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Caffeine

Caffeine. 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)

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Caffeine

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  1. Caffeine • 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!

  2. 200 mg in 4 ounces!!!! “

  3. A bit of history • 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

  4. 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

  5. Cutty Sark - renovated Tea- clipper last survivor - mid 1800’s now in Greenwich England called “Clipper ships” - very fast sailing ships built to cut the time needed to get tea from India and China back to Europe

  6. pharmacokinetics • 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

  7. Caffeine 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).

  8. metabolized by liver before excretion • main metabolites; theophylline, theobromine • CYP1A2 enzyme • certain SSRI antidepressants (flovoxamine) are potent CYP1A2 inhibitors – caution needed…..

  9. Caffeine Tolerance: Some effects that became tolerant in humans: • Blood pressure, heart rate • Adrenalin, noradrenalin levels • Anxiety, nervousness, energy

  10. Caffeine Tolerance: Some effects that did not show tolerance: • Caffeine-induced alertness and wakefulness • Cerebral energy metabolism

  11. 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

  12. Caffeine 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

  13. Caffeine and cognitive performance • 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…..

  14. What is too much caffeine? • 600-750mg a day of caffeine probably will NOT make someone feel very well

  15. Caffeine 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

  16. methylxanthines 3 types of related alkaloids from plants • theophylline • caffeine • theobromine

  17. methylxanthines share several pharmacological actions of therapeutic interest • relax smooth muscle (notably bronchial muscles) • stimulate CNS and cardiac muscle • theophylline and caffeine more than theobromine • produce diuresis in kidneys

  18. Uses of methylxanthines • 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

  19. psychostimulant effects • 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

  20. Not good for • anxiety disorders • tremors • possible dehydration

  21. Mechanism of action (CNS) • 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

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