Drug abuse

What is meant by drug abuse?

 Excessive use of a drug for non medical purposes
The drug may be
1. A legal drug: e.g. benzodiazepines
2. An illegal drug: e.g. Heroin & LSD
3. A chemical which is not considered by public as a drug: e.g. Nicotine in cigarette
smoking

What is meant by reinforcing properties?

 They are properties of a drug that motivate the individual to abuse it. It may be:
Positive reinforcing properties:
 Production of pleasure
 Altering of consciousness
 Body built
Negative reinforcing properties:
 Prevention of withdrawal effects
Abuse potential from any drug depend on its reinforcing properties
Cocaine & Opioids : High abuse potential
Marijuana: Low abuse potential

What is meant by psychological dependence?

 A compulsive drug-seeking behavior in which the individual desire to obtain an
additional drug for personal satisfaction in face of known risk to health

What is meant by physiological dependence ?

 The withdrawal of the drug produces symptoms & signs that are opposite to those
caused by a drug.
 Psychological dependence precedes the Physiological dependence.
 Physiological dependence is associated with tolerance

What is meant by withdrawal effects?

A maladaptive behavioural change, with physiological and cognitive concomitants, that
occurs when blood or tissue concentrations of a substance decline in an individual who
had maintained prolonged heavy use of the substance.
What is meant by addiction?
 Recurrent substance abuse by an individual who realize that it is harmful to his
health
 He desire to stop but he can’t
 Obtaining the drug become his primary goal and disrupts the ability to function in
family, social and career settings
What are substances or drugs which are commonly abused?
 Sympathomimetic stimulants
 Tobacco
 Opioids
 Alcohol
 Sedative hypnotics
 Inhalants
 Marijuana
 Hallucinogens
 Anabolic steroids
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Sympathomimetic stimulants
Examples:
Cocaine, amphetamine, Khat (natural alkaloid: Cathinone)
Mechanism
Cocaine: monoamine reuptake inhibitor
Amphetamine: ã release of dopamine from nerve terminals
Sympathomimetic stimulants

Acute pharmacological effects Withdrawal symptoms

1. Euphoria 1. Depression
2. Alertness 2. Sleepiness
3. Increase motor & speech activity 3. Fatigue
4. ä appetite ( amphetamine) 4. ã appetite ( amphetamine)
5. ã sympathetic activity: Ó HR , Ó 5. Bradycardia
BP, Ó respiration

Adverse effects of chronic abuse :

1. Depression
2. Toxic psychosis
3. Sleep disturbances
4. Cognitive impairment
5. Cardiovascular accidents
6. Cerebrovascular accidents

Treatment:
During period of weaning from stimulants --- treat residual psychotic disorders
• Schizophrenia ---- use neuroleptics
• Depression --- use antidepressants
 Tobacco:Nicotine

Mechanism of action :A Presynaptic nicotine cholinergic receptor agonistà opening of

Na+ channelsà Ó Na+ inflow à neuron depolarizationà Óneurotransmitter release

Acute pharmacological effects Withdrawal symptoms

1. Anxiolytic 1. Anxiety
2. Mild stimulant 2. Depressed mood
3. Increased alertness
4. Increased attention & memory
3. Bradycardia
4. Weight gain

Adverse effects of chronic abuse :

• Cancer
• CVS diseases
• Bronchitis

Treatment
1. Substitution therapy: Nicotine gum or slow-release patches àThe doses are
gradually reduced until the individual is drug free
2. Bupropion: an antidepressant relief symptoms of nicotine withdrawal
3. Varenicline: recently FDA approved
• A partial agonist on acetylcholine nicotine receptors
• Agonist activity à ñrelease of mesolimbic dopamine à òcraving &
withdrawal
• Antagonist activityà reduce smoking satisfaction
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Opioids
Examples:
Heroin, Morphine, Methadone and Meperidine

Mechanism:
Mu & delta opioid receptor agonist

Acute pharmacological effects:

1. Euphoria
2. Warm flushing of skin (Rush - orgasm like reaction)
3. Analgesia
4. Sedation
 5. Respiratory depression

Withdrawal symptoms:
Severe acute syndrome( last 5-7 days after herion withdrawal)
1. Irritability & Hyperalgesia
2. Involuntary movement (kick the habit)
3. Nausea, vomiting & diarrhea
4. ñ sympathetic activity: tachycardia, hypertension, mydriasis &
sweating
5. Rhinorrhea & lacrimation
Delayed syndrome ( up to 6 months)
1. Irritability
2. Insom-nia
3. Craving

Adverse effects of chronic abuse :

1. Decrease life expectancy
2. Increase risk of HIV infection in IV users

Treatment
Short term therapy
1. Substitution therapy: Management of opioid withdrawal symptoms
Substitute methadone (long acting opioid )for heroin ( short acting opioid) for short term
followed by a gradual tapering
2. Rapid detoxification: precipitation of opioid withdrawal symptoms by using
opioid antagonist
Naloxone or naltrexone + clonidine+ adjuvant medication (e.g. sedative ,analgesic)

