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Drug Abuse

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  1. Drug Abuse Self administration of drug or drugs in manner not in accord with accepted medical or social patterns

  2. Drug Abuse • Psychological Dependenc (Habituation) addiction. • Drug necessary to maintain user’s sense of well-being • Physical Dependence, dependence • Physical symptoms if intake is reduced

  3. Addiction Compulsive, relapsing drug use despite negative consequences, at times triggered by cravings. • Includes • Tolerance (dose has to be progressively increased to maintain rewarding or analgesic effect) • Psychological dependence • Physical dependence • Compulsive use

  4. Molecular Mechanism of Action • Mesolinbic dopamine system is the prime target of addictive drugs. • The system originates in the ventral tegmental area (VTA). • Drug of abuse are rewarding and reinforcing.

  5. Classification of drugs of abuse • Drugs that activate G Protein-Coupled Receptors Opioids Cannabinoids γ-hydroxybutyric acid (GHB) LSD, mescaline • Drugs that bind to ionotropic receptors and ion channels Nicotine Alcohol Benzodiazepines Phencyclidine, ketamine

  6. Drugs that bind to transporters of Biogenic Amines Cocaine Amphetamine Ectasy

  7. Opiates are drugs that are derived from the Poppy Plant and are Central Nervous System (CNS) depressants. • The most common opiates are: • Opium • Heroin • Morphine • Codeine • Opiates are known by several different names: OPIATES • Smack • Soapium • Chiva • Poppy • Flower • Hazel • Morf • H

  8. Narcotics • Examples • Opium • Morphine • Heroin • Codeine • Oxycodone (Percodan) • Meperidine (Demerol) • Propoxyphene (Darvon) • Talwin • Fentanyl

  9. Mechanism of Action • Acts on μ, κ and delta opioid receptors

  10. Effects • Analgesia • CNS depression • Euphoria • Drowsiness • Apathy • Antidiarrheal action • Antitussitive action

  11. Opiates adverse effects • Absence of Stress • Altered Mental Process • Liver Damage • Nausea/Vomiting • Collapsed Veins • Kidney Damage • Lung Damage • Sleepiness • Constipation • Brain Damage • Immune System Damage • Itchy Skin • Menstrual Irregularities • Impaired Vision • Loss of Sex Drive • Overdose/Death

  12. Narcotics • Overdose • Mild to Moderate • Lethargy • Pinpoint pupils • Bradycardia • Hypotension • Decreased bowel sounds • Flaccid muscles • Severe • Respiratory depression • Coma • Aspiration • Seizures with certain compounds (meperidine, propoxyphene, tramadol)

  13. Narcotics • Overdose • Management • Naloxone • Treatment of opioid addiction • Long acting opioids

  14. Narcotics • Withdrawal • Insomnia • Restlessness • Irritability • Anorexia • Tremors • Back, extremity pain • Watery eyes • Yawning • Rhinorrhea • Sneezing • Diarrhea • Diaphoresis Resembles Severe Influenza

  15. Cannabinoids • Marijuana (Tetrahydrocannabinol (THC) Endogenous cannabinoids (Anandamide) Act on CB1 receptors, presynaptically and inhibit the release of glutammateor GABA Leading to disinhibition of dopamine neurons. Onset of effects: within minutes Effects: Euphoria, relaxation, visual distortions, drowsiness, diminished coordination and memory impairment.

  16. Hallucinogens • LSD • Mescaline • Psilocybin

  17. Produce altered/enhanced sensation • Increased dose does not intensify effect • Mechanism of action • Act on 5HT2A receptor------G proteins ------ IP3 ---intracellular calcium-------- increase glutamate release.

  18. Signs and symptoms • Anxiety, excitement • Nausea, vomiting • Tachycardia, tachypnea

  19. Hallucinogens • Moderate Intoxication • Tachycardia • Mydriasis • Diaphoresis • Short attention span • Tremor • Hypertension • Hyperreflexia • Fever

  20. Hallucinogens • Life-threatening toxicity (rare) • Seizures • Severe hyperthermia • Hypertension, arrhythmias • Agitated • Diaphoretic, hyperreflexic • Untreated hyperthermia can lead to hypotension, coagulopathy, rhabdomyolysis and multiple organ failure

  21. Drugs that mediate their effects via ionotropic receptors • Nicotine • Smoking of tobacco through different routes. • Agonist of nicotinic acetylcholine receptor (nAChR),role in cognitive processes. • Rewarding effect of nicotine requires involvement of VTA in which (nAChR) are expressed on dopamine neurons. • Nicotine withdrawal : irritability, sleep problems.

  22. Treatment • Slowly absorbable form of nicotine. • Cytisine, varenicline (partial agonists) • Act by occupying nAChRs on dopamine neurons of the VTA. • Bupropion + behavioural therapy

  23. Benzodiazepines and barbiturates • Anxiolytic and sleep medications • Abused for their EUPHORIC effects • GABAA receptors on interneurons, disinhibition of mesolimbic dopamine system-----rewarding effects. • Withdrawal symptoms include • Irritability, insomnia, photophobia, depression, muscle cramps and even seizures.

  24. Ketamine and Phencyclidine • General anesthetic • Non-competitive antagonism of NMDA receptor. • Increased blood pressure, impaired memory function & visual alterations. • ‘Club drugs’ and sold as ‘angel dust’

  25. Phencyclidine (PCP) • Street names • Angel dust • Peace Pill • Hog • Krystal • Animal tranquilizer • Used as veterinary anesthetic

  26. Inhalants • Examples • Nitrates , ketones , aliphatic and aromatic hydrocarbons • Gases (freon, halon fire extinguishing agent) • Metallic paints • Sniffing • Huffing • Bagging

  27. Drugs that bind to transporters of biogenic amines • Examples • Cocaine • Amphetamines • Benzedrine (bennies) • Dexedrine (dexies, copilots) • Methamphetamine (ice, black beauties) • Ephedrine • Caffeine • Ritalin

  28. Cocaine local anesthetic used to treat depression Block of dopamine transporter, by increasing conc in nucleus accumbens Increased risk of intracranial haemorrhage, ischemic stroke, myocardial infarction and seizures.

  29. Amphetamines • Produce • euphoria • hyperactivity • alertness • sense of enhanced energy • anorexia

  30. Stimulants • Overdose signs/symptoms • Euphoria, restlessness, agitation, anxiety • Paranoia, irritability, delirium, psychosis • Muscle tremors, rigidity • Seizures, coma • Nausea, vomiting, chills, sweating, headache • Elevated body temperature • Tachycardia, hypertension • Ventricular arrhythmias

  31. Stimulants • Withdrawal • Drowsiness • Profound depression (“cocaine blues”) • Increased appetite • Abdominal cramps, diarrhea, nausea • Headache

  32. Ectasy • Include derivatives of amphetamine related compound methylene-dioxymethaamphetamine (MDMA) • Increases extracellular concentration of serotinin • Long term cognitive impairement in heavy users of MDMA. • Withdrawal lead to depression

  33. Treatment of addiction • Transdermal nicotine patches for smoking • Baclofen is a GABAB receptor agonist • Rimonabant is inverse agonist of CB1 receptors