Definition:

Drug addiction, also known as Substance Dependence, is a chronically relapsing

disorder that is characterized by (1) compulsion to seek and take the drug, (2) loss
of control in limiting intake, (3) emergence of a native emotional state (e.g.
dysphoria, anxiety, irritability) when access to the drug is prevented.
- By WHO (1964), a state of periodic or chronic intoxication detrimental to the
individual and society, which is characterized by an overwhelming desire to
continue taking the drug and to obtain it by any means.
Drug is a substance used as a medicine in the treatment of diagnosed mental or
physical illness; any chemical substance, other than food, that affects the structure
of a living thing.
Addiction
- from the Latin verb addicere > to give or bind a person to one thing.
- Generally, used in the drug field to refer to chronic, compulsive or
uncontrollable drug use, to the extent that a person (referred to as an
addict) cannot or will not stop the use of some drugs.
- It usually implies a strong (Psychological) Dependence and (Physical)
Dependence resulting in a Withdrawal Syndrome when use of the drug is
stopped.
Drug addiction has been conceptualized as a disorder that progresses from
impulsivity to compulsivity in a collapsed cycle of addiction comprised of three
stages:
1. Preoccupation/ Anticipation
2. Binge/ Intoxification
3. Withdrawal/ Negative Effect
Drug abuse are divided into 4 Major categories:
1. Depressants (opioids, benzodiazepines, alcohol)
2. Stimulants (cocaine and the amphetamines)
3. Hallucinogens (Lysergic Acid Diethylamide [LSD] & Phencyclidine [PCP])
4. Miscellaneous (Marijuana and Nicotine)
Heroin (Diacetylmorphine)
- Synthetically derived from the natural Opioid morphine
- Rapid on set of action and very short half-life
- Classified in Schedule I
- Prodrug (which is not itself active)
- Most effective when used intravenously
- Used intranasally, sometimes smoked in the free base form, both to reduce
the risk of human immunodeficiency virus (HIV I) transmission from
intravenous use and because of the wider availability of high-purity heroin in
recent years.
- Rapidly deacetylated to 6-mono-acetylmorphine and morphine, both of which
are active at the mu opioid receptor
Morphine
- Is a natural product of the seeds of the Poppy plant, Papaver somniferum.

An alkaloid that belongs to the class of Phenanthrenes (also includes codeine

and thebaine)
- Prescribed primarily as a high-potency analgesic
- Synthetic Compounds :
a. Oxycodone (OxyContin)
Combined with aspirin and acetaminophen for moderate pain; available
orally without co-analgesic for severe pain
Semi-synthetic compound derived from thebaine, with agonist activity,
primarily at mu receptors.
Has 1:2 equivalence to morphine
b. Codeine
Is methylmorphine, with methyl substitution on the phenolic hydroxyl
group of morphine
More lipophilic than morphine and thus crosses the blood-brain barrier
faster
Less first-pass effect metabolism in the liver = greater oral bioavailability
than morphine
Less potent than morphine
c. Meperidine
A phenylpiperidine with a number of congeners
Mostly affective in the CNS and bowel
No longer used for treatment of chronic pain
d. Pentazocine
Is one of the initial agonist-anntagonist medications, a weak antagonist
or partial agonist at the mu receptor and is also a kappa receptor partial
agonist.
e. Hydromorphone
Is a more potent opioid analgesic than morphine
Used for the treatment of moderate to severe pain and is excreted along
with its metabolites by the kidney
Can be given IV, infusion, orally, and per rectum, with low oral
bioavailability
f. Hydrocodone
Prescribed for relatively minor (such as dental) pain
Used in combination with acetaminophen; thus there can be
hepatotoxicity associated with its abuse.
g. Methadone
Synthetic long-acting full mu-opioid agonist given orally
h. Levo-alpha-acetylmethadol
Is a synthetic, longer-acting (48 hour) congener of methadone that also is
orally effective
i. Buprenorphine
Alone and in combination with naloxone (as an office-based sublingual
treatment for heroin and opioid addiction
Heroin and Morphine difference
- Heroin has a more rapid onset of action but is converted rapidly to morphine
to the body
- Heroin is up to 5 times more potent than morphine

