Pharmacology & Toxicology

Department
Dr. Mariam Yousif
23rd December, 2006
 1. To define drug abuse, drug dependence, tolerance
and withdrawal or abstinence syndrome.
2. What are the main drugs of abuse?
3. Identify the pharmacological approaches to treating
drug dependence.
4. Identify the properties and treatment of some abused
drugs.
a. Opioids
b. Other abused drugs: Ethanol, Nicotine, Barbiturates,
Amphetamine, Cocaine, Cannabinoids
 Drug Abuse
-Drug abuse means any recurrent use of
substances that are illegal, or that cause
harm to the individual.

-Drugs of abuse form an extremely

heterogeneous pharmacological group.
What links them is that people find their
effect pleasurable (hedonic) and tend to
want to repeat it.
 Drug Dependence
-Dependence is defined as a compulsive
craving that develops as a result of
repeated administration of the drug. It
describes the state when drug-taking
becomes compulsive, taking precedence
over other needs.

-The common feature of dependence-

producing drugs:
They have a positive reinforcing action
('reward') associated with activation of
Dependence is often associated
with

• Tolerance

• Physical abstinence syndrome

• Psychological dependence (craving)

 Tolerance
Is the decrease in pharmacological effect
on repeated administration of the drug,
often accompanies the state of
dependence.

Withdrawal or abstinence
syndrome
Describes the adverse effects, both
physical and psychological of stopping
taking a drug.
 Psychological dependence
(craving)

Seen when a drug is used repeatedly

because it provides a psychological
reward of some kind, whether of
pleasure or freedom from pain and
anxiety.
 What are the main drugs of abuse?
Drugs that are abused have a wide variety
of pharmacologic actions.

Very loosely divided into at least four

categories:
depressants,
stimulants (excitant),
opioids &
hallucinogenic.
Depressants
Drugs categorized to reduce activity in the CNS
to the point, in the case of drugs such as
barbiturates and general anesthetics, of coma
and death.

Stimulant drugs
Induce alertness, excitement and euphoria.
 Opioid drugs
Are agonists at the opioid receptors
and produce a mix of actions,
produce euphoria and also have
depressant actions.

Hallucinogenic drugs
Produce altered perception
especially with respect to time and
space and related to this is their
ability to produce hallucinations.
The Main Drugs of
Abuse
Type Examples Dependenc
e Liability
Narcotic analgesics Morphine Very strong
Diamorphine Very strong
General CNS Ethanol Strong
depressants Barbiturates Strong

Anxiolytic drugs Benzodiazepin Moderate

es
Psychomotor Amphetamines Strong
stimulants Cocaine Very strong
Nicotine Very strong
Psychotomimetic LSD Weak or
agents Cannabis absent
 The extent, onset and duration of
the effects are very dependent upon
the route of administration and
pharmacokinetic properties.

To achieve the greatest effect most

rapidly,
the intravenous route is used
 Nasal administration
(especially cocaine and nicotine)

Absorption into arteries and veins is very

rapid and avoids first-pass exposure in
the liver.
An analogous route is by inhalation into
the lungs in the form of smoke and this is
used especially for opiates.

The oral route, while being the easiest, is

often not the favorite one since it involves
an unavoidable delay between ingestion
and effect.
 Morphine in various forms

LSD in pill forms

Coca leaves and powder
Hashish oil

Heroin in white powder form

Marijuana
seeds
Marijuana Cannabis
 Pharmacological Approaches To
Treating Drug Dependence
Mechanism Examples
Substitution, to alleviate Methadone, used short-term to
withdrawal symptoms blunt opiate withdrawal.
Benzodiazepines, to blunt alcohol
withdrawal.
Long-term substitution Methadone substitution for opiate
addiction.
Nicotine patches or chewing
Blocking response gum Naltrexone to block opiate
effects.
Mecamylamine to block nicotine
Aversive therapies effects.
Disulfiram to induce unpleasant
response to ethanol.
Modification of craving Bupropion (antidepressant)
Naltrexone (blocks opiate
receptors).
 Properties of Abused Drugs
a. Opioids

Opioids are well known as drugs of

dependence.

Abusers of opioids can show tolerance

and psychological dependence to opiate
effects and in addition show withdrawal
when opioids are discontinued after
regular use.
 Properties of opioids abuse
Analogs: morphine, heroin, methadone.

Desired psychological actions: euphoria,

analgesia, relaxation.

Pharmacologic actions/ effects of

overdose: confusion, respiratory
depression.
 Properties of opioids abuse

Psychological dependence: marked and

develops rapidly if intravenous route
used.

Tolerance: very marked.

Withdrawal symptoms
Withdrawal from morphine, heroin, codeine:
peak abstinence at 36-72 hours
 Withdrawal symptoms
Early symptoms (10-12 hrs) include: rhinorrhea,
perspiration, lacrimation and yawning.

Intermediate symptoms (18-24 hrs) include:

mydriasis, anorexia, muscular tremors.

Peak symptoms (36-72 hrs) include:

restlessness, hot flashes alternating with chills,
increase in blood pressure and heart rate,
increases in rate and depth of respiration, fever
of 10 or more, nausea, vomiting, diarrhea.
Withdrawal from an opioid is generally not life
threatening although almost unbearable.
Treatment of opioid dependence

Detoxification is the same for all drugs

that produce physical dependence.

This involves substituting a longer-

acting, orally effective,
pharmacologically equivalent drug for
the abused drug.

The patient is stabilized on the

 Treatment of opioid dependence

-The management of opioid

dependence requires medical, social
and psychological treatment. Access
to a multidisciplinary team is
valuable.

