
3, 4, 12
Dealing with common points of error
3,4,12,14
Prescription drop-off
The point of prescription drop-off is the frst
contact a member of the pharmacy has with a
patient or caregiver and is a great opportunity
for the pharmacy technician to gather as
much information as possible to prevent
potential errors. Strategies for preventing
errors at the point of prescription drop-off
include:
Verify the patients identity by using at
least two identifers. Write the patients
date of birth on every hard copy
prescription even if there are several
prescriptions for the same patient. This
gives the pharmacist easy access to a
second identifer during the fnal accuracy
check of medications. In the hospital
setting, the medical record number can be
used as a second patient identifer.
Check for the existence of new allergies
and medical conditions at every patient
encounter. Both drug and food allergies
should be verifed, because some
medications interact with food allergies
(for example, the fu vaccine should be
avoided in patients with an egg allergy).
New information should immediately
be updated in the patients fle, and
such information should be relayed
to the pharmacist and other pharmacy
personnel as appropriate. Knowledge
of the patients health status helps
identify prescriptions that may be written
incorrectly or for the wrong medication,
and helps the pharmacist verify the
appropriateness of medication therapy.
Good communication with the patient is
very important. Having a conversation
with patients to gather more information
about their current health issue can put
the pharmacy technician in a better
position to catch medication errors.
Order entry
A distraction-free and organized
workplace is extremely important to
the order entry process. Talking with
co-workers, listening to loud music, and
interruptions should be minimized to
decrease the risk of errors when typing
orders into the computer system.
Ensure that there is an ongoing system
of continuing education for pharmacy
personnel. Pharmacy technicians must
continually update their knowledge
of drugs, their actions, doses, routes,
indications, contraindications, and side
effects. They must also remain alert to
newly approved drugs and drugs that
have been recalled or received additional
safety warnings from the Food and Drug
Administration (FDA), and results of
clinical studies on newly developed
drugs.
Pharmacy technicians must be aware
of unacceptable and dangerous
abbreviations and symbols and the
dangers associated with high-alert
medications and look-alike and sound-
alike drugs.
Prescriptions that do not contain
necessary elements, are written illegibly,
or are questionable in terms of safety
must be clarifed before being flled. The
technician should never guess if they are
unsure verifcation with the prescriber
or pharmacist should always be done
if there are any questions about the
prescription.
Never ignore or circumvent technology
safeguards. Drug alerts can be both time
consuming and numerous in numbers.
However, bypassing alerts without
evaluation is unacceptable. Alerts
contain information necessary for the
safe dispensing of medications. Alerts
dealing with drug interactions, allergies,
duplications, and other warnings must be
relayed to the pharmacist.
The technician should be sure to pay
close attention to the placement of
decimal points and zeros on prescriptions.
Misinterpreting a dosage by adding or
missing a zero can result in a potentially
fatal dose, so be sure to double-check
the dosage and alert the pharmacist to
any doses that are uncommon or seem
inaccurate.
Elite Page 57
Filling and dispensing
Many errors during the flling and dispensing
process occur because of inaccurate selection
of product from stock. This is often a result
of medications that are packaged similarly
or have similar names. Safeguards to avoid
errors in the dispensing process include:
Physically separate drugs with similar
packaging and labels.
Ensure that there is a system in place at
the production workstation to guarantee
that the correct product has been
selected. The system may rely on the
National Drug Code checks, barcode
technology, scanned images of products
and prescriptions, or other types of
technology for product verifcation. Also
ensure there are not easy ways to bypass
this system so it can safely prevent errors.
As medications are prepared, labels
should be read carefully, with special
attention given to the NDC number
three times: as the product is chosen, as
the medication is prepared, and when
the stock container is disposed of or
restocked.
Make sure that the computer-generated
prescription label, the stock bottle label,
the hard copy prescription, and the
computer-generated receipt all match.
The pharmacy technician must carry out a
quality review of the prescription before
giving the prescription to the pharmacist
for review.
