After midterm #2 - caffeine and methylxanthines Flashcards
caffeine
best known of methylxanthines
common sources
coffee, tea, chocolate. Coffee cultivation began in Ethiopia
Types of coffee beans
coffee arabica: originates in Ethiopia, grown in South America; 70 % of world coffee production
Coffee caffeine content
100 mg in 5 oz cup (196 mg in 14 oz Tim Horton’s cup)
Tea caffeine content
14-65 mg caffeine in 8 fl oz cup (also contains theobromine and theophylline
Chocolate caffeine content
2 oz milk chocolate contains 3-10 mg caffeine. Chocolate milk ; 2-7 mg in 8 fl oz.
Other sources (3)
Guarana paste from seeds of Paullaina cuppa (4.3% caffeine) most potent natural source, South America.
Cola nuts (2-3.5 % caffeine) chewing nut is widespread habit in Western Africa, use to flavour Coca-Cola and Pepsi-Cola (not as a source of caffeine in them)
Energy drinks: considered dietary supplements, unlike soft drinks (max 71 mg/12 oz) caffeine content not regulated by FDA; contain 50-300 mg caffeine per 8.4 oz; average daily consumption 160 mg from energy drinks.
Pharmacokinetics - Absorption
bases with very low pka (0.5); rapid absorption from GI tract (stomach walls, small intestine)
Peak blood levels after coffee within 45-75 minutes
Pharmacokinetics - distribution
crosses the blood-brain barrier and placental barriers. 10-30% is bound to plasma proteins. Distributes in equal concentrations throughout the body
t 1/2
~5 hours (2.5-7.5 hours)
-
metabolized by liver
about 1% excreted unchanged
Also metabolized by…
cytochrome P 450 enzymes; CYP 1A2 gene codes for enzyme (1A form - rapid metabolism, 1F form = slow metabolism, greater effect, also experience adverse effects
metabolic rate slowed down by
alcohol, grapefruit juice, slower in nonsmokers, women taking oral contraceptives and pregnant women
metabolic rate sped up by
broccoli
Newborns?
can’t metabolize, excrete 85% unchanged, (t1/2 = 100 hours in infants; adult-like metabolism by 7-9 months of age
Neurophysiological effects - methylxanines are ____ blockers (_____)
adenosine receptor blockers (A1, A2a)
neuromodulator acts ______ to _____ inhibit the _______ of _____
neuromodulator acts presynaptically to inhibit the release of NT. Blocking adenosine receptors increases release of NTs (inhibiting adenosine causes acetylcholine neurons to increase their firing rate)
Reinforcing effect:
block A1 receptors on DA terminals in ventral striatum (increase DA release)
High doses of caffeine ____
block BZ receptors; 10 cups block 20% of BZ receptors
Effects on the body – vasodilator in the _____ (5)
Vasodilator in the peripheral NS:
1) stimulates heart rate
2) causes skeletal muscle to strengthen and smooth muscle to relax
3) dilation of bronchial muscles
4) reduces likelihood of fatigue in striated muscles
5) increased urination
stimulates heart rate
dilates the arteries of the heart muscle (reflexive tachycardia); increases blood flow and oxygen to the heart
dilation of bronchial muscles
therapeutic use to ease breathing; theophylline has stronger effects than caffeine
increased urination
increased frequency and urgency of urination, decreased sensation of a full bladder, increased flow rate and volume
- women who consumed more than 450 mg/day had greater risk of urinary incontinence than those that drank less than 150 mg/day
Vasoconstrictor in____
Vasoconstrictor in CNS
- commonly assumed caffeine relieves headaches by constricting blood vessels
- vasodilation is symptom, not cause, of migrane
- adenosine levels increase during a migraine (increase causes vasodilation and pain)
- relief from caffeine is due to blocking adenosine, not vasoconstriction
- caffeine in OTC medications enhances the effectiveness of pain relievers that alleviate pain from headache
Methodological concerns
when participants avoid caffeine prior to assessment, changes in performance may be due to DECREASE IN WITHDRAWAL RATHER THAN IMPROvement from baseline
Effects on human performance
improves athletic performance that requires sub maximal output for long period (country skiing, running, cycling, etc.)
produces insomnia
- 300 mg increases latency to sleep form 18 - 66 min; decreases total sleep time from 475 to 350 minutes
- decreases acoustic arousal threshold; awakened more easily
- can counteract sleep-inducing effects of pentobarbitol
- tolerance to sleep effects develop within a week
Effects with increased doses of caffeine (graphic)
migrane, accelerated heartbeat, muscle tremors, upset stomach, frequent turination, insomnia, nervousness, irritability, restlessness (> 500 mg)
Subjective effects (5 points)
feelings of well-being, alertness, energy, motivation for work, self-confidence
- more likely to be reported by nonusers or users deprived of caffeine
- occur with low doses (20-200 mg)
- caffeine in 1-2 cups of coffee (100-200 mg) decreases fatigue and increases mental alertness
- caffeine in 12-15 cups of coffee (1.5 g) produces anxiety and tremors
Self-administration (nonhumans)
not a robust reinforcer, doesn’t support a lot of behaviour
Self-asministration (humans)
preference for caffeinated coffee and caffeine capsules. People seek effects of caffeine to actively avoid caffeine withdrawal
- task-dependent: diligence task - prefer caffeine capsules beforehand. Relaxation task - only 2/7 prefer caffeine capsules
Tolerance
less effect on heavy drinkers than on non-drinkers of coffee (150 - 300 mg) - jitteriness, nervousness in nonusers but alertness and contentment in users)
- different effects show tolerance at different rates (cardiovascular effects fade in 2-5 days; increase in urination doesn’t show tolerance,
- tolerance due to up regulation of adenosine receptors
- cross- tolerance among methylxanthines
Withdrawal
headache (most common); also drowsiness, fatigue, decrease in energy, impaired concentration, increased irritability, aches and muscle stiffness, decreased feelings of well-being
- severity related to dose (unlike nicotine)
- begins in 12-28 hours, peaks at 20-50 hours, lasts 2-9 days
- physical dependence within 6-14 days (at >/= 600 mg/day)
Caffeine Use Disorder (not a current diagnosis)
DSMV = emerging measures and models: 3 criteria
- persistent desire or unsuccessful efforts to reduce or control caffeine use
- continued caffeine use despite it causing or exacerbating an existing physical or psychological problem
- withdrawal symptoms upon cessation or reduction of caffeine intake
- given increased levels of daily use, risk of over diagnosis
Harmful effects (lethal)
lethal does is 150-200 mg/kg of bodyweight (70 kg x 150 mg = 10 500 mg or 10.5 g) ; 50-100 cups of coffee causes ventricular fibrillation in heart, respiratory collapse and convulsions. ~100 mg /kg in children – causes of accidental death from eating large quantities of caffeine containing medication
Beneficial effects
- lowered risk of Type II diabetes (6 cups/day have 35% less risk than 2 cups/day)
- risk is also lower in those that drink decaffeinated coffee; effect due to ingredient other than caffeine
- protective effects against Parkinson’s disease in men
- caffeine blocks adenosine A2A receptor and increase DA activity; alleviates motor symptoms including tremor and freezing of gait
