CAFFEINE

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CAFFEINE
The most widely consumed psychoactive substance
in the world.

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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

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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

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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.
  

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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

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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).

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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

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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

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Caffeine Contents

• 7-Up 0 mg
• Root Beer (non-Barqs) 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.

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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

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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

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• 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 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)

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Pharmacokinetics Route of Administration/Absorp
tion

• Absorption through
• Stomach
• Small intestine
• Large intestine

• Effects of caffeine Depends on
• Food in the body
• Caffeine in the substance

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Distribution

• Throughout the body and the brain
• Water soluble
• Crosses blood brain barrier
• Reaches the fetus
• No accumulation within body

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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

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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

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Metabolism

• Smoking Will Metabolize Twice as Fast

• Alcohol Will Metabolize Slowly

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Metabolism Excretion

• Metabolized by liver (first-order kinetics)

• Excreted by kidney via urine (diuretic)

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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

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Mechanisms of Action

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

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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

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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

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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

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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)

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Behavioral Effects (w/ 100200 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
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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

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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.

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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

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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

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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

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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.

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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

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Other Positive Effects

• Weight Loss Effects
• Increased Alertness
• Enhanced Concentration
• Enhance Physical Endurance and Delay Fatigue

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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

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Other Negative Effects

• Diuresis
• Gastritis
• Heartburn
• Lower birth weights
• Pregnancy risks
• Panic Attacks
• Jitters
• Anxiety
• Raised Blood Pressure
• Insomnia

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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

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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