Greater capacity of morphine to produce the sensation of pins and needles

and itching
The mechanism of development of tolerance and physical dependence is not
related to pharmacokinetic factors but is a true cellular adaptive response
that is associated with changes in second messenger systems related to Ca
+2 flux, adenylyl cyclase inhibition, or G protein synthesis. Chronic exposure
and tolerance to opioids is associated with an elevation of intracellular Ca+2
content- unlike acute exposure, which often causes a decrease. The effect
appears to be related to a change in the receptors ability to associate with G
coupling protein, increase level of G proteins, and an up-regulated cAMP
system. In addition, the number of receptors may be reduced by
internalization and by reduced synthesis.
Opioid Antagonist: act at specific receptor sites, their effects can be blocked
by other drugs which can occupy those receptors. Naloxone is such an
antagonist, and it represents perhaps the only true antidote in medicine.
Persons suffering from an acute overdose of opioids will be immediately
awakened by intravenous naloxone because it competes successfully with
opioid molecules at receptor sites.

Cocaine
- Is an alkaloid with a tropane ester chemical structure similar to that of
scopolamine and other plant alkaloids.
- Occurs in leaves of coca bush, Erythroxylon coca
- Local anesthetic > to dilate pupils
- Treatment for depression and alcohol dependence (Sigmund Freud), but
addiction quickly brought an end to this idea.
- Cocaine hydrochloride is a water-soluble salt that can be injected or absorbed
by any mucosal membrane (eg. Nasal snorting). When heated in an alkaline
solution, it is transformed into the free base, crack cocaine, which can then
be smoked. Inhaled crack cocaine is rapidly absorbed in the lungs and
penetrated swiftly into the brain, producing an almost instantaneous rush.
- In the peripheral nervous system, cocaine inhibits voltage-gate sodium
channels, thus blocking initiation and conduction of action potentials.
- In the central nervous system, cocaine blocks the uptake of dopamine,
noradrenaline, and serotonin through their respective transporters. The block
of the dopamine transporter (DAT), by increasing dopamine concentrations in
the nucleus accumbens, has been implicated in the rewarding effects of
cocaine.
- The activation of the sympathetic nervous system results mainly from
blockage of the norepinephrine transporter (NET) and leads to an acute
increase in arterial pressure, tachycardia, and often, ventricular arrhythmias.
Users typically lose their appetite, are hyperactive and sleep little.
- Cocaine exposure increases the risk of intracranial hemorrhage, ischemic
stroke, myocardial infarction, and seizures. Cocaine overdose may lead to
hyperthermia, coma, and death.
- Susceptible individuals may become dependent and addicted after only a few
exposures to cocaine. Although a withdrawal syndrome is reported, it is not
as strong as that observed with opioids. Tolerance may develop, but in some
users a reverse tolerance is observed; that is, they become sensitized to

small doses of cocaine. This behavioral sensitization is in part contextdependent.

Cravings are very strong and underline the very high addiction liability of
cocaine.

Marijuana
dry, shredded green or brown mixture of leaves, stems, seeds, and leaves of
the hemp plant Cannabis sativa.
- The dried mixture can be smoked like a cigarette or in a pipe or in a cigar
where the tobacco has been removed from the inside.
- Endogenous cannabinoids that act as neurotransmitters include 2-arachidnoyl
glycerol (2-AG) and anandamide, both which to CB1 receptors. These very
lipid-soluble compounds are released at the postsynaptic somatodendritic
membrane, and diffuse through the extracellular space to bind at presynaptic
CB1 receptors, where they inhibit the release of either glutamate or GABA.
Because of such backward signaling, endocannabinoids are called retrograde
messengers. In the hippocampus, release of endocannabinoids from
pyramidal neurons selectively affects inhibitory transmission and may
contribute to the induction of synaptic pasticity during learning and memory
formation
- Active substances include 9-tetrahydrocannabinol (THC), a powerful
psychoactive substance
- Like opioids, THC causes disinhibition of dopamine neurons, mainly by
presynaptic inhibition of GABA neurons in the VTA. The half-life of THC is
about 4 hours. The onset of effects of THC after smoking marijuana occurs
within minutes and reaches a maximum after 1-2 hours.
- The most prominent effects are euphoria and relaxation, also feelings of wellbeing, grandiosity, and altered perception of passage time
- Dose dependent perceptual changes (eg, visual distortions), drowsiness,
diminished coordination, and memory impairment may occur
- Additional effects of THC (increased appetite, attenuation of nausea,
decreased intraocular pressure, and relief of chronic pain)
- Chronic exposure to marijuana leads to dependence, which is revealed by a
distinctive, but mild, and short-lived, withdrawal syndrome that includes
restlessness, irritability, mild agitation, insomnia, nausea, and cramping.
Methamphetamine
Behavioral mechanism of action
- Amphetamine abusers
persists in repetitive thoughts or acts for hours = Punding - organized,
goal-directed, but meaningless activity.
eg. repetitively cleaning the home or an item such as a car, bathing in a
tub all day, elaborately sorting out objects or endlessly dismantling or
putting back together items such as clock or radios
MOA
- Cocaine and Methamphetamine block neuroronal nicotinic acetylcholine
receptors. They cause ACh release in several brain regions, including the
striatum, nucleus accumbens, medial thalamus, and interpeduncular nucleus.

