Exam 2

South America- Peru, Bolivia, Columbia

Cocaine is derived from coca leaves grown in the mountains of?

Orally administered, chew the leaves, 2-5% pure

Coca Leaf form

smokeable, moderate concentration, 60% pure, not water soluble

Coca Paste (basuco), Cocaine sulfate

intranasal or injection routes, 99% pure, water soluble

Street cocaine, Cocaine hydrochloride

smokeable, 75% pure, cheaper version

Crack

smoked, 75% pure, more expensive version

Free base

held important religious significance to Incas, was also used for medicinal purposes and work for energetic highs

Indiginous peoples of South america used coca leaves for?

1880s, 19th century epidemic in Europe and United States

Second era of cocaine use

a German who isolated and named Cocaine

Alfred Niemann

purified it and put it in wine, alcohol + cocaine= longer half life, (cocaethylene)

Angelo Mariani

helped launch harmful period of cocaine use and used it freguently himself

Sigmund Freud

first diagnosed with formication syndrome

Von Fleischel-Marxow

one hallucinates the feeling of insects crawling all over them

formication syndrome

used it as a local anesthetic for eye surgery

Karl Koller

made Coca Cola

Pamberton

used cocaine to anesthetie nerves

William Halstead

1900-1915

Peak cocaine use?

Harrison Narcotic Act of 1914

tax law to regulate sales of cocaine

1980s, 20th century epidemic in US

Third era of cocaine use?

sniffing low intranasal doses, low rate of major problems

early 1970s

Freebase, cocaine mixed with highly flammable ether and was expensive, Glamour Drug

late 1970s

Crack, made cheaper and caused widespread use causing an national crisis in 1986

1980s

3.5

cocaine use 18-25

0.2

heroine use 18-25

cocaine + heroin

speedball

efficacy is reduced, is a weak base so ionization occurs in stomach and takes 10-15 min for drug action to begin

oral administration of Cocaine

good absorption, BIG CNS stimulation for 15-30 min then crash, snorting 20-30mg = ~ 1 line

Intranasal administration of Cocaine

LARGE doses introduced very quickly ~16mg, drug hits within seconds and causes a state of euphoria but lasts only 5-10 min, BIG crash so they re administer every 10-30 min

IV Injection of cocaine

effects are as intense and faster than IV Route

Inhalation of cocaine

fast, effects last from 20-80 min

Cocaine is etabolized ………

fast, 40 min half life

cocaine is excreted……….

possible for a significant percentage of sudden unexplained deaths in cocain users

cocaethylene toxicity

acts as local anesthetic

effects of cocaine on the somatic nervous system

acts as a sypathomimetic (increases sympathetic activation)

effectd of cocaine on the autonomic nervous system

blocks reuptake, especially of DA synapses, nucleus accumbens

Cocaine effects on the CNS

a powerful burst of energy and sense of well-being, decreased appetite, high doses can cause delusions and paranoia, sudden death, cardiac arrest and cerebral hemorrage

accute effects of cocaine

depression, anxiety, decreased sexualperformance, cocaine psychosis, deterioration of nasal membranes, reduce dopamine receptors in brain by 20%

chronic effets of Cocaine use

to euphoric effects

acute tolerance of cocaine

appetite suppressing effects, heart and bp effects, lethal effects

functional tolerance of cocaine

no severe life threatening abstinence syndrome, depression, lack of energy, poor appetite, restlessness, and agitation

physical dependence and Withdrawl of cocaine

cravings

psycological dependence of cocaine

rats self administering drugs and cocaine was the MOST reinforcing drug

Pickens and Thompson (1968) study

a chinese herb used as a brinchial dilator, used by Shen Nung

Ma Huang

19th century, in Germany this ingredient was isolated from the plant (Ma Huang)

Ephredine

synthetic ephedra, first synthesized in 1887, good as an anti-asthmatic

Amphetamine

contained 250mg Benzedrine, used chiefly for asthma, people began to oversuse and abuse them

first inhaler 1932 (amphetamines)

marketed for narcolepsy

1935 first tablet form (Amphetamines)

used as treatment for depression and 37 other disorders

1937 AMA (Amphetamines)

used to help hyper active kids

1937 Charles Bradley (Amphetamines)

used during WW2 to ward off fatigue (oral administration)

1940s (amphetamines)

harmful use reaches epidemic levels in Japan, Sweden, and other parts of Europe, Not officially recognised as a danger in the US until 1960s

1950s (amphetamines)

physicians tried prescribing it to treat heroin dependence but backfired and users began injecting it, PEAK use was 1967-1970s

1960s (amphetamines)

inject every 2 hours for 3-6 days, sleep for 3 days, normal 3 days (eat a lot), repeat

typicla injection routine of amphrtamines

decline of amphetamine use

1970s (amphetamine)

