What is the meaning of

pharmacokinetics?
The sutyd of drug movement
throughout the body. lt describes
how the body deals with
medications.
What is the greates barrier
drugs face in reaching their
target cells?
Crossing membranes
What are the four categories of
pharmacokinetics (processes)?
1. absorption
2. distribution
3. metabolism
4. excretion
What 2 ways do drugs cross
body membranes?
1. Active transport (against
concentration/electrochemical
gradient)
2. Diffusion/passive transport
What is absorption?
A process involving the movement of a
substance from its site of administration,
across body membranes, to circulating
fluids.
Which is faster in regard to
absorption--lM
administration or lV
administration? Why?
lV administration because it
enters the bloodstream
directly.
What factors affect
aborption?
Dose of medication
Speed of digestion
Exposure to enzymes (Gl)
Blood flow to site of admin.
Degree of ionization (pH)
Drug/Drug and Food/Drug interactions
ln a basic environment,
aspirin is mostly in what
form? What happens to the
absorption?
lonized form
ln this case, absorption is
prevented.
ls aspirin an acidic or a
basic substance?
Aspirin (ASA) is a weak acid
What is affinity in regard to
pharmacokinetics?
Affinity is the attraction that tissues
have for certain medications.
Only (bound/unbound) drugs can
reach their targe cells or be
excreted by the kidneys.
Unbound (free) drugs
Give examples of two spcial
anatomic barriers that prevent
many chemicals and medications
from entering.
Blood-brain barrier
Fetal-plancental barriers
List some medications that are
readily able to cross the blood-
brain barrier and produce actions
in the CNS.
sedatives
anti-anxiety agents
anticonvulsants
List some substances that easily
cross the plancental barrier and
can potentially harm the fetus.
alcohol
cocain
caffeine
certain Rx meds
What is another name for
metabolism in regard to
medications?
biotransformation
What is the hepatic
microsomal enzyme
system?
The enzyme complex (P-450
system) which inactivates drugs
and acclerates their excretion.
What is the "first-pass"
effect?
This is when drugs absorbed after oral administration
cross directly into the hepatic portal circulation, which
carries blood to the liver before it is distributed to other
body tissues (therefore, some drugs can be completely
metabolized to an inactive form before reaching the
general circulation)
List the steps of the first-
pass effect
1. drugs are abbsorbed
2. drugs enter the hepatic portal circultion and go driectly
to the liver forming...
3. drug conjugates, leaving liver
4. drug is distributed in the general circulation
What are conjugates?
Side chains added to drugs during
metabolism to make them more water
soluble and easily excreted by the
kidneys.
What are prodrugs?
Agents that have no pharmacologic activity
unless first metabolized to their active form by
the body
ie: benazepril (Lorensin)
losartan (Cozaar)
What is enzyme induction?
The process that increases metabolic activity in the liver,
which may require higher doses of meds to achieve the
optimum therapeutic effect.
(ie: phenobarbital causes the liver to synthesize more
microsomal enzymes, therefore increases the rate of its
own metabolism.)
What is excretion?
Drugs being removed from
the body.
What is the primary site of
excretion?
Kidneys
What is the kidney filtration
rate in an average-size
person?
180 L of blood each day
What substances are
filtered at the glomerulus?
Free drugs
Water-soluble agents
Electrolytes
Small molecules
What substances are not
filtered due to large size?
Proteins
Blood cells
Conjugates
Drug-protein complexes
Patients with renal failure will have
(diminished/enhanced) ability to
excrete medications
Diminished, therefore they
may retain drugs for an
extended period of time.
The rate of respiratory excretion is
dependent on factors that affect
gas exchange. List those factors.
Diffusion
Gas solubility
Pulmonary blood flow
What is the relationship between
breathing rate/blood flow to lungs
and excretion?
The faster the breathing rate, the
greater the excretion;
The greater the blood flow into
lung capillaries, the greater the
excretion.
Where are water-soluble
drugs secreted?
Saliva
Sweat
Breast milk
Explain why some patients
experience an "odd" taste when
given lV drugs
This is attributed to the
secretion of agents into the
saliva
Why should nursing mothers
always check with their provider
before taking any Rx, OTC drugs,
or herbal supplements?
Because these agents can be
secreted into breast milk, thus
becoming an exposure risk to the
infant.
What is the minimum
effective concentration?
The amount of drug
required to produce a
therapeutic effect
What is the toxic
concentration?
The level of drug that will
result in serious adverse
effects
The plasma concentration between the
minimum effective concentration and the
toxic concentration is called the what?
Therapeutic range
Define plasma half-life
The length of time required for the
plasma concentration of a medication to
decrease by one-half after administration
(can be a few minutes to hours or days)
What is the relationship
between half-life and
excretion?
The greater the half-life, the longer it takes a
medication to be excreted.
ie: A drug with t 1/2 of 10 hours would take
longer to be excreted than a drug with t 1/2 of 5
hours.