Long -Term management

1. Methadone can be administered in stable doses for long period ( not less than 6
months)
Advantage of methadone use in addict
a. It is taken orally
b. It has a long duration of actionà avoid up & down effect of heroin
c. Decrease craving
d. Tolerance occur to its sedating effect
e. Block the effect of illicit heroin because of cross tolerance
f. Mild withdrawal manifestation
g. levo-alpha- acetyl methadol: a drug related to methadone taken
3times/weekà better compliance
2. Buprenorphine
a. A partial agonist on mu receptorsà analgesia
b. Block the effect of illicit opioid abuse
c. Safe in overdose: minimal effect on respiratory center
d. Naltrexone : opioid receptor antagonist
 Marijuana

What is it?
 Dried leaves of cannabis sativa plant
 The major psychoactive component is Tetrahydrocannabinol
 Hashish is a partially purified form of Marijuana ( more potent)
 Mechanism: cannabinoid receptors agonist

Acute pharmacological effects:

• Euphoria& uncontrolled laughter
• Abnormal sensory perception (time, hearing & vision)
• Decreased short term memory
• Antiemetic , analgesic & ã appetite
• With large doses: hallucination & motor impairment

Withdrawal symptoms: Rare

• Restlessness & irritability
• Nausea

Adverse effects of chronic abuse :

• Cognitive impairmnet
• Relapse & exacerbation of mental illness

Treatment Behavioral treatments can stop abuse

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Sedative hypnotics
Barbiturates & Benzodiazepines

BZ binds to specific binding sites on GABA-A receptorsà facilitate the action of

GABAà ã chloride conductanceà neuronal hyperpolarization
Barbiturates binds to specific binding sites on GABA-A receptorsà directly ã chloride
conductanceà neuronal hyperpolarization

Acute pharmacological effects:

1. Euphoria & sedation
2. Motor incoordination
3. Impairment of memory
4. At high doses: unconsciousness, respiratory and circulatory failure

Withdrawal symptoms: Excessive CNS stimulation: anxiety, hallucination & seizure

Adverse effects of chronic abuse :
1. Death from drug overdose (when combined with alcohol)
2. Memory impairment
Treatment
If the individual abuse short acting drug --- substitute by long acting one :
Chlordiazepoxide Or Phenobarbital
Then The long acting drug is gradually withdrawn over 2 weeks
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Ethanol

Mechanism of action:
— inhibitory activity of GABA- A receptors
˜ Excitatory activity of glutamate receptors

Acute pharmacological effects:

1. Euphoria & Sedation
2. Anxiolysis
3. Impaired memory & Motor incoordination
High blood alcohol level : Dysphoria , anxiety, mental confusion , loss of consciousness
& respiratory depression

Withdrawal symptoms
1. Shaking ,Sweating & Seizures
2. Nausea & vomiting
3. Delirium tremens: severe agitation, hallucinations & autonomic hyperactivity
(tachycardia & hypertension)

Adverse effects of chronic abuse :

1. Cognitive impairment
2. Liver diseases

Treatment of acute alcohol withdrawal symptoms

• Substitute alcohol with long acting sedative hypnotic: chlordiazepoxide to
control alcohol withdrawal symptoms
• Chlordiazepoxide gradually withdrawn over several weeks

Pharmacotherapy of alcoholism
1. Acamprosate act centrally to restore action of glutaminergic neurons
2. Naltrexone an opioid receptor antagonist ----- ⇓alcohol craving
3. Disulfirm: make the ingestion of alcohol unpleasant by altering the body’s
normal metabolism of alcohol
o Disulfiram inhibit hepatic acetaldehyde dehydrogenaseà acetaldehyde
accumulation à flushing ,throbbing headache, nausea , vomiting &
tachycardia
 Hallucinogens
Examples: Lysergic acids
Mechanism: LSD is a serotonin receptor agonist
Acute pharmacological effects
 Hallucination
 Motor incoordination
 Nausea & vomiting
 ÓHR, BP and body temperature
 appetite

No physiological dependence or withdrawal symptoms

Adverse effects of chronic abuse
 Toxic –psychosis
 Flash backs: re-experience of drug effect long after stop drug use
Treatment:Benzodiazepines for sedation
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Inhalants
1. Solvents (glue, shoe polish, writing correction fluid)
2. Ether
3. Nitrous oxide
4. Acute pharmacological effects: Euphoria –relaxation- hallucination- Flushing
5. Withdrawal symptoms:Increased risk of seizures
Adverse effects of chronic abuse
Solvents
o Cardiac arrhythmia
o Neuropathy
o Hepatoxicity
o Bone marrow suppression
o Pulmonary diseases
Nitrous oxide
Inhalation of pure gas can lead to asphyxia and death
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Anabolic steroids
 Examples Testosterone – nandrolone
 Clinical effects
 No acute behavioral effects
 Increase muscle mass & strength ( if taken with adequate diet & sufficient
physical activity
 Aggression & Hostility
 Changes in libido
 Physical finding:
 hypertrophied muscle
 Elevated liver enzymes
 Hirsutism in females
 Gynecomastia and acne in males