Cocaine and Amphetamines are abused primarily as spree drugs.

Cocaine can be used with morphine and other opiates in a mixture called a
speedball.

Disease/Outcome
Cocaine
a. Cardiovascular
- Hypertension, Myocardial Infarction, Angina, Chest Pain, Supraventricular
tachycardia, ventricular dysrhythmias, cardiomyopathy, cardiovascular
collapse from bodypacking rupture, moyamoya vasculopathy, left ventricular
hypertrophy, myocarditis, sudden death, aortic dissection
b. Endocrine/ Reproductive
- Diabetic ketoacidosis
c. Hepatic
- Ischemic necrosis, hepatitis
d. Neurologic
- Stroke, seizure, status epilepticus, headache, delirium, depression,
hypersomnia, cognitive deficits
e. Other Gastrointestinal
- Ischemic bowel, colitis
f. Prenatal and Perinatal
- Placental abruption, teratogenesis, neonatal irritability
g. Perioperative
- Hypersomnia, and depression in withdrawal, mimicking of postoperative
neurologic complications, complication from underlying drug-induced
cardiopulmonary disease
h. Pulmonary
- Nasal septum perforation, Gingival ulceration, perennial rhinitis, sinusitis,
hemotysis, upper airway obstruction, fibrosis, hypersensitivity pneumonitis,
epiglottitis, pulmonary hemorrhage, pulmonary hypertension, pulmonary
edema, emphysema, interstitial fibrosis, hypersensitivity pneumonia
i. Renal
- Rhabdomyolyis and acute renal failure, vasculitis, nectrozing angiitis,
accelerated hypertension, nephrosclerosis, ischemia
j. Sleep
- Hypersomnia in withdrawal
k. Trauma
- Death during Russian roulette
l. Musculoskeletal
- Rhabdomyolysis
Opiates
a. Endocrine/Reproductive
- Osteopenia, alteration in gonadotropins, decreased sperm motility, menstrual
irregularities
b. Hepatic
- Granulamatosis
c. Infectious
- Aspiration pneumonia
d. Neurologic

e.
f.
g.
h.
-

Seizure, (overdose and hypoxia), compression neuropathy

Other Gastrointestinal
Constipation, ileus, intestinal pseudo-obstruction
Prenatal and Perinatal
Neonatal abstinence syndrome, including seizure
Perioperative
Withdrawal, inadequate analgesia
Pulmonary
Respiratory depression/failure, emphysema, bronchospasm, exacerbation of
sleep apnea, pulmonary edema
i. Renal
- Rhabdomyolysis, acute renal failure, factitious hematuria
j. Sleep
- Insomnia
k. Trauma
- Motor vehicle rash, other violent injury
l. Musculoskeletal
- Osteopenia
Cannabis
a. Cardiovascular
- Increases heart rate, variable effect on blood pressure, vasodilation,
increases cardiac output (heart rate increases and/or peripheral resistance
decreases), promotes myocardial ischemia by increasing myocardial demand
and decreasing O2 delivery (increases carboxyhemoglobin), worsens angina
pectoris and promotes acute coronary syndromes.
Amphetamines
a. Cardiovascular
- Increases blood pressure, increases heart rate (with sharp increases of blood
pressure may have reflex slowing), promote thrombosis, acute myocardial
infarction, aortic dissection, left ventricular hyperthrophy and dilation
(myocarditis/cardiomyopathy), arrhythmias, pulmonary, hypertension, stroke,
sudden death
Outcomes:
a. Biologically Based Factors (generic, neurological, biochemical, and so on)
- More use to achieve intoxication (warning signs of abuse absent)
- Easier to reach the addictive level
- Easy deterioration of cerebral functioning, impaired judgment, and social
deterioration
- Feeling overwhelmed or stressed
- Feeling attacked or panicked; need to avoid emotion
- Failure, low self-esteem, or isolation
- Need to self-medicate againstloss of control or pain of depression;
inability to calm down when manic or to sleep when agitated
b. Psychosocial /Developmental Personality Factors
- Need to blot out pain, gravitate to outsider groups
- Need to blot out pain; use of a stimulant as an anti-depressant
- Anxiety and guilt
- Chronic depression, anxiety, or pain
- Nightmares or panic attacks

