1. Drug of abuse

2. Drug of abuse
Drug of abuse is usually taken to mean the use of an illicit drugs or the excessive or nonmedical use of a licit drug.
A primary motivation for drug abuse appear to be the anticipated feeling of pleasure derived from the CNS effects of the drug.

3. High-yield terms to learn
Abstinence syndrome: term used to describe the signs and symptoms that occur on withdrawal of a drug in a dependent person
Addiction: compulsive drug using behavior in which the person uses the drug for personal satisfaction, often in the face of known risks to health; formerly termed psychological dependence.

4. High-yield terms to learn
Dependence: a state characterized by signs and symptoms, frequently the opposite of those caused by a drug, when it is withdrawn from the chronic use or when the dose is abruptly lowered; formerly termed physical or physiologic dependence

5. High-yield terms to learn
Tolerance: decrease response to drug, necessitating larger doses to achieve the same effect.
Withdrawal symptoms: may be experienced upon discontinuation. Some of these symptoms are generally the opposite of the drug's direct effect on the body.

6. Major groups of drugs that are subject to abuse
Opioids analgesics: Morphine and Heroin
Sedative/hypnotics.
Stimulants.
Hallucinogens
Marjuana
Inhalants
Steroids

7. 1. Opioid analgesics
The most commonly abused drug in this group are heroin, morphine, codeine, oxycodone and among health professionals, meperidine and fentanyl.
The effect of IV heroin are described by abusers as a rush or orgasmic feeling followed by euphoria and then sedation
IV administration is associated with rapid development of tolerance , dependence and addiction.

8. 2. Sedative- hypnotics
The group include ethanol, barbiturates, and benzodiazepines.
Sedative-hypnotics reduce inhibitions, suppress anxiety, and produce relaxation.
All of these action are thought to encourage repetitive use.

9. Sedative- hypnotics (effects)
Flunitrazepam, a potent rapid onset benzodiazepines with marked amnestic properties, has been used in (date rape).
Added to alcoholic beverages, chloral hydrate or ϒ-hydroxybutrate (GABA agonist) also render the victim incapable of resisting rape.

10. Withdrawal
The most important signs of withdrawal derive from excessive CNS stimulation and include anxiety, tremor, nausea and vomiting, delirium and hallucination. Seizures are not uncommon and may be life threating.

11. Treatment of withdrawal
Treatment of withdrawal involves administration of long acting sedative-hypnotics (chlordiazepoxide or diazepam) to suppress the acute withdrawal syndrome, followed by gradual dose reduction.
The opioid receptor antagonist naltrexone reduces alcohol-induced reward (unclear mechanism)
Disulfiram – blockade of ALDH lead to accumulation of acetaldehyde - nausea, flushing, tachycardia, hyperventilation, panic…
Aim: to make alcohol consumption unpleasant and intolerable

12. 3. Stimulants A. Methylxansines
Natural alkaloids occurring in various beverages, namely tea, coffee, cocoa and cola-flavored drinks
Substances: caffeine, theophylline, theobromine
Pharmacological effects:
CNS stimulation tremor, insomnia, and nervousness
Diuresis (vasodilatation of the afferent glomerular arteriole)
Stimulation of cardiac muscle
Relaxation of smooth muscle, especially bronchial.

13. B. Nicotine
It appear to be the only pharmacologically active substances in tobacco smoke
Effects :
In the brain it causes neuronal excitation that can be blocked by Mecamyline
In the spine it inhibits spinal reflex and thus causing muscle relaxation
In the peripheral tissues, nicotine stimulates the receptors at the ganglion and causes tachycardia, hypertension and reduced GI motility

14. Nicotine
Tolerance: to peripheral (not central) ganglionic stimulation, perhaps due to desensitization of receptors
Physical dependence craving : increased irritability, anxiety, impaired performance of psychomotor tasks, aggressiveness and sleep disturbances, headache increased appetite lasts for 2-3 weeks :
Psychological dependence and addiction
Severe toxicity has been described in children who ingest nicotine gum or patches

15. Treatment of Nicotine dependence
Nicotine replacement therapy
Nicotine in patches (controlled release), chewing gums, nasal sprays several times daily (short effect)
Adjunct therapy
Bupropion, TCAs and MAOI
Mecamylamine
Varenicline : nicotinic receptor partial agonist which occlude the rewarding effect of nicotine
Rimonabant:  inverse agonist for the cannabinoid receptor CB1, is also used in smoking cessation

16. C. Amphetamines
Substances: Amphetamine, dextrometamphetamine and methamphetamine
Mechanism of action: Indirect CNS „sympathomimetic“ effect: release of monoamines (noradrenaline, dopamine, or 5-HT) from nerve terminals in the brain
Main effects on CNS:
Locomotor stimulation,
Euphoria and excitement, increased self-confidence, stereotyped behavior, resistance to fatigue, decreased appetite, anorexia