Accuracy check
An accuracy check must be carried out by the
pharmacist to verify the correctness of:
The information collected when the
prescription was received.
The data entered into the patients fle,
including alerts.
The fnal assembled product.
The pharmacist then evaluates the
prescription to identify any potential
problems that need to be resolved before
dispensing the medication to the patient.
Point of sale
Errors at this point can occur when a
correctly flled prescription is given to the
wrong patient. To avoid this, the person
picking up the prescription should be asked
to provide the patients address, phone
number or birth date. This information
must be compared to the information on the
prescription receipt and product.
Pharmacy alert! Do not ask the patient Is
your address 1012 Main Street? or Is your
birthday May 7? This requires only a yes or
no answer. Ask the patient, Please tell me
your address or What is your birth date?
Other strategies for preventing errors at the
point of sale include:
The names of the medications dispensed
should be reviewed with the patient or
caregiver at the point of sale.
Compare the patients name on the
receipt with the patient name on the
prescription label to ensure the patient
receives both the proper paperwork and
medication.
Implement a process to alert the
pharmacist to the dispensing of high-alert
medications at the point of sale.
Be sure any new prescriptions or those
the patient has questions about are
referred to the pharmacist for patient
counseling.
Be sure that there is a system in place to
alert the technician to reconstitute oral
medications before they are dispensed to
the patient. Oral suspensions should not
be dispensed to the patient unless they
have been mixed with distilled water.
Patient education
Patient education is a very important strategy
in the error prevention process. Research
indicates that more than 50 percent of
potential medication errors can be detected
and prevented during the patient education
process.
3
When a pharmacist is providing patient
education, it is important to explain and
confrm that the patient and caregiver know:
Why the medication is being taken.
How the medication is to be taken.
How the medication works.
When and how to take the medication
(e.g., how often, with or without food,
foods and beverages to avoid while
taking the medication).
The proper dose.
Drug interactions.
Side effects and what to do if they occur.
Pharmacy alert! Do not assume that a
patient with a chronic illness who has been
taking the same drugs for a long time knows
all about his or her medications. Their
knowledge of their medications still needs to
be assessed by the pharmacist!
Considerations for special populations
Because of differences in metabolism and
body size, pediatric and geriatric patients are at
an increased risk of adverse effects and harm
from medication errors. Dosages and dosage
forms should be evaluated with caution in these
patients.
Pediatric patients:
12,15

Calculating medication doses based on
age and weight is especially important for
pediatric patients. If the patients weight
is not included on the prescription, it
should be obtained from the parent or
caregiver at the point of prescription
drop-off. This will allow the technician
to properly calculate the dosage and the
pharmacist to evaluate the accuracy of
the dose.
Parents and caregivers should receive
an oral syringe or device to measure
out liquid medication appropriately to
prevent overdoses.
A separate area of the pharmacy
should be designated for mixing oral
medications to reduce distractions and the
risk of error.
Geriatric patients:
2, 16

Renal and hepatic dysfunction can affect
the clearance and metabolism of drugs,
which may require a reduced dosage in
elderly patients compared to younger
adults. The patients medical conditions
should be assessed at prescription
drop-off in order to determine whether
an elderly patient has kidney or liver
disease.
Elderly patients are also at risk for
medication errors because of multiple
comorbid conditions and polypharmacy.
Maintaining an accurate prescription
record and ensuring that patients
understand what their medications are
used for can help to decrease the potential
for errors.
Considerations for IV medications:
17
All staff involved in the preparation of
IV medications should be thoroughly
trained on aseptic technique and the
compounding of sterile products.
Random assessment of staff and
continuing education are ways to
continue to monitor employees and
prevent errors. Staff members who fail
to pass random assessments should be
retrained to reinforce proper techniques
necessary to minimize errors.
IV medications should always be
prepared in an environment with minimal
distractions. Talking to others or trying
to do multiple tasks at once can increase
the chance of making a serious and
potentially fatal mistake.
All supplies should always be double-
checked as they are laid out for mixing.