c. Social and Cultural Environment

- Easy frequent use
- Sanction; no conflict over use
- Pervasive sense of abandonment, distrust, and pain; difficulty in
maintaining attachments
- Reinforced, hidden abusive behavior that can progress without
interference
- Belief that most people use or favor use or think its cool to use
- Need to alleviate or escape from stress via chemical means
- Painful sense of aloneness, normlessness, rootlessness, boredom,
monotony, or hopelessness
- Stress without buffering support system
Treatment
1. Screening
2. Intake
3. Assessment
4. Formulation of a treatment Plan
5. Individual, Group and Family Treatment
6. Vocational Reentry
-

Behavioral Therapy
Counseling
Psychotherapy
Cognitive therapy
Others (i.e., methadone, LAAM [l--acetyl- methadol] , nicotine patches,
and nicotine gums)
Treat co-occuring mental disorders (i.e., antidepressants or mood
stabilizers).
From indirect problems, such as the need for housing, legal and financial
services, educational and vocational assistance, and family/child care
services.
Such as needs are often shaped by the gender, age, race, culture, and
sexual orientation of the abuser.
CASE STUDY
Robert grew up in a suburban, middle-class family. His father was an administrator
at the local Navy base and his mother was a housewife. He had two older sisters. He
remembers his childhood as decent. His father was strict and everyone felt afraid
of him, but he did not actually hit the children. His mother was basically good to
him, though she did not control everyone through guilt. School was alright, but
Robert recalls always feeling a little different than the other children. He just
never felt comfortable in his own skin. Something vague was bothering him, as if
something bad was about to happen. This discomfort did not leave him for any long
periods of time. He definitely recalls at age 10, he was seeking something to make
the discomfort go away.
Robert started using alcohol at age 12. In junior high school, he began to hang out
with older students and was introduced to other drug use. By the end of high
school, he had experimented with cocaine, LSD,marijuana, etc. By college, he had
settled into daily use of alcohol and tranquilizers. He obtained the alcohol by

figuring out which stores would sell to underage customers. He obtained the
tranquilizers legally by figuring out which doctors would give him drug
prescriptions if he complained about nervousness.
By age 30, he was fired from his third sales job because of lateness, emotional
outbursts, and inattention to his work. His boss was Robert as personable,
intelligent, and with great potential- but completely unpredictable. By age 30,
Robert had become not only unpredictable to boss: he had become unpredictable to
himself. His drug addiction had him cycling through periods of exhaustion, fear,
disorientation, and panic attacks, with only brief episodes of relief. This relief would
come immediately after drinking or taking pills. Unfortunately, the relief would wear
off quickly, and he would be back to fear again.

Stages of addiction
Early stages of addiction
marked by the acceptance of chemicals as a way to change feelings. The
early stage of the addictive cycle is:
1. Unsafe feelings
- Light-headedness, shakiness, heart palpitations, mental racing, confusion,
extreme self-consciousness, felling alien to your environment, ad generalized
anxiety. These are all forms of human vulnerability.
I feel like I dont have any skin
2. Mental focus on the unsafe feelings
- Severe despair over any criticism, worrying something bad was about to
happen, and sensing he was about to get in trouble. To cope with these
feelings, people would figure out ways to stay away from situations that
increased vulnerability.
Robert would try to avoid going to school by complaining of stomachaches to his
mother.
3. A desire to get rid of the feelings
- The desire to get rid of these feelings by using chemicals (e.g. marijuana,
cocaine, etc.) to make him feel good, but in fact it is being used to stop
feeling bad.
Looking for something
4. Using chemicals to get rid of the feelings
- There is a moment of relief through chemicals.
age of 12, he was introduced to drugs and he felt at ease. the first time I felt
like one of the guys
5. Nervous system disturbance because of the chemicals
- The disturbance of his nervous system produced a recurrence of unsafe
feelings. Learning that he could feel right again if he used the chemicals, he
uses them again to get of the unsafe feelings
Age 12, he would be sick the next day. He convinced his friends to get some beer
at lunch hour on school day.
6. Unsafe feelings
- Once the association between unsafe feelings and chemical use has been
established, a person had taken a turn away from learning coping skills

