CAFFEINE Caffeine Basics Methylxanthines History History (cont.)

CAFFEINE Caffeine Basics Methylxanthines History History (cont.) www.phwiki.com

CAFFEINE Caffeine Basics Methylxanthines History History (cont.)

Finebaum, Paul, Host has reference to this Academic Journal, PHwiki organized this Journal 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 as long as m Methylxanthines Caffeine (1, 3, 7-trimethylxanthine) – found in coffee, sodas in addition to some OTC medicine Theophylline (1, 5-dimethylxanthine) – found in tea Theobromine (3, 7-dimethylxanthine) – found in chocolate

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History Plants evolve caffeine to protect themselves from attack by bacteria, fungi in addition to 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. 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 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).

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 as long as young people to hang out Marketing of ‘cold-sweet’ coffee drinks in addition to high caffeine sports/energy drinks 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 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 as long as every man woman in addition to child in America.

Profiting Schools Soda companies pay school districts as long as exclusive selling rights (Coke vs Pepsi) in addition to as long as the right to put ads on the gym walls in addition to 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 High-Energy Cocktails mixture of energy drinks in addition to alcohol sold as expensive cocktails in many clubs 100mg of caffeine – often sold without labels Dangerous when combined with alcohol 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 as long as contemporary adults who are looking as long as the latest beverage to keep up with their highly social in addition to fast-paced lifestyles. 54 mg of caffeine (plus guarana in addition to ginseng)

Pharmacokinetics: Route of Administration/Absorption Absorption through: Stomach Small intestine Large intestine Effects of caffeine Depends on: Food in the body Caffeine in the substance Distribution Throughout the body in addition to the brain Water soluble Crosses blood brain barrier Reaches the fetus No accumulation within body 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

Metabolism The enzyme CYP1A2 is responsible as long as the metabolism of caffeine in the liver. One as long as m of the enzyme, produced by the gene variant 1A, metabolizes caffeine rapidly while another as long as m, 1F, metabolizes it slowly. Shorter/Faster Metabolism if: Cigarettes Caucasians Women Child Longer/Slower Metabolism if: Alcohol Asians Men Newborn Liver Damage Pregnant Metabolism Smoking Will Metabolize Twice as Fast Alcohol Will Metabolize Slowly Metabolism & Excretion Metabolized by liver (first-order kinetics) Excreted by kidney via urine (diuretic)

Pharmacodynamics Main mechanism of action: direct competitive antagonist of adenosine receptors – A1 in addition to A2a Effects on Monoamines: -Elevates levels of 5-HT in the brain -Stimulates NE neurons -Increases rate of DA as long as mation 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 Mechanisms of Action Multiple mechanisms Adenosine antagonist – both A1 in addition to A2 sites 2nd messenger theory – Phosphodiesterase inhibition – cAMP, AMP, intracellular calcium Doses 50-200 mg – Sleepy first 5 minutes – Blood levels peak at 30 min. – Stimulant effects 300-1000 mg Prolonged ability to per as long as m Exaggeration of side effects Pronounced insomnia Nervousness Irritability Tremor Restlessness 1000+ mg “Caffeinism” All of the above worsen GI disturbances Cardiac arrhythmias

Diagnostic Criteria as long as 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 Effects on the Body Central Nervous System – stimulant Autonomic Nervous System – change in EMG activity Cardiovascular System – heart in addition to blood vessels – blood platelets Gastrointestinal System – cause as long as ulcers Respiratory – increases blood in addition to air to lungs 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 in addition to epinephrine in blood, seratonin in brain Neuroendicrine effects – stress (high doses)

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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 in addition to quality of sleep attention/vigilance, ability to sustain per as long as mance work capacity/speed, of errors Fig. 3-d: Percent change on a repeated acquisition test, which assesses motor learning in addition to memory 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 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.

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 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 Symptoms of Withdrawal The most commonly reported symptoms of withdrawal are: Headache Fatigue Sleeplessness/Drowsiness Difficulty Concentrating Work Difficulty Irritability Depression Anxiety Flu-like symptoms Impairment in psychomotor, vigilance, in addition to cognitive per as long as mances

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, in addition to Parnate High doses of cold medicine Phenylpropanolamine Adds to the effects of other stimulants Cocaine, amphetamines, metamphetamines Generation Wired (cont.) Sodas are aggressively marketed as long as kids Marketers focus on children starting at the age of 18 months In order to establish consumer loyalty to their br in addition to , advertisers try to appeal to younger in addition to 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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