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
Caffeine (1, 3, 7trimethylxanthine) found in coffee, sodas and some OTC medicine Theophylline (1, 5dimethylxanthine) found in tea Theobromine (3, 7dimethylxanthine) found in chocolate
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. 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 for young people to hang out Marketing of cold-sweet coffee drinks and 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
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. 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 softdrink companies High-Energy Cocktails 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
Anheuser-Buschs 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 AnheuserBusch, 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) 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 and 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 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 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 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 Mechanisms of Action Multiple mechanisms Adenosine antagonist - both A1 and A2 sites
2nd messenger theory - Phosphodiesterase inhibition - cAMP, AMP, intracellular calcium 50-200 mg Doses - 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 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 flushed face GI disturbances rambling flow of speech periods of inexhaustibility
insomnia diuresis muscle twitching tachycardia psychomotor agitation 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 Effects (contd) 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) 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 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) persons 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 4070% of consumers trying to quit reported experiencing withdrawal symptoms Symptoms of Withdrawal The most commonly reported symptoms of withdrawal are: Headache Irritability Fatigue
Depression Sleeplessness/Drowsiness Anxiety Difficulty Concentrating Flu-like symptoms Work Difficulty Impairment in psychomotor, vigilance, and
cognitive performances 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. 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 Other Positive Effects
Weight Loss Effects Increased Alertness Enhanced Concentration Enhance Physical Endurance and Delay Fatigue 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 Other Negative Effects
Jitters Anxiety Raised Blood Pressure Insomnia 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 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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