After midterm #2 - caffeine and methylxanthines

Question 1

caffeine

Answer 1

best known of methylxanthines

Question 2

common sources

Answer 2

coffee, tea, chocolate. Coffee cultivation began in Ethiopia

Question 3

Types of coffee beans

Answer 3

coffee arabica: originates in Ethiopia, grown in South America; 70 % of world coffee production

Question 4

Coffee caffeine content

Answer 4

100 mg in 5 oz cup (196 mg in 14 oz Tim Horton’s cup)

Question 5

Tea caffeine content

Answer 5

14-65 mg caffeine in 8 fl oz cup (also contains theobromine and theophylline

Question 6

Chocolate caffeine content

Answer 6

2 oz milk chocolate contains 3-10 mg caffeine. Chocolate milk ; 2-7 mg in 8 fl oz.

Question 7

Other sources (3)

Answer 7

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.

Question 8

Pharmacokinetics - Absorption

Answer 8

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

Question 9

Pharmacokinetics - distribution

Answer 9

crosses the blood-brain barrier and placental barriers. 10-30% is bound to plasma proteins. Distributes in equal concentrations throughout the body

Question 10

t 1/2

Answer 10

~5 hours (2.5-7.5 hours)

-

Question 11

metabolized by liver

Answer 11

about 1% excreted unchanged

Question 12

Also metabolized by…

Answer 12

cytochrome P 450 enzymes; CYP 1A2 gene codes for enzyme (1A form - rapid metabolism, 1F form = slow metabolism, greater effect, also experience adverse effects

Question 13

metabolic rate slowed down by

Answer 13

alcohol, grapefruit juice, slower in nonsmokers, women taking oral contraceptives and pregnant women

Question 14

metabolic rate sped up by

Answer 14

broccoli

Question 15

Newborns?

Answer 15

can’t metabolize, excrete 85% unchanged, (t1/2 = 100 hours in infants; adult-like metabolism by 7-9 months of age

Question 16

Neurophysiological effects - methylxanines are ____ blockers (_____)

Answer 16

adenosine receptor blockers (A1, A2a)

Question 17

neuromodulator acts ______ to _____ inhibit the _______ of _____

Answer 17

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)

Question 18

Reinforcing effect:

Answer 18

block A1 receptors on DA terminals in ventral striatum (increase DA release)

Question 19

High doses of caffeine ____

Answer 19

block BZ receptors; 10 cups block 20% of BZ receptors

Question 20

Effects on the body – vasodilator in the _____ (5)

Answer 20

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

Question 21

stimulates heart rate

Answer 21

dilates the arteries of the heart muscle (reflexive tachycardia); increases blood flow and oxygen to the heart

Question 22

dilation of bronchial muscles

Answer 22

therapeutic use to ease breathing; theophylline has stronger effects than caffeine

Question 23

increased urination

Answer 23

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

Question 24

Vasoconstrictor in____

Answer 24

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

Question 25

Methodological concerns

Answer 25

when participants avoid caffeine prior to assessment, changes in performance may be due to DECREASE IN WITHDRAWAL RATHER THAN IMPROvement from baseline

Question 26

Effects on human performance

Answer 26

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

Question 27

Effects with increased doses of caffeine (graphic)

Answer 27

migrane, accelerated heartbeat, muscle tremors, upset stomach, frequent turination, insomnia, nervousness, irritability, restlessness (> 500 mg)

Question 28

Subjective effects (5 points)

Answer 28

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

Question 29

Self-administration (nonhumans)

Answer 29

not a robust reinforcer, doesn't support a lot of behaviour

Question 30

Self-asministration (humans)

Answer 30

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

Question 31

Tolerance

Answer 31

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

Question 32

Withdrawal

Answer 32

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)

Question 33

Caffeine Use Disorder (not a current diagnosis)

Answer 33

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

Question 34

Harmful effects (lethal)

Answer 34

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

Question 35

Beneficial effects

Answer 35

- 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