Psychostimulants: caffeine and nicotine Flashcards
What % consume coffee?
What are the amounts of caffeine in mg in a cup of coffee, a can of pop, and excedrin?
80% of adult population
Cup o joe - 100/135mg
Pop - 40mg
Excedrin - 65mg
What is caffeine’s chemical name? analogs?
Xanthine alkaloid - guaranine/mateine/theine
What are the pharmacokinetics of caffeine? (absorption, peak plasma, distribution and excretion)
Rapidly and completely absorbed
Peak plasma levels at 45m
Freely and equally distributed throughout the total body
2-3% of the drug is excreted unchanged
What are the structural components of caffeine?
Hint: 3
Paraxanthine - increases lipolysis (is a metabolizer)
Theobromine - dilates blood vessels and increases urine volume (more blood and pee)
Theophylline - relaxes smooth muscle of bronchi, used to treat asthma
What component metabolizes caffeine? what component can jeopardize the function of this metabolizer?
Caffeine is metabolized by CYP1A2
Fluvoxamine (SSRI) is a potent inhibitor of CYP1A2 - if you take fluvox you could OD on caffeine
What is the half-life of caffeine? What is the result of reasonable consumption? what is the results of heavy consumption? what is the lethal dose?
Half life of 2.5 to 10 hours - extended in infants, pregnant, elderly
Moderate: CNS and metabolic stimulant - restore mental alertness and wakefulness
Heavy: Agitation, anxiety, tremors, insomnia
Lethal: 10g (approx 100 cups of coffee)
What are the CNS and PNS symptoms of the overuse of caffeine? (anxiogenic effects)
Doses higher than 1g (10 cups)
CNS - anxiety, agitation, insomnia
PNS - tachycardia/hypertension/GI
What does caffeine do to the heart? What does constricting the cerebral blood vessels help with?
Increases cardiac contractility and output - not good if you have cardiac complications
Dilates coronary arteries, more O2
Constricts cerebral blood vessels, less O2 - can help with headaches caused by brain puff
What are the physical actions of caffeine? (base functions)
Bronchial relaxation
Increased secretion of gastric acid - digestive
Increased urine output
What is the mechanism of caffeine?
Adenosine antagonist and a competitive inhibitor
Adenosine - sedative properties (stimulate GABAergic neurons in DA reward system in prefrontal cortex - not nucleus accumbens)
Indirect effects
What is the limit for adults per day? What are the birth effects?
400mg a day - pregnant limit to 300mg a day
Small doses - can have modest degree of fetal growth restriction
Large doses may increase risk of miscarriage, but no effect on birth weight or ADHD
What are the pharmacokinetics of nicotine? (Absorption, half-life)
Readily absorbed from every site - reaches brain in 7 sec
Half life of 2 hours
Nicotine levels saturate - achieve 15mg/l (1-2mg of nic)
Only 20% of nicotine is absorbed from cig (0.5 to 3mg)
Which enzyme metabolizes nicotine?
Hepatic enzyme, CYP-2A6
Produces metabolite - cotinine
- can remain in blood for 48hrs
- used as biomarker for tobacco use
Where is nAChR found in the CNS?
Presynaptic nerve terminals of - dopamine neurons, acetylcholine neurons, glutamate neurons
Increases DA levels in limbic system
Nicotine attaches to the a4b2 nACh receptor
Displaces 75% of radiolabeled tracer after 3 cigs
What are the pharmacological effects of continued nicotine use?
Early stages - nausea, vomitting
Stimulates hypoT, releases ADH (causes fluid retention)
Nicotine causes
- decreased muscle tone
- appetite suppression, weight loss
Increased blood flow to arousal/reward centers - antidepressant effects