Methadone
Naltrexone
Lofexidine
 Methadone

Is an opioid agonist, can be

substituted for opioids such as heroin
and morphine, preventing the onset of
withdrawal symptoms.

It is administered in a single daily

dose usually as methadone oral
solution. The dose is adjusted
according to the degree of
dependence with the aim of gradual
reduction.
 Methadone

Has slower metabolism and slower

excretion, produces less marked
effects; therefore it is used as
morphine and heroin opiate
replacement.

Drugs that are slowly eliminated from

the body generally show limited
withdrawal effects.
Naltrexone
It is an opioid antagonist, blocks the
action of opioids and precipitates
withdrawal symptoms in opioid-
dependent subjects.

Lofexidine
Is used for management of symptoms of
opioid withdrawal. Like clonidine, it is an
alpha-adrenergic agonist and acts
centrally to produce a reduction in
sympathetic tone.
b. Properties of other abused drugs
Ethanol (Alcohols)

Analogs: most important is ethanol,

others also abused like methanol.

Route: oral.
 Ethanol (Alcohols)
Pharmacologic actions/effects of overdose
Excitement, confusion, ataxia, coma and death
with acute overdose.

Chronic abuse leads to hypertension, and

cardiac, brain and liver pathology.

Ethanol consumption during pregnancy:

Damaging to the fetus; fetal alcohol syndrome
(FAS): impaired fetal development, small size,
abnormal facial development, mental
retardation.
 Withdrawal symptoms
Can be fatal, convulsions,
seizures, hallucinations (pink
elephants).
A normal liver is shown grossly for
comparison

Hepatocellular carcinoma is arising

here in a liver with micronodular
cirrhosis as a consequence of chronic
 Treatment of alcohol dependence
Disulfiram
It is used as an adjunct to the treatment
of alcohol dependence.

It gives rise to extremely unpleasant

systemic reactions after the ingestion of
even small amount of alcohol because it
leads to accumulation of acetaldehyde in
the body.

Flushing of the face, throbbing

Metabolism of
Mechanism of action of Disulfiram

Ethanol

Alcohol dehydrogenase

Acetaldehyde

Disulfiram Aldehyde dehydrogenase

(-)

Acetic acid
 Treatment of alcohol dependence

Benzodiazepines
Used to attenuate withdrawal
symptoms, but they also have a
dependence potential, administration
should be for a limited period only.

Acamprosate
To reduce craving, recently introduced.
 Nicotine Dependence
Forms of use: smoked tobacco in
cigarettes, cigars, pipe, intra-nasal as
snuff, chewing tobacco (buccal cavity),
chewing gum for treating nicotine
addiction.

Type of action: stimulant.

 Harmful effects of smoking
# Smoking accounts for about 10% of
deaths worldwide, mainly through:
- cancer, especially lung cancer.
- ischaemic heart disease.
-chronic bronchitis.

# smoking in pregnancy: reduces birth

weight and retards child development,
increases abortion rate.
 Lip Cancer
Smoking cigarettes and cigars has left this
tobacco addict with cancer on his lip.

Black Lung
This is what lungs would look like after
smoking for ten years
The normal gross Small cell carcinoma of the lung
appearance of a lung in appears here in a smoker. Smokers
cross section shown for who stop will diminish their risk for
comparison. lung cancer, even after just a couple
of years.
 Nicotine

Pharmacologic actions/effects of
overdose
Associated with cancer (principally in
lungs and oral cavity), smoking
specifically results in emphysema,
bronchitis and cough.

Withdrawal symptoms: irritability,

headache, weight gain.
 Treatment
Nicotine replacement therapy and
bupropion

Effective aids to smoking cessation for

those smokers more than 10 cigarettes a
day.

Nicotine products available as nicotine

chewing gum (also available in citrus and
mint flavour),
self adhesive patches and also as lozgens.
Bupropion (Amfebutamone)
Adjunct to smoking cessation in
combination with motivational support.

Available as tablets 150mg.

 Barbiturates

-Type of action: depressant.

-Pharmacologic actions/effects of
overdose: sedation, confusion, coma,
respiratory depression resulting in
death.
 Amphetamine

-Type of action: stimulant.

-Desired psychological actions: euphoria, arousal
and increased state of wakefulness.

-Effects of overdose: psychosis, cardiovascular

death (arrhythmias and hypertensive crisis),
hyperthermia.

-Withdrawal symptoms: depression, sleep

disturbance.
 Cocaine
-Route: oral, nasal, smoked, i.v.

-Type of action: stimulant.

-Effects of overdose: psychosis, cardiovascular

death (arrhythmias and hypertensive crisis),
fetal damage.

-Withdrawal symptoms: depression, sleep

disturbance.
 Cannabinoids
Cannabis (Marihuana)

-Main active constituent is

∆9-Tetradydrocannabinol (THC).

-Route: oral or smoked.

-Type of action: weak hallucinogen. THC

also shows analgesic and antiemetic
activity.
 Cannabinoids
Nabilone
A THC analogue, developed for its
antiemetic property.
Indicated for treatment of nausea and
vomiting caused by cytotoxic
chemotherapy, unresponsive to
conventional antiemetics.
 DRUG LIST
,Methadone, Benzodiazepines
,Naltrexone, Mecamylamine
,Disulfiram, Acamprosate
,Bupropion, Clonidine
,Lofexidine, Cannabis
,Nabilone, Ethanol
Amphetamine, Cocaine
THANK YOU