Flashcards in 29. Pharmacology of Alcohol PHARM Deck (68)
alcohol marked as 150 proof is what % alc?
proof = %alc by volume *2
150 proof is 75% alcohol by vol.
what three systems does alcohol have effect on?
what does alcohol do to the GABA system? what is the effect?
binds to GABA-A receptor, increasing GABA effect. effect = relaxation, loss of coordination, motor slowing, sedative, anxiolytic. (enhances inhibition)
GABA's major action: inhibitory or excitatory?
what does alcohol do to the glutamate system? what is the effect?
NMDA antagonist: inhibits release of presynaptic glutamate. also reduces actions of glutamate at the post-synaptic neuron receptors so DOUBLE EFFECT.
what is the effect? sedation, impaired memory, impaired cognition, hypnotic.
glutamate's major action? inhibitory or excitatory?
what does alcohol do to the opioid system? what is the effect?
indirect stimulation of beta-endorphins. effect = pleasurable euphoric effects via mu receptors
what does alcohol do to the dopamine system? what is the effect?
indirect stimulation of dopamine neurons in the VTA. effect = dopa release, pleasure/reward.
at the neuron level, what does alc do to beta-endorphin pathways?
stimulates these pathways from the arcuate nucleus; effect is release of dopamine into the nucleus accumbens -> pleasure/reward
also inhibits GABAergic neurons in the VTA, which allows for release of more dopa.
another DOUBLE EFFECT.
chronic exposure to alcohol does what to the GABA system?
decreased density of the GABA receptors leading to tolerance/neuroadaptation
chronic exposure to alcohol does what to the glutamate system?
compensatory increase in NMDA activity and receptor density leading to tolerance/neuroadaptation
extremely condensed version of alc's effects on GABA, glutamate, endorphin systems?
agonizes GABA (incr inhibition)
antagonizes NMDA/glutamate (decr excitation)
indirect action on opioid, dopamine
why do women metabolize alcohol more slowly?
smaller amount of body water, also lower activity of gastric enzyme ADH, which metabolizes alc.
where is ethanol primarily metabolized?
small amounts excreted unchanged
90% removed by oxidation which occurs in the LIVER.
describe the pharmacokinetics of ethanol metabolism - the biochemical pathway.
Ethanol --> (alcohol dehydrogenase) --> Acetaldehyde --> (aldehyde dehydrogenase) --> Acetate --> (CoA) --> Acetyl-CoA --> Co2, water, calories
how is alcohol metabolized in the GI tract?
ADH in stomach and small intestine.
early metabolism translates to lower BAC levels??
what order kinetics does alcohol metabolism follow in the liver?
zero order kinetics once enzymes (specifically ADH) are saturated. (ie, a constant amount of ethanol is eliminated per unit of time).
what amt of BAC can someone metabolize in an hour? have there been outliers from this average?
plasma clearance: generally 0.015 per hour.
group of swedish people has higher rate (prob genetic)
rate increases with alc dependence: some alcoholics can metabolize 0.02 or 0.025 per hr.
how many drinks can someone metabolize in an hour?
slightly less than 1. (1.5 oz of 80 proof, 1 oz of 100 proof)
so if you drink 1 per hour, your BAC will rise somewhat but you won't be over the legal limit for over 7 hours
the first step of alcohol metabolism requires what as a cofactor?
NAD molecule. This is the first of 2 rate-limiting steps (ethanol to acetaldehyde using alcohol dehydrogenase as an enzyme).
what are 4 changes in chemistries that happens with chronic alcohol use?
1. incr production of lactic acid, can result in hyperuricemia and gout
2. incr production of ketone bodies --> ketonemia
3. incr triglyceride synthesis results in a fatty liver
4. decreased gluconeogenesis and liver glycogen cause hypoglycemia
what system allows alcoholics to metabolize alcohol at increased rates from average drinkers?
the Microsomal Ethanol Oxidizing System (MEOS). In liver. With BACs in normal range, this system contributes little to metabolism. With BACs over 0.1, this system kicks in. Uses NADPH as a cofactor rather than NAD
acetaldehyde metabolism occurs where?
how many NAD molecules required to oxidize 1 ethanol molecule?
second rate-limiting step in alcohol metabolism?
acetaldehyde --> acetate using NAD and aldehyde dehydrogenase.
accumulation of what molecule leads to hangovers?
acetaldehyde. directly between the two rate-limiting steps of metabolism.
disulfiram is the generic name for what?
where does disulfiram work? what does it cause?
blocks aldehyde dehydrogenase, which converts acetaldehyde to acetate. causes backup of acetaldehyde; extreme discomfort in people who drink alcohol.
when BAC gets to very high levels (0.3, 0.4) a person will have problems with what?
maintaining homeostasis. Pulse, temp, BP , RR will all DROP to dangerous levels. may be incontinent. could result in death.