most commonly consumed psychoactive drug in the world ◦ in us – consumed by 80% adult population...
TRANSCRIPT
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most commonly consumed psychoactive drug in the world◦ in US – consumed by 80% adult population◦ found in coffee, tea, cola, chocolate and cocoa◦ also found in many prescription and OTC
medications (FDA estimates ~1000 prescription and 2000 OTC
contain caffeine) safe and can be added to just about anything that we
can swallow!
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200 mg in 4 ounces!!!!
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commodity traded most extensively in the world is oil (wars fought over oil)
Next most widely traded commodity◦ caffeine
raw material includes coffee beans, tea leaves, cola nuts
estimates ~ 120,000 tons/year; employs more than 20,000,000 people
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Chinese claim to have discovered tea around 2700 BCE
At least ½ the world drinks tea England and China – fed each others
addictions◦ China provided tea for England and England (from
their British Colonies close to India) provided China with Opium
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Cutty Sark - renovated Tea- clipperlast survivor - mid 1800’snow in Greenwich England
called “Clipper ships” -very fast sailing ships built to cutthe time needed to get tea fromIndia and China back to Europe
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absorption – oral caffeine is rapidly and completely absorbed◦ significant blood levels within 30 – 45 min;
completely absorption over next 90 min◦ freely and equally distributed throughout the
body◦ crosses placenta to fetus
breast milk = or exceeds level in maternal plasma
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Pharmacokinetics: Half-life is ~3.5–5 hour in adult humans,
but 60–100 hours in infants.
Half-life is reduced by 30–50 percent in smokers; doubled in women on oral contraceptives (and prolonged during last trimester of pregnancy).
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metabolized by liver before excretion◦ main metabolites; theophylline, theobromine◦ CYP1A2 enzyme
certain SSRI antidepressants (flovoxamine) are potent CYP1A2 inhibitors – caution needed…..
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Tolerance:Some effects that became tolerant in humans:
◦ Blood pressure, heart rate◦ Adrenalin, noradrenalin levels◦ Anxiety, nervousness, energy
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Tolerance: Some effects that did not show tolerance:◦ Caffeine-induced alertness and wakefulness◦ Cerebral energy metabolism
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Sleep is the physiological function most sensitive to the effects of caffeine.
◦ Caffeine increases the time it takes to go to sleep and the total duration, but does not disturb the phases.
◦ Some tolerance develops to sleep disturbance.
EFFECT OF AN ADENOSINE ANTAGONIST (CAFFEINE) ON SLEEP IN A NORMAL SUBJECT
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Reinforcement: not a powerful reinforcer in animals self-
administering intravenously. Reinforcement varies with dose –
◦ does not directly increase DA in mesolimbic regions – maybe prefrontal cortex
Discrimination Human subjects can discriminate caffeine
from placebo, in coffee or capsules Doses of 300 mg or more are most reliably
detected, but some people can detect much lower doses
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ingestion of 85 – 250 mg caffeine (1 -3 cups of coffee) increases capacity for sustained attention and decreased reaction time
fine or delicate muscular coordination or timing…..
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600-750mg a day of caffeine probably will NOT make someone feel very well
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Toxicity: Caffeinism – (typically above 1000 mg/kg
6 deaths in humans; lethal dose estimated at 10 grams taken orally (about 100 cups of coffee); death is due to convulsions and respiratory collapse.
Is caffeine safe in pregnancy? ◦ Controversial
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3 types of related alkaloids from plants
1. theophylline2. caffeine3. theobromine
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1. relax smooth muscle (notably bronchial muscles)
2. stimulate CNS and cardiac muscle• theophylline and caffeine more than
theobromine
3. produce diuresis in kidneys
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therapeutically- used to treat a variety of disorders ◦ asthma (theophylline mostly to relax
respiratory muscles)◦ narcolepsy (to maintain daytime wakefulness)◦ migraine◦ adjunct to treat headache and other pain
syndromes
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Caffeine – effective psychostimulant
heavy consumption (12 or more cups/day or 1.5 g caffeine)◦ agitation, anxiety, tremors, rapid breathing,
insomnia lethal dose – 10 g (100 cups of coffee) people with anxiety disorders – especially
sensitive to caffeine
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anxiety disorders tremors possible dehydration
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caffeine exerts variety of effects in CNS at different doses◦ most likely – blockade of adenosine receptors ◦ so adenosine antagonist!◦ represents major site of action
Adenosine –◦ neuromodulator of several nt in CNS◦ majority of adenosine effects are sedating,
depressing, and anticonvulsant