Drug Abuse

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 ________________________________________________________________ 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 1. 2. 3. 4. 5.

Euphoria Alertness Increase motor & speech activity ä appetite ( amphetamine) ã sympathetic activity: Ó HR , Ó BP, Ó respiration

Withdrawal symptoms 1. 2. 3. 4. 5.

Depression Sleepiness Fatigue ã appetite ( amphetamine) Bradycardia

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 1. 2. 3. 4.

Withdrawal symptoms

Anxiolytic Mild stimulant Increased alertness Increased attention & memory

1. Anxiety 2. Depressed mood 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 _______________________________________________________________________ _ 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 _____________________________________________________________ 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 _________________________________________________________________ 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 _______________________________________________________________________ _ 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 ____________________________________________________________________ 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