Lesson 9 chapter 6: Cocaine and amphetamines (lesson + textbook notes) PDF

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Instructor for this course was Bruce McKay. Course was remote and online....

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Lesson 9: Cocaine and Amphetamines Lesson Objectives 1. Describe the early history of cocaine purification and psychiatric use 2. Compare and contrast the various forms of cocaine 3. Describe the acute and chronic toxicity associated with cocaine use 4. Describe the production of methamphetamine in general terms pointing out the risks inherent to the use of specific reagents 5. Describe medical uses of amphetamines including the treatment of ADHD 6. Discuss the potential role for amphetamines in cognitive enhancement

Lesson Review Questions 1. Describe the early history of cocaine and its ‘medicinal’ and ‘psychiatric’ uses. Name some of the key figures in the history of cocaine. 2. Where is the coca plant grown? 3. What is the difference between cocaine and crack cocaine? (acute and chronic effects, route of administration, dependence potential, etc) 4. What are amphetamines? How are they similar to the classical neurotransmitters? 5. What are the acute and chronic effects of amphetamines? 6. What is methamphetamine? 7. What are some modern ‘medical’ uses of amphetamines? 8. Discuss the role of putative amphetamines as cognitive enhancers.

Lesson Notes • • • • • •

Textbook Chapter 6: Stimulants Textbook Objectives 1. Discuss the history of cocaine and amphetamines 2. Describe early psychiatric uses of cocaine 3. Describe how cocaine hydrochloride and crack cocaine are processed from coca 4. Compare and contrast the illicit supply sources for cocaine and methamphetamine in Canada

5. Compare and contrast the illicit supply sources for cocaine and methamphetamine in Canada 6. Compare and contrast the mechanism of action and route of administration of cocaine and amphetamines 7. Compare and contrast acute and chronic toxicity concerns associated with cocaine and amphetamines 8. Compare the chemical structure of amphetamine to the catecholamine neurotransmitters and to ephedrine

Textbook Review Questions 1. At about what periods in history did cocaine reach its first and second peaks of popularity, and when was amphetamine’s popularity at its highest? 2. How did Mariani, Freud, and Koller popularize the use of cocaine? 3. How are coca paste, freebase, crack, and ice similar? 4. What similarities and what differences are there in the toxic effects of cocaine and amphetamine? 5. Contrast the typical “speed freak” of the 1960s with the typical cocaine user of the early 1980s and with our stereotype of the modern crack smoker 6. How does the chemical difference between methamphetamine and amphetamine relate to the behavioural effects of the two drugs? 7. Compare the dependence potential of cocaine with that of amphetamine

Textbook Notes Cocaine • History ㄴ Andes Mountains • Coca Wine ㄴ 1850-1880s - Angelo Mariani • Local Anaesthesia ㄴ 1884 - Karl Koller • Early psychiatric Uses ㄴ Freud liked it, then rebutted it ㄴ 1885, The Park-Davis Pharmaceutical Company • Legal Controls on Cocaine ㄴ 1974 Peter Bourne advocated use of Cocaine ㄴ Mid-late 1980s crack cocaine (smokeable) became available ㄴ Cocaine is a schedule I drug, $1000 fine or imprisonment-life in prison