Many errors in IV medications result
from the wrong diluent being chosen,
or the wrong drug added to the IV bag.
All supplies used to mix an IV, including
empty vials and syringes drawn to show
the added volume, should be shown to
the pharmacist at the fnal accuracy check
for verifcation.
IVs should always be labeled as they are
made. Leaving IV bags unlabeled for
even a short period of time can result in
mislabeled medications.
Aseptic technique should always be
followed when compounding sterile
products. Introduction of microorganisms
into sterile solutions can have disastrous
consequences for the patient.
Reporting medication errors
Reporting errors is an important strategy for
the prevention of future errors. The purpose
of reporting medication errors is NOT to fnd
someone to blame. Instead, the purpose is to
determine what processes and system failures
exist that contribute to errors and to identify ways
to correct such failures.
Page 58 Elite
The U.S. Pharmacopeial Convention (USP)
operates three medication error-reporting
systems:
12
Medication Errors Reporting (MER)
program.
The Veterinary Practitioners Reporting
program.
MEDMARX.
The MER program operates in conjunction
with ISMP. Health care professionals can report
medication errors anonymously online, by
phone (1-800-23-ERROR), or by mailing or
faxing a report to USP. The USP reviews the
information and forwards fndings to the FDA
and manufacturers.
12
MEDMARX is a system to which health care
centers can subscribe to document internal
information on medication errors and adverse
reactions.
12
All errors should always be reported as soon
as possible after the error occurred, and should
include information about how and why the
error happened and how similar errors will be
prevented in the future.
Patients should be informed of the error within
24 hours of the event being discovered. They
should receive an apology and be informed about
what impact the error may have. Patients should
also be told of the actions being taken to prevent
errors in the future.
12
Patient safety and responsibility
All error prevention strategies are grounded in the
desire to ensure patient safety. However, it is also
important to think about the responsibility that
patients and caregivers have for their own safety
and well-being. If medications are correctly
prepared and dispensed and patient education
provided (including adequate evaluation of
the patients knowledge), patients and their
caregivers are responsible for:
Taking medications as prescribed.
Recognizing and reporting side effects as
instructed.
Pharmacy alert! It is especially important
that patients and caregivers be taught what
side effects require immediate emergency
medical intervention, such as diffculty
breathing and swelling of the lips and tongue,
which indicate anaphylactic reaction. They
also need to be taught how to obtain help
(e.g. dial 911) in emergencies.
Keeping health care providers and pharmacy
staff informed about changes in their health
status.
Recognizing that their medications are
different from what they usually take (e.g.
appearance, size, color, etc.) and reporting or
questioning these differences before taking
these medications.
Actively participating in planning their own
treatment regimen.
Maintaining a current, accurate list of all
medications they take and informing health
care providers and pharmacy staff about this
list and any changes if they occur.
Pharmacy alert! Patients must be taught to
include ALL medications on their list and to
inform health care providers and pharmacy
staff as well. Some patients do not think to
include over-the-counter (OTC) medications
or herbs or vitamins on their list of
medications. Some think that because herbs
are natural, they have no adverse effects.
Patients must be taught that prescribed
drugs, OTC medications, herbs, vitamins,
minerals, and other supplements all have the
potential to cause adverse effects and some
harmful interactions.
Some patients may not be accustomed to being
treated as part of the health care team. They just
assume that health care professionals know best,
and they do not ask questions even though they
may have some concerns. The Joint Commission
has developed some helpful patient education
materials that help to teach patients to take
responsibility for their own health status, to ask
questions, and to report concerns.
The series is called Speak Up, and addresses
such issues as asking about medications, stroke,
infection control, and reducing the risk of falls.
Much of the patient education material related
to the Speak Up series is free and available in
English and Spanish on the Joint Commissions
website at www.jointcommission.org.
Root-cause analysis
Understanding why a medication error occurred,
the factors that contributed to its occurrence, and
the systems that failed to work to prevent the
error are essential to learning from mistakes and
identifying actions to take to avoid future errors.
