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CAFFEINE. The most widely consumed psychoactive substance in the world. Caffeine Basics. CNS stimulant Alkaloid from a chemical group called Xanthines Found in 63 species of plants Everyday 90% of Americans consume caffeine in some form. Methylxanthines.

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  1. CAFFEINE The most widely consumed psychoactive substance in the world.

  2. Caffeine Basics • CNS stimulant • Alkaloid from a chemical group called Xanthines • Found in 63 species of plants • Everyday 90% of Americans consume caffeine in some form

  3. Methylxanthines • Caffeine (1, 3, 7-trimethylxanthine) – found in coffee, sodas and some OTC medicine • Theophylline (1, 5-dimethylxanthine) – found in tea • Theobromine (3, 7-dimethylxanthine) – found in chocolate

  4. History • Plants evolve caffeine to protect themselves from attack by bacteria, fungi and insects. • 1st use of caffeine as early as 600,000 BCE • First historical record of caffeine use from Aztec records. • Homer makes reference to a mysterious black bitter beverage with the power to ward off sleep.

  5. History (cont.) 1475 - The worlds first coffee shop opens in Constantinople 1821 - Pure caffeine extracted from coffee 1880's - Caffeinated soft drinks appear 1903 - Researchers remove caffeine from beans ‘without destroying the flavor’ 1923 - Decaffeinated coffee is introduced to the United States

  6. More History 1940 - The US imports 70 percent of the world coffee crop. 1962 - American per-capita coffee consumption peaks at more than three cups a day. 1971 - First Starbucks opens in Seattle. 1995 - Coffee becomes the worlds most popular beverage (overtaking tea).

  7. Generation Wired • ‘Tweenagers’ consisting of 8 to 14 year olds are heavily targeted by marketers • Why do so many young tweenagers drink caffeinated beverages? • Coffee bars are often the only place for young people to hang out • Marketing of ‘cold-sweet’ coffee drinks and high caffeine sports/energy drinks

  8. Case of Mountain Dew • In Canada, adding caffeine to citrus drinks has not been allowed. The company that produces Mountain Dew has been fighting to add caffeine to Canadian Mountain Dew claiming to improve taste. • The Do the Dew ad campaign shows frenzied lifestyle

  9. Caffeine Contents 7-Up 0 mg Root Beer (non-Barq’s) 0 mg Tea, the elegant option 30-60 mg Coke 45.6 mg Mountain Dew 55 mg JOLT 71.2 mg of caffeine Coffee 80-135 mg Excedrin 130 mg per tablet No Doz 200 mg a pill In 1998 Americans guzzled 15 billion gallons of sodas, the equivalent of 585 cans for every man woman and child in America.

  10. Profiting Schools • Soda companies pay school districts for exclusive selling rights (Coke vs Pepsi) and for the right to put ads on the gym walls and school buses • 1997 in West Virginia a state law prohibiting the sale of soda in schools was overturned after extensive lobbying by soft-drink companies

  11. mixture of energy drinks and alcohol sold as expensive cocktails in many clubs 100mg of caffeine -- often sold without labels Dangerous when combined with alcohol High-Energy Cocktails

  12. Anheuser-Busch’s ‘BE’ Takes Beer to a New Level   ST. LOUIS (Oct. 4, 2004) – B-to-the-E (BE), Budweiser's newest entry in a long line of innovative beers by Anheuser-Busch, is a distinctive new product for contemporary adults who are looking for the latest beverage to keep up with their highly social and fast-paced lifestyles. 54 mg of caffeine (plus guarana and ginseng)

  13. Absorption through: Stomach Small intestine Large intestine Effects of caffeine Depends on: Food in the body Caffeine in the substance Pharmacokinetics: Route of Administration/Absorption

  14. Throughout the body and the brain Water soluble Crosses blood brain barrier Reaches the fetus No accumulation within body Distribution

  15. More Pharmacokinetics Dose: 100 mg = 1 Cup of Arabica Coffee (8oz) Route: Taken Orally Onset: 30-60 Minutes Peak At: 2 Hours Half-life: Approximately 3-7 hours

  16. Metabolism The enzyme CYP1A2 is responsible for the metabolism of caffeine in the liver. One form of the enzyme, produced by the gene variant 1A, metabolizes caffeine rapidly while another form, 1F, metabolizes it slowly. • Longer/Slower • Metabolism if: • Alcohol • Asians • Men • Newborn • Liver Damage • Pregnant • Shorter/Faster Metabolism if: • Cigarettes • Caucasians • Women • Child

  17. Metabolism • Smoking Will Metabolize Twice as Fast • Alcohol Will Metabolize Slowly

  18. Metabolism & Excretion • Metabolized by liver (first-order kinetics) • Excreted by kidney via urine (diuretic)

  19. Pharmacodynamics • Main mechanism of action: direct competitive antagonist of adenosine receptors - A1 and A2a • Effects on Monoamines: -Elevates levels of 5-HT in the brain -Stimulates NE neurons -Increases rate of DA formation →However, this may be quickly followed by a decrease →Yet, injection of caffeine usually increases locomotor activity, an effect supposedly blocked by a DA receptor antagonist