• Supplies of Illicit Cocaine in Canada ㄴ Major suppliers, Colombia, Peru, Bolivia ㄴ Production control is difficult ㄴ U.S. biggest transit company, Mexico is close • Pharmacology of Cocaine ㄴ Leaves contain up to 2% cocaine ㄴ Chemical Structure: not much • mind/body connection: Cocaine • Forms of Cocaine ㄴ Coca leaves are mixed with kerosene or gasoline, turns into coca paste ㄴ Paste is made into cocaine hydrochloride ㄴ Powder form, unsmokable but mixes in water ㄴ Can be turned into freebase to smoke using ether (explosive) ㄴ Can be turned into crack using baking soda + water • Mechanism of Action ㄴ Blocks reuptake of dopamine, norepinephrine, serotonin (makes these last longer in the synapse) ㄴ Binds to dopamine transporter, blocking it and creating a dopamine buildup ㄴ =Euphoria ㄴ Latest: dopamine, serotonin, GABA, and glutamate are all involved • Absorption and Elimination ㄴ Chewing leaves = slow effect, lower blood levels ㄴ Snorting cocaine hydrochloride (onto nasal mucosa) = rapid ㄴ Intravenous = high concentration to the brain, rapid and brief effects ㄴ Less popular than crack ㄴ Metabolized in blood & liver by enzymes, differs from person to person ㄴ Cocaine molecules = 30 min half life ㄴ Major metabolites (urine screening) = 8h half life • Medical uses of Cocaine ㄴ Local Anaesthesia ㄴ 1860, numbness effect discovered ㄴ 1884 used medically in eye surgery/dentistry ㄴ 1905, procaine ㄴ Cocaine still used for nasal, laryngeal, and esophageal regions ㄴ Other Claimed Benefits

ㄴ Stops fatigue (CNS) ㄴ CNS effect has not been used due to dependence risk • Causes for concern ㄴ Occasional small amounts are ok, but dependence is high ㄴ Acute Toxicity ㄴ CNS stimulation, convulsions, respiratory/cardiac arrest ㄴ Individual variability means lethal dose is hard to know ㄴ Cocaine and alcohol can result in cocaethylene which is more toxic than cocaine ㄴ Chronic Toxicity ㄴ Runny nose ㄴ Cocaine binging = irritability, restlessness and paranoia ㄴ Severe cases, paranoid psychosis ㄴ Potential heart muscle damage ㄴ Dependence Potential ㄴ Largest admissions for drug treatment ㄴ Cocaine is a powerfully reinforcing drug ㄴ Abuse potential is not defined by physical withdrawal signs (cocaine was not considered addictive, it is now) ㄴ Withdrawal symptoms: ㄴ Cocaine craving, irritability, anxiety, depression, large appetite, exhaustion. ㄴ Severity depends on dosage, purity, frequency, chronicity of use, route of administration, other drug use, and medical/psychiatric complications ㄴ Reproductive Effects ㄴ “Crack baby”, number and long term effects overstated, No consistent negative associations ㄴ Still not recommended due to miscarriage and torn placenta ㄴ Alcohol still worse • Current patterns of Cocaine Use ㄴ Worldwide annual: 15.6-20.8 million (2007) ㄴ Low use in Canada • Cocaine’s Future ㄴ Cocaine and amphetamines balance each other (one goes down, the other goes up) ㄴ History repeats...

ㄴ 1st stage (1880s) - positive opinions ㄴ 2nd stage (1890s) - more use, dangers more well known ㄴ 3rd stage (e1900s) - society turns, laws are made

Amphetamines • History ㄴ Chinese medicinal tea from herbs (ma huang/Ephedra) ㄴ Ephedrine - active ingredient, sympathomimetic ㄴ All major effects discovered in 1930s ㄴ Replaced ephedrine in asthma treatment ㄴ 1935, treatment for narcolepsy, but ended with 2 patients developing psychotic reactions in 1938 ㄴ 1937, reduced hyperactivity in children and students used it to cram ㄴ 1939, no hunger • Wartime Uses ㄴ Air surgeon’s bulletin report “Benzedrine Alert” advocated its wakefulness effects ㄴ Germany, Canadian, US and Japanese were given amphetamines ㄴ Stockpile of amphetamines lowered their price, government sold it cheap • The “speed scene” of the 1960s ㄴ 1920s-1930s, intravenous introduced, heroin and cocaine together became known as speedball ㄴ Amphetamines replaced cocaine in the mixture, AKA “speed” ㄴ Use peaked in 1950s-1970s with legal oral preparations ㄴ 1960s “fat doctors”, treated obesity with amphetamines ㄴ “Flower children” mixed with bad drug culture, drew national concern ㄴ Went from widely accepted to restricted ㄴ Results of restrictions ㄴ “Look-alike” pills: legal, milder stimulants (caffeine, ephedrine) that looked like amphetamines ㄴ 1970s, Price=up & quality=down, cocaine became popular • The return of methamphetamine ㄴ Results of restrictions cont’d ㄴ Illicit labs made methamphetamines (crank) ㄴ 1989, smoking of methamphetamine hydrochloride crystals (Ice/Crystal meth) was the new drug epidemic