Root-cause analysis is a process for analyzing
errors that goes beyond identifying individuals
who were involved in the adverse occurrence. It
is an organized investigation conducted for the
purpose of fnding out why an error occurred and
what can be done to prevent errors in the future.
8, 9
The root-cause analysis should be performed
by an interdisciplinary team whenever possible.
This may be more easily done in a hospital or
outpatient health care center setting where many
disciplines work together and risk management
personnel are on-site to participate in or lead the
team analysis. In cases such as these, the actual
person or persons involved in the error should not
be part of the initial analysis. They will provide
information and be included in reviewing the
data analysis and helping to write action plans
for systems improvement. But it may be diffcult
for them to participate in an objective analysis
throughout the entire process, especially if the
error led to serious patient harm. Most facilities
have policies and procedures to govern the root-
cause analysis process, including team members
and determining outcomes.
In smaller facilities, such as small outpatient
pharmacies, the team may be limited to pharmacy
staff and physicians. In some cases, patients
or caregivers may be part of the root-cause
analysis team, especially if the patient or
caregiver failed to follow instructions or carry
out recommendations provided during patient
education. The ultimate goal is to conduct an
analysis that will lead to actions that will improve
patient safety.
There are a number of ways to conduct a root-
cause analysis. Various forms and checklists are
used to organize the investigation, document
data, and write out action plans. The goal of the
root-cause analysis is to retrospectively determine
how and why an error occurred and identify what
actions need to be taken to improve safety and
reduce errors.
After implementing identifed safety precautions,
the team must also review the effectiveness of
these actions. If actions fail to have the desired
effect on safety and error reduction, the analysis
must be reviewed and new actions identifed.
All errors must be analyzed, but a complete root-
cause analysis may not be necessary for every
error. For example, in a hospital setting, a patient
was given one dose of 500 mg of an antibiotic
when 250 mg was ordered and no harm came to
the patient. A brief analysis may be conducted
to identify contributing factors and correct
processes.
However, any event of a serious nature that
caused signifcant harm or had the potential to
cause signifcant harm should be analyzed via the
root-cause analysis process. All sentinel events
must have a root-cause analysis.
The Joint Commission offers A Framework
for A Root Cause Analysis and Action Plan in
Response to a Sentinel Effect that summarizes
the steps to be taken in a root-cause analysis
and can be accessed on the Joint Commission
website.
8
The suggestions that follow are based
on this framework.
Each category is accompanied by questions or
suggestions for information to be obtained that
must be addressed as part of the analysis. Note
that not all questions will apply in every event,
and others may need to be addressed.
What happened?
Was this event a sentinel event?
What type of harm resulted from the
adverse event?
Provide a brief description of the event,
including the date, day of the week, and
time of day that the event occurred.
What areas of the facility were involved?
(pharmacy, nursing unit, outpatient clinic,
etc.)
Why did it happen?
What was the process or activity during
which the event occurred?
What are the steps in this process or
activity?
A fow chart or diagram may be useful to
help see the fow of events.
What were the contributing factors?
What factors contributed to the event?
What human factors contributed to the
event?
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Did equipment performance play a part
in the event or affect the outcome of the
event?
What environmental factors contributed
to the event?
What uncontrollable external factors
contributed to the event? (These must
truly be uncontrollable. For example, a
disaster such as a tornado is not directly
controllable).
Are there any other factors or issues that
had an impact on the outcome?
What other services were impacted by
this event?
Why did the event occur? What systems
and processes contributed to the event?
What human resource issues contributed
to the event?
Were involved staff members adequately
qualifed and currently competent for the
responsibilities they were expected to
carry out?
Did staff members receive adequate
orientation, in-service training, and
ongoing continuing education and
training for their roles and responsibilities
in the events surrounding the event? Is
the process of planning and delivering
such education adequate?
How did staffng compare to
recommended or mandated levels? Were
there inconsistencies in staffng levels as
required by facility policy and procedure
and other mandates?