  20. Mechanisms of Action • Multiple mechanisms • Adenosine antagonist • - both A1 and A2 sites • 2nd messenger theory • - Phosphodiesterase inhibition • - cAMP, AMP, intracellular calcium

  21. Doses • 50-200 mg - Sleepy first 5 minutes - Blood levels peak at 30 min. - Stimulant effects • 300-1000 mg • Prolonged ability to perform • Exaggeration of side effects • Pronounced insomnia • Nervousness • Irritability • Tremor • Restlessness • 1000+ mg • “Caffeinism” • All of the above worsen • GI disturbances • Cardiac arrhythmias

  22. Diagnostic Criteria for Caffeine Intoxication A. Recent consumption of caffeine B. Five (or more) of the following develop shortly after caffeine use restlessness nervousness excitement insomnia flushed face diuresis GI disturbances muscle twitching rambling flow of speech tachycardia periods of inexhaustibility psychomotor agitation

  23. Effects on the Body • Central Nervous System • - stimulant • Autonomic Nervous System • - change in EMG activity • Cardiovascular System • - heart and blood vessels • - blood platelets • Gastrointestinal System • - cause for ulcers? • Respiratory • - increases blood and air to lungs

  24. Effects (cont’d) • Skeletal Muscles • - contraction (contrarily) • Energy Metabolism • - basal metabolic rate, free fatty acids, oxidation of fats in exercise • Neurotransmitters • - norepinephrine in CNS, norepinephrine and epinephrine in blood, seratonin in brain • Neuroendicrine effects • - stress (high doses)

  25. Behavioral Effects (w/ 100~200 mg) • Increases wakefulness, alleviates fatigue, facilitates concentration • Can also produce: elevated mood, shaky/jittery feeling • ↑ time to fall asleep,↓ amount and quality of sleep • ↑ attention/vigilance, ability to sustain performance • ↑ work capacity/speed,↓ # of errors Fig. 3-d: Percent change on a repeated acquisition test, which assesses motor learning and memory

  26. Tolerance • Decreased A2a receptor expression • Increased A1 receptor expression • Tolerance to respiratory effects after 8 consecutive days of daily administration • Cross-tolerance • Caffeine tolerance is pharmacodynamic

  27. Overdosing • Very rare but deadly occurrence • LD50= 150mg/kg • 70 kg (154 lbs) person’s lethal dose is 10.5 grams • In 1986, of 2709 cases of caffeine “exposure” registered with Poison Control Centers, 0.1% or 3 cases resulted in death.

  28. Withdrawal • Withdrawal has been reported after stopping a dose as low as 100 mg/day • 40-70% of people who attempt to quit caffeine experience withdrawal • Withdrawal can be totally incapacitating • Onset: 12-24 hours • Peak: 20-48 hours • Duration: 2-7 days

  29. Withdrawal (cont.) • Withdrawal can occur by abstaining from a dose as low as 100mg/day • equivalent to a cup of coffee or 2-3 caffeinated soft drinks. • Telephone survey shows 40-70% of consumers trying to quit reported experiencing withdrawal symptoms

  30. Symptoms of Withdrawal The most commonly reported symptoms of withdrawal are: • Irritability • Depression • Anxiety • Flu-like symptoms • Impairment in psychomotor, vigilance, and cognitive performances • Headache • Fatigue • Sleeplessness/Drowsiness • Difficulty Concentrating • Work Difficulty

  31. Caffeine Addiction • Not included in DSM IV • While caffeine produces physical dependence, there is insufficient information on whether it causes inability to stop use or cause use despite harm.

  32. Medical Uses • Treatment of migraine headaches, caused by dilation of blood vessels • Mixed with ergotamine tartrate (vasoconstrictor) • Increases the power of aspirin and other painkillers by about 40% • has also been used to treat: • chronic obstructive pulmonary disease • asthma • breathing problems in newborns • overdoses with opioid drugs

  33. Other Positive Effects • Weight Loss Effects • Increased Alertness • Enhanced Concentration • Enhance Physical Endurance and Delay Fatigue

  34. Health Problems • 5 or more cups of coffee daily can increase the risk of heart disease due to: - ↑ heart rate - ↑ blood pressure - ↑ blood cholesterol levels • Drinking coffee may cause increase of stress hormones - adrenal gland produces adrenaline until no more can be produced - leads to chronic fatigue, constant exhaustion and susceptibility to disease

  35. Other Negative Effects • Diuresis • Gastritis • Heartburn • Lower birth weights • Pregnancy risks • Panic Attacks • Jitters • Anxiety • Raised Blood Pressure • Insomnia

  36. A Dangerous Combination • Because of risk of increased blood pressure, caffeine should be used cautiously by patients who take other drugs that raise bp • Anti-Depressants that are MAO inhibitors • Marplan, Nardil, and Parnate • High doses of cold medicine • Phenylpropanolamine • Adds to the effects of other stimulants • Cocaine, amphetamines, metamphetamines

  37. Generation Wired (cont.) • Sodas are aggressively marketed for kids • Marketers focus on children starting at the age of 18 months • In order to establish consumer loyalty to their brand, advertisers try to appeal to younger and younger customers • Mountain Dew, the preferred soda of children under 6, distributed a half million free pagers to children in 1998 in an ad campaign

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