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Stimulants: Cocaine & Amphetamine PowerPoint Presentation
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Stimulants: Cocaine & Amphetamine
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  1. Stimulants:Cocaine & Amphetamine Chapter 6

  2. Cocaine • Coke, Dust, Snow, Flake, Blow, Girl

  3. History of Cocaine • Dates back 5000 years in Peru & Bolivia • Coca leaves (2% cocaine) chewed by Incas • Mid to late 1850s, active ingredient of coca plant extracted by Alfred Nieman

  4. History of Cocaine Popularized in 1880s • Sherlock Holmes (IV cocaine user) • Gave him energy & increased powers of deductive reasoning • Sigmund Freud • advocated cocaine for depression, indigestion, asthma, various neuroses, drug addiction & local anesthetic

  5. History of Cocaine • Prescribed to morphine addicts & alcoholics • Available in patent medicines • Mariani's Coca Wine, mixture of red wine & cocaine • made by Angelo Mariani • received gold medal from Pope (cited as benefactor of humanity) • In U.S. John Pemberton & French Wine Cola - Ideal Nerve & Tonic • mixture of coca leaf & kola nut (caffeine) • Coca Cola

  6. History of Cocaine • In 1906, as many cocaine users in US as in ’76 with only half the population • 1906 Food and Drug Act • Eliminated cocaine from patent medicines & soft drinks • 1903 Coca Cola decocainized Coke • Harrison Narcotic Act of 1914 • Further limited cocaine use & drove up prices

  7. History of Cocaine • Use also declined in popularity because of public sentiment against drug • By 1930s, cocaine pretty much disappeared, but was replaced by amphetamine. • By the late 1970s, coke began a comeback and use levels exploded around 1985….crack

  8. Cocaine: Forms • Coca leaf – < 2% cocaine • Cocaine HCL – Powder • Freebase – Paste • Crack – Rock cocaine

  9. Amphetamine: A Brief History • 1930s U.S. – benzedrine marketed for treatment of asthma, narcolepsy, depression, appetite suppression (bennies) • Also used to keep soldiers alert during combat in WWII • After war, prescribed for fatigue and appetite suppression • Social problems began in 1940s -1950s • Problems continued – particularly students, truck drivers, athletes, businessmen – 75 cents for 1000 tablets in 60s

  10. 1965 – FDA given authority to regulate manufacturing and distribution • But so easily made by amateur chemists, did not work • 1970s – still available, but from illegal manufacturers • 1970s – $5-$10 for 100 tablets – widely used and readily available • Use declined in 1970s and 1980s but now back up – and primarily methamphetamine that is smoked, snorted, injected or taken orally – ice, crank, crystal, speed, meth, chalk

  11. Amphetamine: Forms • Psychostimulant that produces effects in CNS and PNS. It is more potent in CNS. • d-amphetamine • l-amphetamine • methamphetamine • Methamphetamine is more potent than d-amphetamine, which is more potent than l-amphetamine • d-amphetamine used as a prescription medication for ADHD, narcolepsy, and short-term treatment of obesity

  12. “Ice” or “Crank” • Pure d-methylamphetamine HCL • can be smoked because of purity • Started in the West moved east over time • Labs all over Duplin Co. • Very dangerous to synthesize

  13. Routes of Administration • Oral • amphetamine good absorption • cocaine not well absorbed (In the Andes, mixed with ashes) • Intranasally - decent route for cocaine • However, causes blood vessels to constrict, which limits absorption. • intranasal works for amphetamine, but painful • Intravenous - both very effective via this route

  14. Duration of Action Duration of Action • Cocaine - oral onset in 2-3 min with peak in 15-20 min • duration less than 1 hr • IV or smoked - onset in 10 sec & peak in 5-10 min • Amphetamine - oral effects after 30 min & peak in 2-3 hrs • duration 10-12 hrs • IV or smoked - onset 5 min & lasts up to 7 hrs

  15. Actions of cocaine Fowler et al. (2001)

  16. Action of Meth Smoked vs. OralAmphetamine Hours

  17. Cocaine and Neurotransmission • Primary effect on DA & NE with some 5HT influence • Block reuptake • Inhibit MAO

  18. Amphetamine and Neurotransmission • Stimulates release of DA and NE • Blocks reuptake of DA and NE

  19. Biotransformation & Excretion • Drugs have different routes of biotransformation • cocaine broken down in bloodstream • amphetamine broken down in liver • Both are excreted by the kidneys

  20. Physiological & Psychological Effects • Cocaine & amphetamine indistinguishable to IV users • Oral or nasal route - local anesthetic properties would set them apart

  21. Effects on Nervous System • Actions - wide variety of influences on PNS & CNS • Periphery - sympathomimetics • increase BP, HR, body temp, metabolic rate • Increase physical strength & endurance

  22. Central Nervous System • Low or acute doses • increased arousal level & alertness • improve performance on simple tasks • produce mild euphoria • increase of sex drive early on, but reverses with prolong use

  23. High Dose & CNS • Higher doses - (i.e., smoking) • intense feeling of euphoria • described as “whole body orgasm” • hyperactivity • repetitive behaviors - hand clasping, nose rubbing • manic condition can occur • drug wears off  severe depression or crash

  24. Side Effects and the Major Stimulants Common side effects • Stimulant (e.g., cocaine) psychosis • Euphoria, turns to paranoid delusion • With tactile & auditory hallucinations • Disrupted associative thinking • Commonly aggressiveness also found • Formication or parasitosis(bugs crawling all over or under skin) • occurs most commonly in repeat users

  25. Toxicity & Tolerance of Major Stimulants Toxicity • Related to peripheral actions on CV system • Heart attack or cerebral hemorrhage (stroke) • Severe depression  lead to suicide?? • May induce seizures with respiratory paralysis Tolerance • Decrease NT stores & receptor down regulation • Induces depression found in chronic users • Appetite suppression develops rapid tolerance along with CV actions

  26. Amphetamine Neurotoxicity • Amphetamine and methamphetamineare potentially neurotoxic • 10 to 50 times normal street dose (in rats; primates may be more sensitive) • Depletes DA and degenerates DA terminals

  27. Dependence & Major Stimulants Dependence • Moderate for occasional use via oral or intranasal route (e.g., Indians in Andes develop no dependence) • IV or smoking, severe dependence potential - want to have more to experience pleasure and ward off depression

  28. Other Stimulants

  29. Khat Cathinone • active agent in Khat (shrub) • chewed • synthetic version (meth-cathinone)

  30. Betel Nut • The fruit of the Areca catechu tree • Contains Arecoline • Mild stimulant that is a cholinergic agonist • Not a high abuse potential

  31. Ephedrine • from Ma Huang (herbal tea) • isolated in 1920’s • bronchodilator for asthma • pseudoephedrine is an isomer of ephedrine • structure similar to epinephrine