What were the plans for dealing with
issues that reduce effective and adequate
staffng levels? Were these plans carried
out if staffng was not adequate? Why or
why not?
To what extent is staff performance
addressed as part of the event?
What information management issues had
an impact on the event?
Was necessary information available
(e.g., reference materials, supervisory
assistance, medical input) when needed?
Was such information accurate, complete,
and clear? Why or why not?
Was communication among involved
participants adequate? Why or why not?
What environmental issues had an impact
on the event?
Was the physical environment
appropriate for the processes that had to
be carried out? Why or why not?
What systems and processes are in place
to identify environmental risks?
What types of emergency and failure-
mode responses have been identifed,
planned, and tested?
What leadership issues had an impact on
the event?
To what extent is the culture of the
facility favorable to identifcation of risk
and reduction of risk?
What barriers to communication exist
that have the potential to increase risk of
errors?
To what extent is the prevention of
adverse outcomes communicated
throughout the facility as a high priority?
How is this addressed? Are all staff
members aware of this as a priority?
What can be done to protect patients
and staff members against the effects of
uncontrollable factors? Have such actions
been identifed? Are plans in place to
address these factors? Why or why
not? What are the plans? How are their
effectiveness assessed?
After gathering and analyzing the data from the
preceding questions, an action plan to reduce risk
must be developed. Each item of the action plan
must be clearly stated in measureable terms. For
example, an action item might state Implement
a double-check of all high-alert drugs by having
two pharmacists review and document the
accuracy of flling a high-alert prescription before
it is dispensed. This is concise and measureable.
It would not be appropriate to state, Understand
that high-alert medications must be double-
checked. This does not clearly state what is to be
done or how it is to be done.
Each action item should identify a person or
persons responsible for implementing the action,
including writing out a new procedure or policy
as needed. A date for implementation of the
action item should also be identifed.
The root-cause analysis team should also set
a date to evaluate the effectiveness of the
action items. They must determine whether the
actions they have identifed are effective and
help to reduce error. If actions are found to be
ineffective, new actions must be identifed and
consequently evaluated for effectiveness.
Part of the action plan for adverse events, no
matter how minor, should be to counsel the
persons involved. The pharmacist, the pharmacy
technician, the physician, and the nurse who
are involved in an error (especially an error
that causes signifcant patient harm) may suffer
from fear, guilt, and lowered self-esteem. They
may also suffer from physical effects such as
insomnia, physical or emotional illness, and
diffculty resuming their work responsibilities.
It is important to provide support for these
individuals as well as to instruct them on ways to
reduce errors in the future. And it is imperative to
note that error analysis should not be conducted
as a way to fnd someone to blame. It is
a process to help improve job performance,
enhance patient safety, and improve the quality
and appropriateness of the patient environment.
Education interventions that can help
reduce medication errors
Ongoing education is necessary if health care
professionals are to reduce the occurrence of
medication errors. But what should be part of
ongoing education? Ongoing education should
go beyond basics and include statistical
information about medication error occurrences
within a facility and on a national basis, how to
access national resources on medication errors,
and facility-based strategies to safeguard patient
safety.
Orientation
Orientation of new employees is the
starting point for education. An overview of
facility policies and procedures on the safe
preparation and dispensing of medications
as well as a review of the eight rights of
medication is appropriate. New employees
should also be told about the current state
of medication safety within the facility in
which they work and what plans are in place
to further enhance such safety. Orientation
should be competency-based, and new
employees must demonstrate competency
in their basic job responsibilities as part of
orientation.
In-service or on-the-job training
This type of education refers to education
that must be offered quickly because of
an immediate need. An example of such
education occurs when a new or unusual
medication is ordered. Before it can be
prepared and dispensed, it is necessary to
discuss what the medication is used for, its
action, route of administration, range of
dosage, side effects, and interactions.
It is also necessary to provide the entire
pharmacy staff with in-service training.