17. Amphetamines
Tolerance develops rapidly to the peripheral sympathomimetic and anorexic effects, but more slowly to the central effects
No clear-cut physical withdrawal syndrome → dependence seems to be a consequence of the unpleasant after-effects (i.e. Fatigue, lethargy, anxiety, depression, hunger) and the effort to avoid them
Full-blown dependence occurs in 5% of users – characterized by strong craving, increased doses, and common uncontrolled ‘runs’)

18. Amphetamines Amphetamine psychosis: Schizophrenic like attack
Chronic abuse can cause necrotizing arteritis leading to cerebral hemorrhage and renal failure.
Therapeutic use: minimal e.g. narcolepsy

19. D. Cocaine The most expensive drug illegally sold
It act by Inhibiting catecholamine Re-uptake
Pharmacological effects are very similar to those of amphetamines but with less psychotic effects
Metabolized in liver and hair deposit of metabolites.
No clear-cut physical dependence syndrome but depression, tiredness and dysphoria coupled with very intensive craving for the drug (strong psychological dependence)

20. 4. Hallucinogens 1. Phencyclidine (PCP)
Antagonist at NMDA receptors.
The most dangerous of the hallucinogenic agents.
Chemically related to ketamine (anesthetic drug) and originally also developed as a drug with this indication
Not so frequent among abusers, unpleasant vegetative effects
Can cause severe delusions and/or hallucination which may turned into the violent behavior
Overdose can cause nystagmus, marked hypertension, and seizures, which can be fatal.

21. 2. LSD (lysergic acid diethylamide)
Exact mechanism is unknown but it is thought ↑firing of 5-HT neurons
Interestingly it dose not cause dependence.
Sympathomimetinc effect
Adverse effects: persistent mental disorder, schizophrenia, injury due to violent behavior

22. 5. Marijuana
Extracts of the hemp plant; originally from Himalaya and Kashmir
Marijuana - dried leaves and flower heads
Hashish - extracted resin
Active substances: cannabinoids (lipophilic non-alkaloid natural compounds)
Routes of administration: mainly inhaled in cigarette smoke

23. Mechanism of action
Through cannabinoid receptors (GPCR type)
CB1- brain;
Mostly localized presynaptically, their activation inhibits neurotransmitter release.
Their paucity in the brain stem → lack of serious respiratory and cardiovascular toxicity.
Endogenous agonist: anandamide
CB2- periphery - immune system (immunosuppressive effects?!)

24. Pharmacological effect
On CNS: combination of psychotomimetic, depressant effect
a feeling of relaxation, well-being and euphoria - without accompanying aggression
Uncontrolled laughing without reason
a feeling sharpened sensory awareness
impairment of motor coordination (driving), short-term memory and judgment. Feeling of time passing slowly, depersonalization; increased appetite
Analgesia, antiemetic action
In high doses: hallucination, paranoia, anxiety

25. Pharmacological effect
Peripheral effects:
vasodilatation (obvious on conjunctive vessels)
tachycardia
Bronchodilation (but opposite may appear during smoking)
reduction of intraocular pressure
Tolerance and physical dependence occur only to a minor degree in heavy users
Withdrawal syndrome: weak and usually mild
irritability, restlessness, confusion, sweating tremor and sleep disturbances

26. Harmful effect
Relatively safe from the viewpoint of acute drug overdose
Problems are rather with chronic use
Somatic effects: decreased testosterone and sperm count
Long-term psychological changes: apathy, impaired memory and decision ability, may promote schizophrenia in pre-disposed patients

27. 6. Inhalants
Certain gases or volatile liquids are abused because they provide a feeling of euphoria or disinhibition.
This group include:
A. Anesthetics
Nitrous oxide, chloroform, and diethylether.
Such agents are hazardous because they affect judgment and include loss of consciousness

28. B. Industrial solvents
Found in gasoline, paint thinners, glues and shoe polish.
Because their ready availability, they are most frequently abused by children in early adolescence.
Are toxic to liver, kidneys, lungs, bone marrow, and peripheral nerves and cause brain damage.

29. C. Organic Nitrites
Amyl nitrite, isobutyl nitrate, and other organic nitrates are referred to as poppers and are mainly used as sexual intercourse enhancer .
Causes dizziness, tachycardia , hypotension and flushing.
With the exception methaemoglobinaemia the adverse effect are usually mild .

30. 7. Steroids
Effect sought by the abusers are increases in muscle mass and strength rather than euphoria .
Adverse effects:
Behavioral manifestation include increase libido and aggression(roid rage)
Severe acne and masculinization in female
Hepatic dysfunction has been reported ,
Increase risk of myocardial infarction
A withdrawal syndrome has been described with fatigue and depression of mood.

31. Good luck