Given the following:
t 1/2 = 14 hours
t 1/2 = 2 days
Which medication would produce
an effect that would last longer in
the body?
The drug with the t 1/2 of 2 days
(longer half-life = longer duration,
longer effect, takes longer to be
excreted)
Drugs with relatively short half-lifes (ie:
aspirin t 1/2 =15-20 min) need to be
given how often? What about drugs with
longer half-lifes (ie: Plendil t 1/2 = 10
hours)?
Aspirin--every 3-4 hours
felodipine
(Plendil)==once/day
lf a patient has extensie renal or hepatic
disease, the plasma half-life of a drug will
(increase/decrease). Explain.
lncrease. The drug concentration
may reach toxic levels, therefore
dosages must be reduced and
meds given less frequently.
How long does it take
(theoretically) to reach even
distribution of continuous
therapeutic level of drug to body
tissues (equilibrium)?
4 half-lives
What is a loading dose?
Maintenance dose?
Loading--higher amount of drug, often given
only once or twice to "prime" the bloodstream
with a sufficient level of drug
Maintenance--given to keep the plasma drug
concentration in the therapeutic range.
Using a routing dosing
schedule with antibiotics,
how long does it take to
reach therapeutic level?
Almost 5 doses (48 hours)
How long does it take to reach
therapeutic level when using a
loading dose of antibiotics?
Level is reached within 12
hours
What can frequency
distribution curves show?
1. The number of patients responding to
a drug action at different doses
2. Represents the safety of a drug (think
median lethal dose)
Give the equation for
Therapeutic lndex
Tl = median lethal dose
divided by median effective
dose
What is the meaning of
therapeutic index?
lt is a measure of the drug's safety
margin: The higher the
therapeutic index, the safer the
medication
How is the median toxicity
dose calculated?
TD50 is the dose that will produce
a given toxicity in 50% of a group
of patients.
How is median lethal dose
calculated?
The LD50 cannot be
experimentally determined in
humans, so it is tested on animals
during the phase trials.
What is the relationship between
the two components of the
equation for therapeutic index?
The larger the difference between
the two doses, the greater the
therapeutic index, thus the safer
the medicine.
Explain potency
A drug that is more potent will
produce a therapeutic effect at a
lower dose, compared with
another drug in the same class.
Explain efficacy
The magnitude of maximal
response that can be produced
from a particular drug.
Which is more important?
Potency or efficacy?
Efficacy is almost always more
important than potency, from a
pharmacotherapeutic perspective.
How do drugs act?
By modulating or changing
existing physiologic and
biochemical processes.
What is a receptor?
The cellular macromolecule to
which a medication binds in order
to initiate its effects
Explain the receptor theory
A drug binds to a receptor to cause a change in body
chemistry or physiology. These receptors do not exist in
the body solely to bind drugs. Their normal function is to
bind endogenous molecules (hormones,
nerotransmitters, growth factors)
What type of substance are
the majority of
macromolecules?
Proteins
Once a drug binds to the
receptor, what happens?
A series of second messenger events within the cell may
be triggered (ie: conversion of adenosine
triphosphate--ATP--to cyclic-AMP) and biochemcial
cascades initiate the drug's action by either stimulating
or inhibiting normal activity of the cell.
How many basic receptor
types exist?
Two--alpha and beta
Both have subtypes (alpha 1&2,
and beta 1&2)
A drug that produces the same
type of response as the
endogenous substance is known
as
an agonist
What is an antagonist?
A drug that occupies a receptor
and prevents the endogenous
chemical from acting.
ls atropine an agonist or an
antagonist?
An antagonist--it inhibits the
effects of acetylcholine by
competing for the binding sites
ls competitive inhibition the
only way antagonists work?
Explain.
No. Functional antagonists inhibit the effects of
an agonist not by competing for a receptor but
by changing the pharmacokinetic factors
(slowing absorption, speeding up metabolism or
excretion, etc.)
Males of Mediterranean and
African descent are more likely to
express a deficiency in the
enzyme glucose-6phosphate
dehydrogenase (G6PD). What
does this result in?
ln administering certain drugs (ie: primaquine,
sulfonamides, nitrofurantoin) an acute hemolysis of red
blood cells occurs and up to 50% of the circulating RBCs
may be destroyed. Nurses must observe patients
carefully following the admin of these meds. Their are
alternative medications.
What are idiosyncratic
reactions?
Unpredictable and
unexplained drug reactions
What is a drug that occupies a
receptor site and prevents
endogenous chemicals from
acting?
An antagonist
Morphine has a greater efficacy than either of the OTC
drugs aspirin or acetaminophen. Based on what a nurse
knows about efficacy, what patient condition might
require a dose of morphine rather than aspirin or
acetaminophen?
A patient in moderate to
severe pain after the otehr
drugs have been ineffective
for pain relief
You read that the drug to be given
to a patient has a "narrow
therapeutic index", this means
The drug has a narrow safety
margin and even a small increase
in dose may produce adverse or
toxic effects.