Never assume that it is suffcient for one or
two employees to be trained; all personnel
who are involved in the topic being discussed
should be in attendance at in-service training.
Other members of the health care team (e.g.,
nurses, therapists, etc.) should also be part of
the in-service training, if appropriate.
Continuing education
Continuing education refers to education
that is offered to enhance the skills of health
care professionals beyond the basics.
Continuing education is designed to increase
knowledge, skill, and professional growth
on an ongoing basis. It allows pharmacy
personnel to take responsibility for their own
professional growth and development and for
improving patient safety, especially when it
comes to medication errors.
Continuing education can take many formats.
It may involve attending conferences or
all-day programs offered at locations other
than the facility for which one works. It can
be a program that is presented before the
beginning of the work day or after normal
working hours. It can also be presented on
demand via computer, iPhones, iPads, etc.
Journal clubs are another useful way to present
continuing education. Keeping up with the latest
information, which comes from a variety of
sources such as journals and the Institute of Safe
Medication Practices, is diffcult. Staff members
could be assigned to present information from
a particular resource during staff meetings on a
Page 60 Elite
regular basis. This would allow all personnel to
receive educational information without having
to read every journal or consult every resource
themselves. This approach also encourages all
staff members to assume responsibility for their
own ongoing continuing education.
Another facet of continuing education is honest
information about medication safety in the
workplace. Data from risk management, quality
improvement, and research projects should
be presented. All employees have the right
to know what works and what does not work
when it comes to medication safety. Employees
should learn about national statistics as well as
the statistics at their own facilities. Such data
should be shared with all employees so they can
learn the current status of medication safety in
their workplace and have input into improving
medication safety.
Part of the continuing education process can
involve teaching staff members to participate on
committees and task forces on medication safety.
Those staff members who prepare, dispense, and
interact with patients are the persons who can
provide the most practical input when it comes
to designing systems and writing policies and
procedures to enhance medication safety.
The effectiveness of all types of education should
be assessed. For example, after a program on
adverse drug interactions, did the occurrence
of such problems decrease? Did staff members
ability to recognize potential dangerous
interactions increase? It is not enough to offer
education. There must be a process in place to
determine whether the education was effective
in terms of an increase in knowledge and patient
safety.
Certifcation of pharmacy technicians may
also prove to be a strategy for medication error
reduction and prevention. Results from a 2010
survey sponsored by the Pharmacy Technician
Certifcation Board showed that more than 80
percent of the 3,250 pharmacists surveyed agreed
that pharmacy technician certifcation is linked
to a reduction in medication errors. Eighty-three
per cent of respondents noted that working with
technicians who were certifed increased the
amount of time pharmacists were able to spend
on patient care.
4

It comes as no surprise that well-trained and
educated pharmacy technicians are expected to
have a positive impact on patient care and safety.
In fact, there is an anticipated 25 percent increase
in the number of pharmacy technician positions
by the year 2018.
4
Conclusion
In summary, the reduction of medication errors
involves many factors. The most important factor,
however, is the ability of all pharmacy personnel
to assume responsibility for a safe patient
environment and to actively pursue strategies
that will both improve such safety and enhance
professional growth and development.
References
1. Bohand, X., et al. (2008). Frequency, types, and potential clinical signifcance of
medication-dispensing errors. Retrieved January 22, 2012 from www.ncbi.nlm.nih.gov/
pmc/articles/PMC2671971/
2. Comeford, K. C. (Ed.). (2012). Nursing 2012 drug handbook. Philadelphia: Wolters
Kluwer Health/Lippincott Williams & Wilkins.
3. Drug Store News. (2009). The technicians role in medication error reduction
strategies. www.cedrugstorenews.com, spring, 2009, 18-22.
4. Drug Store News. (2010). PTCB survey: Pharmacists think pharmacy technicians can
reduce medication errors. Retrieved January 22, 2012 from www.drugstorenews.com/
article/ptcb-survey-pharmacists-think-pharmacy-technicians-can-reduce-medication-
errors.