Abuse of Methamphetamine (Crank), crystal meth

abuse of ephedra/ephedrine

increase in methylphenidate (Ritalin)

1990s (amphetamine)

appeared in the 1970s and reappeared in the early 1990s, street names: ice, crank, meth, crystal. today its known as a club drug and is estimated that 80% of meth in the US is made in Mexican labs

Methanphetamine

5-15mg, weak base so ionized in stomach, 30 min behavioral effects

oral administration (amphetamine)

LARGE dose very quickly, within second causeing a rush, normally taken with a barbiturate or heroin to take the edge off

IV administration (Amphetaines)

oral, intranasak, IV or inhalation

methamphetamine administration routes

metabolized by liver, half life 10-12 hours so a longer lasting high (4-12hrs) compared to cocaine (20-80min)

Distribution, metanolism and Excretion of amphetamines

norepinephrine and dopamine

amphetamines are similar in structure to

enhances release if neurotransmitters from axon, blocks reuptake of NE and DA, ay high doses it inhibits MAO

effects of amphetamines on CNS

sympathomimetic

effects of amphetamines in PNS

a general arousing agent (Insomnia, stereotyped behavior, attention/vigilance), antidepressant, anorectic, sympathomimetic (increased bp, sweating, heart rate, vasodilation, bronchodilation, tremors, increased body temp)

acute effects, low dose of amphetamines

acute effects, low dose of amphetamines

psychotic reactions (formication syndrome, punding, paranois), neurotoxicity (reduced DATs in striatum of meth user, can lead to early PD)

acute effects, high dose of amphetamines

develops to euphoric effects, but NOT to bp and heart rate (VERY dangerous)

acute tolerance of amphetamines

appetite suppresing effects, heart and bp effects, lethal effects

functional tolerance of amphetamines

depression, anxiety, changes in appetite, sleep disturbances, anhedonia (depletion of monoamines), hoghest relapse rate of all drugs

physical dependence and withdrawl of amphetamines

cravings VERY STRONG, taps into reward circuit

psycological dependence of amphetamines

narcolepsy, short-term weight reduction, short-term relief for nasal congestion, ADHD

amphetamines theraputic uses

Nicotiana tobacum- larg leaf form, modern tobacco originated from South America

Nicotiana rustica-small leaf form, native to eastern N. America

two major species of tobacco plants

nicotine, Tar, Carbon monoxide

whats in tobacco?

primary psychoactive ingredient in tobacco, acute pharmacologcial effects of smoking , the dependence on cigaretted, 60 mg can kill you

Nicotine

gives tobacco its taste and smell, is carcinogenic (affects ciliary scalator)

Tar

impedes the oxygen carrying capacity of the blood, impairs circulation, increases cholesterol deposites and arteriosclerosis

carbon monoxide

Southeast Asia and the Balkan region of Europe

highest smoking rates are found in?

11.5

cigarette use 18-25

14.1

vaping use 18-25

cigarette smoking

most common way to use tobacco?

Surgeon Generals 1964 report that detailed the hazards of smoking

decresed use of tobacco is likely linked to?

natives of South America

first to domesticate tobacco plant

discovered tobacco when saw native americans smoking dried tobacco leaves, learned of “tobacco drinking”

Christopher Columbus

introduced tobacco to Europe in 1559, people believed tobacco had medicinal properties up through 1860s

Jean Nicot

established trade with China, Brazil, India, Africa and Arabia, spreading it all over the world

Portuguese Sailors

snorting ‘snuff’ became popular in Europe, it was incredibly popular many tried to stop it but kept using it anyways.

early 17th Century (tobacco)

1828 french scientists isolatied nicotine as the active ingredient in tobacco, by 1860 medical use of tobacco had virtually ended

19th century (tobacco)

created the american tobacco industry

John Rolfe

traded tobacco for money to fund revolutionary war, chewing tobacco was adopted with patriotic ferver

George Washington & Ben Franklin

smoking cigars was popular, cigarette machine was developed

mid 19th century (tobacco)

future favored cigarettes so in 1920s-1940s they were highly sold, very chic to smoke and targeted young men

20th century (tobacco)

Peak use of tobacco in USA

1964 (Tobacco)

42.4% in 1965 - ~17% in 2017,

since 1964 (tobacco)

minimum age to purchase tobacco from 18 to 21

December 2019

most rapid and efficient method, the added ammonia causes faster absorption, enters lungs on tar particles

inhalation of nicotine

reached brain in 7 seconds

distribution of nicotine inhalation

reaches brain in 14 seconds

distribution of nicotine IV

about 70-80% od nicotine is transformed into cotinine by a liver enzyme (cytochromeP450 2A6), half life of 2 hours, eliminated in Urine (but also sweat, saliva and mothers milk)

metanolism and elimination of nicotine

CYP2A6, if you have less of this you tend to NOT be a smoker

genetic varieation in activity of?

is being tested for smoking cessation treatment

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