(healthy responses that help a person through difficult situations) and toward
Addiction.
Middle Stage of Addiction
marked by the immediate use of chemicals in response to difficult
feelings.
The middle stage of the addictive cycle is:
1. Unsafe feelings
2. Using chemicals to get rid of the feelings
- Increase in amount and frequency.
3. Nervous system disturbance because of the chemicals
- The cycle of chemical use and nervous system disturbance reinforce each
other.
4. Unsafe feelings
Late Stage of Addiction
1. Nervous system disturbance
- Robert would get up in the morning to go to work with his nervous system
trying to recover from late night drinking.
2. Using chemicals
- He knew he could not go to work feeling so nervous. He would take several
tranquilizers just to shave, shower, and get dressed. Then he would drink
coffee to get some energy.
3. Nervous system disturbance
- Sensing something bad was about to happen, he would feel like at a child in
a world of adults.
Stages
-what started as the answer to unsafe feelings has become the cause of unsafe
feelings. The neurological damage is manifesting in constant instability, mental
terrors and hallucinations, and inability to function at simple tasks. The person loses
everything-except addiction.
1. Relief
- Refers to the relief from using a drug, which allows a potential addict to
escape one or more of the following feelings: boredom, loneliness, tension,
fatigue, anger and anxiety.
2. Increased Use
- Involves in taking greater quantities of the drug
3. Preoccupation
- Consists of a constant concern with the substance- that is, taking the drug
becomes normal behavior.
4. Dependency Phase
- Synonymous with addiction
5. Withdrawal
- Physical and/or psychological effects derived from not using the drug;
involves such symptoms as, itching, chills tension, stomach pain, or
depression from the non-use of the addictive drug and/or an entire set of
psychological concerns mainly involving an insatiable craving for the drug.

Causes:
1. Searching for pleasure and using drugs to heighten good feelings
2. Taking drugs to temporarily relieve stress or tension or provide a temporary
escape for people with anxiety
3. Taking drugs to temporarily forget ones problems and avoid or postpone
worries
4. Viewing certain drugs (such as alcohol, marijuana and tobacco) as necessary
in order to relax after a tension-filled day at work
5. Taking drugs to fit in with peers, especially when peer pressure is strong
during early and late adolescence; seeing drugs as a rite of passage
6. Taking drugs to enhance religious or mystical experiences (very few cultures
teach children how to use specific drugs for this purpose)
7. Taking drugs to relieve pain and some symptoms of illness
8. To perceive some psychological advantage in using these compounds at least
initially
- People will experience chronic depression, feel intense job pressures, are
unable to focus on accomplishing goals, or have a sense of inferiority may
find a stimulant such as cocaine or amphetamines to provide a solution to
such dilemma. These drugs cause a spurt of energy, a feeling of euphoria, a
sense of superiority and imagined confidence.
- People will experience nervousness and anxiety and want instant relief from
the pressure of life may choose a depressant such as alcohol or barbiturates.
These agents sedate, relax, provide relief, and even have some amnesiac
properties allowing users to suspend or forget their problems.
- People who perceive themselves as created may select a hallucinogens type
of drug to expand their minds, heighten their senses, and distort the
confining nature of reality.
Drug
Class
Action

Sedative/Hypnotics (Depressants)

Desired
Effects
Common
problems
Withdraw
al
Symptom
s
Examples

Similar to alcohol, reduction of anxiety, elation or excitement

secondary to depression of inhibitions and judgement.
Tolerance, physical dependence, respiratory depression with overdose

DEA
Schedule

Mechanism vary; generally produce a reversible depression of the

central nervous system possibly secondary to a decreased turnover of
dopamine and serotonin in specific brain areas; block stress-induced
acceleration or norepinephrine turnover.

