Embed Size (px)
Citation preview
Stimulants:Stimulants:Cocaine & AmphetamineCocaine & Amphetamine
Chapter 6Chapter 6
CocaineCocaine
Coke, Dust, Snow, Coke, Dust, Snow, Flake, Blow, GirlFlake, Blow, Girl
History of Cocaine History of Cocaine Dates back 5000 Dates back 5000
years in Peru & Boliviayears in Peru & Bolivia Coca leaves (2% Coca leaves (2%
cocaine) chewed by cocaine) chewed by IncasIncas
Mid to late 1850s, Mid to late 1850s, active ingredient of active ingredient of coca plant extracted coca plant extracted by Alfred Niemanby Alfred Nieman
History of CocaineHistory of CocainePopularized in 1880s Popularized in 1880s Sherlock Holmes (IV Sherlock Holmes (IV
cocaine user)cocaine user) Gave him energy & Gave him energy &
increased powers of increased powers of deductive reasoningdeductive reasoning
Sigmund FreudSigmund Freud advocated cocaine for advocated cocaine for
depression, indigestion, depression, indigestion, asthma, various asthma, various neuroses, drug addiction neuroses, drug addiction & local anesthetic& local anesthetic
History of CocaineHistory of Cocaine
Prescribed to morphine addicts & alcoholicsPrescribed to morphine addicts & alcoholics Available in patent medicinesAvailable in patent medicines Mariani's Coca Wine, mixture of red wine & Mariani's Coca Wine, mixture of red wine &
cocaine cocaine made by Angelo Marianimade by Angelo Mariani received gold medal from Pope (cited as benefactor of received gold medal from Pope (cited as benefactor of
humanity)humanity) In U.S. John Pemberton & French Wine Cola - In U.S. John Pemberton & French Wine Cola -
Ideal Nerve & Tonic Ideal Nerve & Tonic mixture of coca leaf & kola nut (caffeine)mixture of coca leaf & kola nut (caffeine)
Coca ColaCoca Cola
History of CocaineHistory of Cocaine In 1906, as many cocaine In 1906, as many cocaine
users in US as in ’76 with only users in US as in ’76 with only half the populationhalf the population
1906 Food and Drug Act 1906 Food and Drug Act Eliminated cocaine from Eliminated cocaine from
patent medicines & soft patent medicines & soft drinksdrinks
1903 Coca Cola 1903 Coca Cola decocainized Cokedecocainized Coke
Harrison Narcotic Act of 1914Harrison Narcotic Act of 1914 Further limited cocaine use Further limited cocaine use
& drove up prices& drove up prices
History of CocaineHistory of Cocaine
Use also declined in Use also declined in popularity because of popularity because of public sentiment against public sentiment against drugdrug
By 1930s, cocaine pretty By 1930s, cocaine pretty much disappeared, but much disappeared, but was replaced by was replaced by amphetamine.amphetamine.
By the late 1970s, coke By the late 1970s, coke began a comeback and began a comeback and use levels exploded use levels exploded around 1985….crackaround 1985….crack
Cocaine: FormsCocaine: Forms
Coca leaf – < 2% cocaineCoca leaf – < 2% cocaine Cocaine HCL – PowderCocaine HCL – Powder Freebase – PasteFreebase – Paste Crack – Rock cocaineCrack – Rock cocaine
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
• 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
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
““Ice” or “Crank”Ice” or “Crank”““Ice” or “Crank”Ice” or “Crank” Pure Pure dd--
methylamphetamine methylamphetamine HCLHCL can be smoked because of can be smoked because of
puritypurity Started in the West moved Started in the West moved
east over timeeast over time Labs all over Duplin Co.Labs all over Duplin Co. Very dangerous to Very dangerous to
synthesizesynthesize
Routes of AdministrationRoutes of Administration
OralOral amphetamine good absorptionamphetamine good absorption cocaine not well absorbed (In the Andes, cocaine not well absorbed (In the Andes,
mixed with ashes)mixed with ashes) Intranasally - decent route for cocaineIntranasally - decent route for cocaine
However, causes blood vessels to constrict, However, causes blood vessels to constrict, which limits absorption.which limits absorption.
