Transcript Drugs

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the federal drug policy under which the
manufacture, importation, possession, use
and distribution of certain substances is
regulated
Categorized certain drugs into 5 classes
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high addictive potential – not considered of
medicinal value
There is a lack of accepted safety for use of
the drug or other substance under medical
supervision
No prescriptions may be written for Schedule
I substances, and such substances are subject
to production quotas by the DEA.
◦ mescaline, lysergic acid diethylamide, heroin, and
marijuana, gamma hydroxy butyrate (GHB),
ibogaine
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Drugs with a high abuse risk, but also have
safe and accepted medicinal uses
Abuse of the drug or other substances may
lead to severe psychological or physical
dependence
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stimulants, opiates, methadone, codeine,
methylphenidate (Ritalin), mixed salt amphetamine
(Adderall),
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less abuse potential than Schedule I or II
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has a currently accepted medical use in
treatment in the United States.
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abuse of the drug may lead to moderate or
low physical dependence or high
psychological dependence.“
◦ – includes barbiturates, anabolic steroids, ketamine
(?), buprenorphine, marinol (synthetic THC)
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medical use, less abuse liablity, less risk of
physical dependence
◦ benzodiazepenes (?) – although n of prescriptions is
controlled
◦ some barbiturates
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Schedule V
◦ cough suppressants with small amounts of codeine
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History
◦ Cocaine
◦ Source: leaves of E. coca (indigenous to western
South America
◦ word spread through explorers, naturalists, botanists
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History
◦ Cocaine
◦ Source: leaves of E. coca (indigenous to western
South America
◦ word spread through explorers, naturalists, botanists
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1860’s – a variety of medicinal uses
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History
◦ Cocaine
◦ Source: leaves of E. coca (indigenous to western
South America
◦ word spread through explorers, naturalists, botanists
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1860’s – wine tonics
Launched in 1863- European
success; the world's most popular
prescription
Some of its advocates; Henrik Ibsen,
Jules Verne, Alexander Dumas, Robert
Louis Stephenson, Sir Arthur Conan Doyle,
Queen Victoria; King George 1 of Greece;
King Alphonse XIII of Spain; the Shah of
Persia; William McKinley, President of the
United States.
Sears and Roebuck,
1900
"...sustains and
refreshes both the
body and brain....It
may be taken at any
time with perfect
safety...
it has been
effectually proven
that in the same
space of time more
than
double the amount of work could be
undergone when Peruvian Wine of Coca
was used, and positively no fatigue
experienced....."
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History
◦ Cocaine
◦ Source: leaves of E. coca (indigenous to western
South America
◦ word spread through explorers, naturalists, botanists
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1860’s – wine tonics
1884 - Freud
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as a mental stimulant
as a possible treatment for digestive
disorders
as an appetite stimulant in case of
wasting diseases
as a treatment for morphine and
alcohol addiction
as a treatment for asthma
as an aphrodisiac
as a local anaesthetic
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mid 1880’s –
◦ Atlanta druggist John
Pemberton – devised a patent
medicine that contained two
naturally occurring stimulants;
cocaine and caffeine
 Coca-cola – advertised as an
intellectual beverage
 a temperance drink; a brain tonic
 Pemberton sold 2/3 of his interest
in 1887 for $283.29
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late 1800’s until 1903
◦ Coca Cola had ~ 60 mg/ 8 ounces
◦ 1903 Coca Cola stopped having cocaine
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1914 – Harrison Narcotic Act –
◦ listed cocaine as a narcotic
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synthesized in the lab (in early 1900’s)
first marketed in 1927
drug has been abused since its introduction
benzedrine inhalers used by a wide
segment of population during 1930’s
amphetamines and war
amphetamines and weight reduction
◦ 1967 – estimates of 23,000,000 prescriptions in
US for weight reduction
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Cocaine use still rose during the 1920’s
but then decreased in 1930’s because
amphetamines became available (and at
the time cost less, were more easily
available AND the euphoria lasted longer)
Amphetamine took over in popularity
during the 1940’s – 1960’s. In 1970’s
restrictions on amphetamine tightened
◦ made amphetamine a schedule II drug so….
