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Pharmacology and Toxicology
PHAR 100
Hisham Elbatarny

Stimulant Drugs - Caffeine and Nicotine Caffeine: Introduction • most widely and regularly used drug in the world • common concentrations ◦ 1 cup (8 oz) of coffee: 100-150 mg caffeine ◦ 1 cup (8 oz) of tea: 40-80 mg caffeine ◦ 12 fl. oz can of cola: 35-65 mg caffeine ◦ milk chocolate bar: 20 mg caffeine • “Energy Drinks” fortified with extra-large amounts of caffeine ◦ Rockstar: 16 oz, 160 mg caffeine ◦ Red Bull: 8.3 oz, 80 mg caffeine Caffeine: Introduction • member of a family of drugs called methylxanthines • naturally occurring in a number of species of plants: found in coffee, tea and chocolate • first isolated from coffee by German chemist: called Kaffeebase History of Coffee • coffee is made from the fruit of a small tree: genus Coffea • Dr. William Harvey was one of the first coffee drinkers in England and promoted the beverage for its therapeutic benefits • two of his students believed it cured drunkenness • coffee gained such popularity in England, consumption of alcoholic beverages started to decline History of Tea • sold commercially in China by 780AD • 1630s: Dutch started shipping tea to Europe, Germany and France • becamrda major export from England in 1760 ◦ 3 largest export from Britain to the colonies • tea smuggling: tea tax on all tea imported into Britain History of Cocoa • first cultivated by Mayans of the Yucatan Peninsula, Aztecs of Mexico and Incas of Peru • believed it was a gift from the gods • recognized as a food for the wealthy and noble • as cost decreased, and processing cocoa became more streamlined, chocolate was consumed as a confection Caffeine: Pharmacokinetics Route of administration: oral • rapidly and completely absorbed • plasma levels peak about 90 min after consumption • freely crosses the placenta Metabolism occurs in the liver • “fast” and “slow” metabolizers ◦ fast: break down caffeine quicker than others, need more to get same level of alertness ◦ slow: sticks around in body for longer, need less than average person • in smokers, duration of action is shortened: nicotine increases metabolism of caffeince • duration of action extended in ◦ infants: don't have same number of enzymatic activity in liver ◦ pregnant women: second trimester duration of action of caffeine is doubled what it would normally be, while third trimester is triple ◦ and the elderly: as age number of enzymes in liver decreases Caffeine: Pharmacological Effects (100-250 mg) CNS: • cerebral cortex ◦ increased mental performance ◦ decreased drowsiness and fatigue ◦ enhanced motor activity • medulla ◦ stimulation of respiratory and vasomotor centres ◦ increased respiration and heart rate Cardiovascular system: • increased heart rate and blood pressure (low dose) • heart rhythm disturbance (high dose) Caffeine: Pharmacological Effects • CNS stimulant • lethal dose: 10 grams (100 cups of coffee) • Caffeinism: clinical syndrome ◦ overuse or overdose ◦ CNS Symptoms: increased anxiety, hypertension (increased blood pressure), tachycardia (increased heart rate), GI disturbances • PNS Symptoms: ◦ increased cardiac contractility and output ◦ constricts cerebral blood vessels – decreases blood flow to the brain and reduces pressure in the brain (relief from headaches) Caffeine: Mechanism of Action • stimulant activity • adenosine receptor antagonist • blocks adenosine mediated activity • Adenosine activity ◦ exerts an inhibitory effect on a number of neurons and transmitters ◦ adenosine activity exerts sedative actions ◦ blocking these effects leads to increased vigilance and mental acuity ← adenosine prepares bodyfor sleep Caffeine: Mechanism of Action • adenosine activity stimulates GABAergic neuron activity ◦ activating GABAergic neurons causes inhibition • caffeine inhibits (blocks) adenosine-mediated activation of GABAergic neurons ◦ leads to excitation Caffeine: Physiological Effects Short-Term: Low Dose • CNS: mild mood elevation, fatigue reduction, can interfere with sleep, nervousness (caffeine- naïve) • Cardiovascular: constricts cerebral blood vessels (helps with headache), increases peripheral blood flow, stimulates cardiac muscle • Respiration: mild stimulation of respiratory rate, relaxation of bronchial smooth muscle Short-Term: High Dose • CNS: irritability, restlessness, insomnia, rambling flow of thought and speech • Cardiovascular: rapid and irregular heartbeat Long-Term Use: Excess use • restlessness, nervousness, insomnia, increased urinary output, gastric upset • no definite link between caffeine consumption and disease states Caffeine: Drug Dependence • chronic use is associated with habituation and tolerance • withdrawal symptoms if discontinued: headache, fatigue • addiction does occur • symptoms last 1-2 days: usually cease within a few days Caffeine: Abuse Potential • low • “high” experienced is mild • inherent harmfulness is very low: increase abuse potential, but “high” is mild • low to moderate intake of caffeine does not appear to be associated with adverse events • larger doses will result in irritability, nervousness, insomnia, and irregular rhythm of the heart Nicotine • 19.9% of Canadians 12 yr or older smoke: 5.8 million Canadians • worldwide about 1.1 billion (22%) of people smoke ◦ 80% live in low- or middle-income countries • every 11 minutes, a Canadian dies from tobacco use
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