intranasal works for amphetamine, but painfulintranasal works for amphetamine, but painful Intravenous - both very effective via this Intravenous - both very effective via this
routeroute
Duration of ActionDuration of Action
Duration of ActionDuration of Action Cocaine - oral onset in 2-3 min with peak in 15-20 Cocaine - oral onset in 2-3 min with peak in 15-20
minmin duration less than 1 hrduration less than 1 hr IV or smoked - onset in 10 sec & peak in IV or smoked - onset in 10 sec & peak in
5-10 min5-10 min Amphetamine - oral effects after 30 min & peak in Amphetamine - oral effects after 30 min & peak in
2-3 hrs2-3 hrs duration 10-12 hrsduration 10-12 hrs IV or smoked - onset 5 min & lasts up to 7 hrsIV or smoked - onset 5 min & lasts up to 7 hrs
Actions of cocaineActions of cocaineActions of cocaineActions of cocaine
Fowler et al. (2001)
Action of MethAction of MethAction of MethAction of Meth
Hours
Smoked vs. OralAmphetamine
Cocaine and NeurotransmissionCocaine and Neurotransmission Primary effect on DA Primary effect on DA
& NE with some 5HT & NE with some 5HT influenceinfluence Block reuptakeBlock reuptake Inhibit MAOInhibit MAO
Amphetamine and Amphetamine and NeurotransmissionNeurotransmission
Stimulates Stimulates release of DA release of DA and NEand NE
Blocks reuptake Blocks reuptake of DA and NEof DA and NE
Biotransformation & ExcretionBiotransformation & Excretion
Drugs have different routes of Drugs have different routes of biotransformationbiotransformation cocaine broken down in bloodstreamcocaine broken down in bloodstream amphetamine broken down in liveramphetamine broken down in liver
Both are excreted by the kidneysBoth are excreted by the kidneys
Physiological & Psychological Physiological & Psychological EffectsEffects
Cocaine & amphetamine indistinguishable Cocaine & amphetamine indistinguishable to IV usersto IV users
Oral or nasal route - local anesthetic Oral or nasal route - local anesthetic properties would set them apartproperties would set them apart
Effects on Nervous SystemEffects on Nervous System
Actions - wide variety Actions - wide variety of influences on PNS of influences on PNS & CNS& CNS Periphery - Periphery -
sympathomimeticssympathomimetics increase BP, HR, body increase BP, HR, body
temp, metabolic ratetemp, metabolic rate
Increase physical Increase physical strength & endurancestrength & endurance
Central Nervous SystemCentral Nervous System
Low or acute doses Low or acute doses increased arousal increased arousal
level & alertnesslevel & alertness improve performance improve performance
on simple taskson simple tasks produce mild euphoriaproduce mild euphoria increase of sex drive increase of sex drive
early on, but reverses early on, but reverses with prolong usewith prolong use
High Dose & CNSHigh Dose & CNS
Higher doses - (i.e., Higher doses - (i.e., smoking)smoking) intense feeling of euphoriaintense feeling of euphoria described as “whole body described as “whole body
orgasm”orgasm” hyperactivityhyperactivity repetitive behaviors - hand repetitive behaviors - hand
clasping, nose rubbingclasping, nose rubbing manic condition can occurmanic condition can occur drug wears off drug wears off severe severe
depression or crashdepression or crash
Side Effects and the Major Side Effects and the Major StimulantsStimulants
Common side effectsCommon side effects Stimulant (e.g., cocaine) psychosisStimulant (e.g., cocaine) psychosis Euphoria, turns to paranoid delusionEuphoria, turns to paranoid delusion
With tactile & auditory hallucinationsWith tactile & auditory hallucinations Disrupted associative thinkingDisrupted associative thinking Commonly aggressiveness also foundCommonly aggressiveness also found
Formication or parasitosisFormication or parasitosis (bugs crawling (bugs crawling all over or under skin)all over or under skin) occurs most commonly in repeat usersoccurs most commonly in repeat users
Toxicity & Tolerance of Major Toxicity & Tolerance of Major StimulantsStimulants
Toxicity Toxicity Related to peripheral actions on CV systemRelated to peripheral actions on CV system
Heart attack or cerebral hemorrhage (stroke)Heart attack or cerebral hemorrhage (stroke) Severe depression Severe depression lead to suicide?? lead to suicide?? May induce seizures with respiratory paralysisMay induce seizures with respiratory paralysis
ToleranceTolerance Decrease NT stores & receptor down regulationDecrease NT stores & receptor down regulation
Induces depression found in chronic usersInduces depression found in chronic users Appetite suppression develops rapid tolerance along Appetite suppression develops rapid tolerance along
with CV actionswith CV actions
Amphetamine NeurotoxicityAmphetamine NeurotoxicityAmphetamine NeurotoxicityAmphetamine Neurotoxicity
Amphetamine and Amphetamine and methamphetaminemethamphetamineare potentially are potentially neurotoxicneurotoxic 10 to 50 times normal 10 to 50 times normal
street dose (in rats; street dose (in rats; primates may be more primates may be more sensitive)sensitive)
Depletes DA and Depletes DA and degenerates DA degenerates DA terminalsterminals
Dependence & Major StimulantsDependence & Major Stimulants
DependenceDependence Moderate for occasional Moderate for occasional
use via oral or intranasal use via oral or intranasal route (e.g., Indians in route (e.g., Indians in Andes develop no Andes develop no dependence)dependence)
IV or smoking, severe IV or smoking, severe dependence potential - dependence potential - want to have more to want to have more to experience pleasure and experience pleasure and ward off depressionward off depression
Other StimulantsOther Stimulants
KhatKhatKhatKhat
CathinoneCathinone active agent in Khat (shrub)active agent in Khat (shrub) chewedchewed synthetic version (meth-cathinone)synthetic version (meth-cathinone)
CH NH2C
CH3
O
Cathinone
Betel NutBetel Nut
The fruit of the The fruit of the Areca catechu treeAreca catechu tree
Contains ArecolineContains Arecoline Mild stimulant that Mild stimulant that
is a cholinergic is a cholinergic agonistagonist
Not a high abuse Not a high abuse potentialpotential
EphedrineEphedrineEphedrineEphedrine
from Ma Huang (herbal tea)from Ma Huang (herbal tea) isolated in 1920’sisolated in 1920’s bronchodilator for asthmabronchodilator for asthma pseudoephedrine is an isomer of pseudoephedrine is an isomer of
ephedrineephedrine structure similar to epinephrinestructure similar to epinephrine
CH NHCH CH3
CH3
OH
Ephedrine
