Exam 2: Caffeine Flashcards
what is the most widely used psychoactive substance in the world?
caffeine
caffeine
mild psychostimulant of Xanthine family
- found in many plants : originally evolved to protect plants from insects, bacteria, fungi
where is caffeine found
coffees, sodas, some OTC medications
where is theophylline found
tea
where is theobromine found
chocolate
what drink has the highest amount of caffeine vs the lowst
highest: coffee
lowest: tea
Route of administration for caffeine
orally mostly
absorption of caffeine
- completely absorbed from GI tract - in 30-60 min
- plasma half life: 4-6hrs
- repeated caffeine drinking throughout day inc plasma caffeine level gradually
distribution of caffeine
throughout brain and body
NO accumulation within the body - no depot binding sites
readily passes through membranes like BBB
metabolism of caffeine
broken down into 3 active metabolites
-paraxathine, theobromine, theophylline
active metabolite that does lipolysis
- mobilizes stored energy in fat during fasting or exercise - why some people consume during weightloss
major metabolite
paraxathine
metabolite that dilates blood vessels and inc urine production
theobromine
metabolite that relaxes smooth muscles of bronchi - used to treat asthma
can cause nausea, irregular heartbeat
theophylline
what 2 active metabolites of caffeine are found in tea and chocolate
theobromine and theophylline
caffeine metabolism is slower if
men, pregnant women, newborns
used ith birth control pills
liver damage -since caffeine metabolized in liver
asian population
caffeine is metabolized faster if
used with cigarettes
women, children
caucassian population
excretion of caffeine
first order kinetics-exponential, half life
in urine:
- 95% as metabolites (mainly paraxathine)
-5% as unchanged in urine
pharmacodynamics of caffeine: its diverse actions in brain
adenosine receptor antagonism!!!!
high doses:
- GABA A receptor antagonism
-inc in Ca within cells - more likely to fire action potential
what is adenosine created from
breakdown of ATP
- astrocytes and neurons release energy carrying ATP molecules
or
as a byproduct in gluconeogenesis - glycogen to glucose
what mobilizes glycogen from storage
monitors glucose levels, if low recruits it from storage
astrocytes
4 receptor subtypes of adenosine and which mediate most adenosine effects in the brain - respond to caffeine
A1, A2A, A2B, A3
A1R and A2AR mediate most adenosine in the brain
where are A2A receptors found
striatal GABAergic projecting neurons (indirect pathway)
and nucleus accumbens
striatal A2A receptors form heteromers with what
dopamine D2 receptors - indirect pathway neurons
A2A receptor occupancy by adenosine has what effect on the D2 receptor
allosteric influence
- reducing the sensitivity to dopamine decreasing arousal and altering the motor effects of dopamine
caffeine is a ________ for metabotropic adenosine receptors
competitive antagonist
blocking adenosine receptors…
enhances dopamine D2 receptor signaling
- get mild arousal and psychomotor activation
inc in movement by activating D2
where are adenosine receptors found
heart and kidneys
- diuretics : inc the amount of water expelled form the body
caffeine activates what nervous system and what does it cause
sympathetic nervous system
coronary artery vasodilator and bronchodilation
- inc HR
- constricts cerebral arteries (inc BP)
- inc respirations
induces fight or flight when no stress
benefits of caffeine
- daily consumption of 400mg poses little to no risky for healthy ppl
- mental performance: inc alertness, attention, rxn time
- physical performance: inc endurance, delayed fatigue
- imprved migraine symptoms if take at onset - constricted blood vessels
caffeine intoxication effects and level
more than 500mg a day
- panic attacks, nausea, clumsinesss, restlessness, GI isturbances, insomnia, muscle twitching
- heart palpitations, tachycardia, high BP, nausea, seizures, metabolic aciosis (kidney dysfunction
can caffeine kill you? lethal dose?
LD50=150-200mg caffeine/kg bodyweight
calculate
If you drink a big coffee (200mg) at 3pm, how much will still be in your system at 9pm, and when will it all be gone?
at 9pm: 100mg will be left
all gone: 6 half lives - for a halflife of 4 hours : 24 hrs for 6 hrs: 36 hrs
when would you need to stop drinking coffee to ensure good sleep?
12pm
caffeine with alcohol…
ethanol consumption increases adenosine
- makes you feel sleepy - drinking alcohol has sedative effects
caffeine prevents the activation of what?
adenosine receptors
- reduced fatigue
masks sedative effects of alcohol
what might slow down the clearance of alcohol from your system
zero order kinetics
tolerance and caffeine
-chronic use leads to tolerance for subjective effects, cardiovascular and respiratory effects, disrupts sleep
high doses of caffeine (750-1200mg/day) can produce
complete tolerance in some individuals
- no longer getting benefits from caffeine
dependence and caffeine
mild seen in individuals chronically using >100mg a day
NOT recognized as substance abuse by DSM-5
withdrawal symptoms with caffeine
headache, fatigue, drowsiness, difficulty concentrating, irritability, depression, anxiety, impaired motor abilities, cognitive performance
headaches and caffeine
in 1st week not many headaches but once first day of placebo there is a spike in headaches
fatigue and caffeine
takes longer to stabilize over time than the headaches - 405 days