ㄴ Became a club drug ㄴ Single time use doubled from 1990 (4milllion)-1999 (9 million) • Drugs in depth: looking at meth addiction • Supplies of illicit methamphetamine in Canada ㄴ Certain lifestyles are attributed to demand for amphetamines ㄴ $80-$150, but can go as low as $50 in Vancouver ㄴ Quebec prefers tablets ㄴ Canada is a source country, pushed to make 3 regulations: ㄴ 1st & 2nd on precursor chemicals ㄴ 3rd on essential chemicals ㄴ Affected producers of lower-quality methamphetamines • Pharmacology of Amphetamines ㄴ Source ㄴ Chemical synthesis in companies or illicit street labs ㄴ Chemical structure ㄴ Amphetamine molecule’s shape is similar to that of dopamine and norepinephrine ㄴ Has “left-handed” & “right-handed” forms (l and d forms) ○ D form is more potent in CNS effects ○ 1945 d-amphetamine/dexedrine used as appetite suppressant ㄴ Methamphetamine molecule = addition of methyl structure ㄴ Helps pass through the blood brain barrier, increases CNS potency ○ This doesn’t actually make behaviour any different ㄴ Ephedrine and phenylpropanolamine (PPA) do not cross the blood brain barrier very well = less CNS stimulation • Mechanism of action ㄴ Increase the release of dopamine, norepinephrine, and serotonin, and block their reuptake ㄴ While cocaine works on all 3 monoamine transporters, amphetamines mostly impact norepinephrine (5-9x more on norepinephrine than on dopamine, no effect on serotonin • Absorption and elimination ㄴ Bioavailability: ㄴ Intravenous - 100% ㄴ Inhalation - 90%

ㄴ Oral - 67% ㄴ Intranasal - 79% ㄴ Complete elimination within 2 days ㄴ Tachyphlaxis = rapid tolerance, Reduces available monoamine transmitters, so large doses they may be depleted • Medical uses of amphetamines ㄴ 1970s FDA restricted amphetamines to narcolepsy, hyperactivity, and short-term weight loss ㄴ Previous use for depression ㄴ 1950s-1960s ㄴ Drug boosts mood, then drops it below pre drug levels ㄴ Weight control ㄴ Mid 1960s ㄴ Effect is real, but small and limited in duration, 4-6 weeks before tolerance ㄴ Meridia (sibutramine) was used as a substitute from 1997-2010, showed high risk for cardiovascular problems ㄴ Narcolepsy ㄴ Modafinil (Alertec) promotes wakefulness and has a low abuse potential ㄴ Hyperactive Children ㄴ Methylphenidate (Ritalin) has many side effects ㄴ Atomoxetine (Strattera) is good, and does not have abuse potential ㄴ Amphetamines may help sometimes, but it's a risk because it might just make you too excited to concentrate ㄴ Athletics ㄴ 1% increase, but it's enough to move from 6th to 1st • “Smart Pills” ㄴ Cylert started as a “smart pill”, now used as an ADHD alternative • Causes for Concern ㄴ Acute toxicity ㄴ Complex decisions impaired ㄴ Contaminants formed in production destroy brain cells ㄴ High doses: ㄴ Aggression due to: Panic, paranoia, as well as feelings of power/capability

ㄴ Violence: Drug doesn’t hurt so much as what you do ON the drug does ㄴ Chronic toxicity ㄴ Paranoid psychosis is from the drug, not the user ㄴ Lasts for a while (days or weeks), but so far is not permanent ㄴ Compulsive and repetitive actions (effect on dopaminergic systems in the basal ganglia) ㄴ Dependence Potential ㄴ Parallel to cocaine: craving, lethargy, depressed mood etc. ㄴ Dose and route of administration, as well as intent, play a major role...