Physical symptoms similar to those of alcohol withdrawal, seizures,

anxiety, altered perceptions, severity and difficulty vary with half-life
of drug
- Benzodiazepines
- Barbiturates
- Methaqualone
- Meprobamate
- Chloral Hydrate
Schedule 1
- Methaqualone (Quaaludes)

Schedule 2
- Pentobarbital (Nembutal)
- Amobarbital (Amytal, Tuinal)
- Secobarbital (Seconal, Tuinal)
Schedule 3
- Glutethimide
- Butabarbital (Butisol)
- Butalbital (Fiorinal)
Scheudle 4
- Meprobramate (Equanil, Miltown)
- Chloral hydrate
- Alprazolam (Xanax)
- Chlordiazepoxide (Librium)
- Diazepam (Valium)
- Flurazepam (Dalmane)
- Iorazepam
Treatment
The best treatment programs provide a combination of therapies and other services
to meet the needs of the individual patient.
Core components of addiction treatment:
- Intake processing/assessment
-Treatment planning
- Clinical and case management
- Substance use monitoring
- Behavioral therapy and counseling
- Pharmacotherapies
- Self-help/peer support groups
-Continuing care
Ancillary services include:
- Mental health services
- Medical services
- HIV/AIDS services
- Educational services
- Vocational services
- Legal services
- Financial services
- Housing/transportation services
- Family services
- Child care services
1. Detoxification
- Attenuation of the physiologic and psychological features of withdrawal
syndromes
- Process of interrupting the momentum of compulsive use in persons
diagnosed with substance addiction.
- Process of withdrawing from chemical use.
- Acupuncture is effective for easing the physical discomfort of detoxification
from drugs as diverse as heroin, and for restoring energetic balance to the
entire physiological system.

2. Hospital Settings
- For patients who
cannot be treated safely in an outpatient or emergency department
setting because of acute intoxication, severe or medically complicated
withdrawal potential
has co-occuring medical or psychiatric conditions that complicate
detoxification or impair treatment engagement and response
Fails to engage in treatment at a lower level of care
Has a Life-or limb-threatening medical condition that would require
hospitalization.
A. Partial Hospital Programs and Intensive Outpatient
- Considered for patients who require intensive care but have a reasonable
chance of making progress on treatment goals in the
Rehabilitation facilities:
A. Intensive outpatient rehabilitation programs
are partial hospitalization or day programs that allow the client to work or
attend school while spending 15 to 30 hours per week at the treatment
center.
B. Halfway houses
residential therapeutic environments where individuals who have completed
a rehabilitation program may live while pursuing employment or working.
C. Long-term care facilities
residential settings for individuals who are socially and psychologically
unprepared to be self-supporting in the community.
Detoxification
Therapeutic Communities
- Residential treatment program for drug dependency.
- Program that advocates a complete change in lifestyle, such as complete
abstinence from drugs, elimination of deviant behavior, and development of
employable skills.
Outpatient treatment
- Denotes a nonresidential setting where treatment takes place using support
groups to counter life stress.
- Can involve any number of individual, group, or family sessions that the client
attends one or more times per week.
- -includes twelve step-style groups, interactive group therapy, confrontational
groups, support and relapse prevention, occupational counseling, and so on.
- Outpatient treatment in which the client is present 10 to 30 hour per week is
usually called intensive outpatient treatment, day treatment, or partial
hospitalization.
Treatment services
Certified Qualified Counselors
Patient Placement Criteria
- A system that allows the referring professional to match the assessed level of
addictive severity with an appropriate intensity and level of care, ranging
from an outpatient clinic to a medical center.

References:
Clinical Manual of Substance Abuse Jean Kinney 1991 Mosby-Yearbook
Inc
Neurobiology of Addiction George F. Koob, Michel Le Moal 2006 Elsevier
Inc
Addiction Medicine 4th Ed Richard Ries etal 2009 Aptara Inc
Healing Addiction (The Vulnerabiity Model of Recovery Bonney Schaub &
Richard Schaub997 Delmar Publishers
Drugs and Society 7th ed- Glen Hanson etal 2002 Jones and Burtlett
Publications
Basic Pharmacology in Medicine 2nd ed Joseph R. DiPalma- 1982 Kosaido
Printing
Basic and Clinical Pharmacology Bertram Katzung- 1992 Appleton and
Lange
Basic Pharmacology in Medicine 3rd ed Joseph DiPalma &John DiGregorio
1990 McGraw Hill Book Co