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some estimate 1.8 million Americans users of
cocaine in 1998; majority between 18 and 34
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males more likely than females
males more likely to use higher amount
males more likely to use for longer duration
significant proportion met criteria for ADHD
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coca leaves
◦ leaves can be soaked and mashed to form coca
paste
 oral – 70 – 80% broken down by liver biotransformation
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cocaine hydrochloride
coca paste treated to form salt
water soluble and can be taken intranasally or injected IV
snorting – not very efficient because cocaine
hydrochloride is ionized; also cocaine has
vasoconstrictive properties (so it limits its own
passage into blood vessels)
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IV – onset is rush ~ 30 – 45 secs
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freebase- extracted from crystalline from with
either ether or sodium hydroxide
◦ duration lasts 10 – 20 min;
◦ 100% reaches circulatory system
◦ vaporized at lower temps than cocaine hydrochloride and
so can be inhaled
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crack – freebase but extracted with alkaline water
and premade (or prepackaged)
smoking not really efficient for delivering cocaine
to body because significant portion is lost to
pyrolysis – but remaining dose produces intense
effect
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originally regional specificity
spreading across nation (ease of production
although dangerous- explosions, toxic
substances, etc)
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illicit amphetamine production estimated
to be in the billions/year
methamphetamine
◦ made in growing numbers of clandestine labs
◦ produces greater cortical stimulation than some
other amphetamines
◦ huge profit margin
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ice – free base form of amphetamine
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Estimated that for each pound of
methamphetamine produced, between five
and six pounds of highly toxic waste is
generated.
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amphetamine
◦ causes release of newly synthesized monoamines
◦ also blocks reuptake of monoamines
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cocaine
◦ blocks reuptake of monoamines
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stereotypic behavior
◦ high doses result in stereotyped behaviors
representative for respective species
 in rat, can be sniffing, licking, biting or gnawing
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Appetite suppression
◦ weight loss
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Aggression
◦ several descriptions of murder and other violent
offenses attributed to amphetamine intoxication
cardiovascular
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heart disease
increased risk for CVA
cardiac arrhythmia
increased blood pressure
respiratory
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chest pain
respiratory complications
difficulty breathing
neurotoxic
◦ seizures
intracranial hemorrhages
◦ cocaine or amphetamine induced psychosis
◦ formication
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methylphenidate (Ritalin)
◦ causes release of newly synthesized DA
◦ also blocks reuptake of DA
“Adderall”
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Strattera –atomexetine HCl
◦ first non stimulant pharmacotherapy for ADHD
◦ blocks reuptake of NE instead of DA
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methylated amphetamine –
text covers this in chapter with hallucinogens
(affects 5HT as well)
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UNTIL RECENTLY - sold in health food stores and
on internet
Now – no longer on US market!
◦ ephedra – also known as ma huang; herb
◦ FDA received many reports from doctors, government
health authorities and others about adverse-based
ephedrine based products
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Currently – OTC subject to FDA regulations
HOWEVER herbal supplements currently are
essentially unregulated – may soon change!
◦ either decreased effectiveness or potency of a drug
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How does tolerance occur?
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Data is mixed
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acute tolerance
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acute tolerance
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animal models –
◦ sensitization
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Psychological dependence – very strong!
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Physical dependence – WD?
◦ Cocaine crash
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operant performance
animals will self administer in absence of
tolerance, physical dependence, withdrawal
or prior drug taking history
two bar test
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variation in extent and rate of self
administration depends on drug being
administered
ex. opiates – uniform and constant
administration (moderate and measured
with voluntary abstinence)
cocaine – frenzied intake followed by
abstinence
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enhances basal neuronal firing or basal NT
release in “reward circuit”
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dose-response rates at fixed ratios
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progressive ratio schedule
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how hard is the animal willing to work for drug
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drug discrimination –
◦ 2 bar discrimination
◦ what does this tell us?
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initially trained to self administer drugs
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followed by extinction
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priming or nondrug stimuli
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good predictive validity - reinstate heroin and
cocaine seeking in laboratory animals
including as drug reexposure, drug cues, and
stress (Self and Nestler, 1998; Shaham et al.,
2000a; Stewart, 2000)
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non specific drug effects
only test the rewarding component of drug
during “intoxicated” state
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rewarding stimulus is repeatedly paired with
neutral environmental stimulus
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food, water, brain stimulation, sexual partner
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drugs
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can study reinforcing effects of a drug in
drug free state
can sometimes see CPP in one trial
(IV particularly)
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Animals find amphetamine and cocaine highly
rewarding