5. Gaunt, M. J. (2010). Apharmacy technicians role in medication error prevention.
Retrieved January 22, 2012 from http://www.pharmacytimes.com/publications/
issue/2010/January2010/MedicationSafety-0110/ zz6.
6. Goeking, M. (2011). What is the role of a pharmacy technician? Retrieved January 22,
2012 from www.pharmacytechpros.com/role-of-a-pharmacy-technician.html.
7. The Joint Commission. (2004-2011). Facts about the offcial Do Not Use list.
Retrieved January 22, 2012 from www.jointcommission.org.
8. The Joint Commission. (2009). Aframework for a root cause analysis and action
plan in response to a sentinel event. Retrieved January 22, 2012 from http://www.
jointcommission.org/Framework_for_Conducting_a_Root_Cause_Analysis_and_
Action_Plan/
9. Knudsen, P., Herborg, H., Mortensen, A. R., Knudsen, M., & Hellebek, A. (2007).
Preventing medication errors in community pharmacy: root-cause analysis of
transcription errors. Quality and Safety in Health Care, 16(4), 285-290.
10. McClinton, R. S., & Meinking, R. (2011). Reducing pharmacy technician hospital
errors. U.S. Pharmacist, 36(12), 22-28.
11. National Coordinating Council for Medication Error Reporting and Prevention.
What is a medication error? Retrieved January 31, 2012 from www.nccmerp.org/
aboutMedErrors.html.
12. Schlesselman, L. S. (2008). 10 strategies to reduce medication errors. Retrieved
January 22, 2012 from https://secure.pharmacytimes.com/lessons/200809-01.asp.
13. University of Kansas Medical Center (retrieved 2012). Components of written
prescriptions. Retrieved March 5, 2012 from http://www2.kumc.edu/instruction/
prescriptStuff/format.htm
14. Preventing Med Errors. Pharmacy Technicians Letter. September 2012. Accessed
June 22, 2013 at http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?ni
dchk=1&cs=RITEAID&s=PL&dd=250730&cat=5569&pt=2
15. Levine SR, for the Institute for Safe Medication Practices and the Pediatric Pharmacy
Advocacy Group. Guidelines for preventing medication errors in pediatrics. Journal of
Pediatric Pharmacology and Therapeutics. 2001:6;42642. Accessed June 22, 2013 at
http://ppag.org/images/pdf/Guidelines_Peds.pdf.
16. Fialova D, Onder G. Medication errors in elderly people: Contributing factors and
future perspectives. Br J Clin Pharmacol. 2009;67:6415. Accessed June 22, 2013 at
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723202/
17. Cousins DH, Sabatier B, Begue D, et al. Medication errors in intravenous drug
preparation and administration: a multicentre audit in the UK, Germany and France.
Qual Saf Health Care 2005 14: 190-195. Accessed June 22, 2013 at http://qualitysafety.
bmj.com/content/14/3/190.full.pdf+html.
THE PHARMACY TECHNICIANS ROLE
IN REDUCING MEDICATION ERRORS
www.elitecme.com.
26. Preventing errors at which of the following
common points of error is not the
responsibility of the pharmacy technician?
a. Prescription drop-off.
b. Point of sale.
c. Filling and dispensing.
d. None of the above.
27. Which of the following pieces of
information can be used as a second patient
identifer at the point of sale?
a. Birthdate.
b. Address.
c. Phone number.
28. Which of the following groups of patients
are at a higher risk of dosage errors because
of decreased renal or hepatic dysfunction?
a. Pediatric patients.
b. Geriatric patients.
c. Deaf patients.
d. Adolescent patients.
29. If a medication error occurs, when should it
be reported?
a. Within one week.
b. Within one month.
c. As soon as possible after the error
occurs.
d. Whenever it is convenient to report.
30. Which of the following types of education
should be used to minimize errors in the
pharmacy environment?
a. Continuing education.
b. In-services or on-the-job training.
c. Orientation.
RPTAZ02MEE13
Elite Page 61
NOTES
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