Pharm of Alch Flashcards
how does alcohol work as an NT?
GABA A agonist–>increases effect
NMDA/glutamate antagonist–>inhibits release of glutamate
HABA major action
inhibitory
–relaxation, loss of coordination, motor slowing
net effects of glutamate antagonism
sedation
impaired memory
impaired cognition
how do opioids work?
indirect stimulation of b endorphins
–>pleasurable, euphoric effects via mu receptors
two ways that alcohol inhibits glutamate system
Presyn action on meGluR and presyn voltage-sens Ca channels–>inhibit glutamate release
inhibit post-synp ionotrpic glutamate receptors (NMDA)
chronic exposure to alcohol
compensatory increase in NMDA activity and R density leads to tolerance
rate limiting step of alcohol metabolism
oxidation of each ethanol molecule requires 2 NAD+
–limited supply of NAD+ in the liver
where does alcohol go?
2-10% excreted in urine
~90% removed by oxidation
what causes a hang over?
acetaldehyde
cystolic increase in NADH/NAD+ drives 4 biochemical pathways:
- inc. production of lactic acid–>hyperuricemia & gout
- inc ketone bodies–>ketosis
- inc triglyceride synthesis–>fatty liver
- inc gluconeogenesis and liver glycogen–>hypoglycemia
microsomal liver enzyme
as the concentration of ethanol increases above 100 mg/dl, there is an increased contribution of MEOS, therefore increased NADPH (via cytochrome p450)
acetyladehyde metabolism
acetyladehyde–aldehyde dehydrogenase–> acetate–>CO2 and H20–>acetyl-CoA
Disulfiram/Antabuse
inhibitor of ALDH–> acetaldehyde accumulates
-causes extreme discomfort in patients who drink alcoholic beverages
metabolism in GI tract
ADH in stomach and small intestine
proof
% alcohol by volume x 2
BAC
weight of alcohol per volume of blood, measured in mg of alcohol per 100cc of blood
worsening, decrease in temp, decrease in bp, excessive sleepiness, amnesia
0.30-0.40 300-400%
mood, behavioral changes
reduced coordination
impaired driving, machinery operation
20-100mg% (0.02-0.1)
unresponsiveness
serious decrease in pulse, temp, bp, resp
urinary and bowel incontinence
400-800%
0.40-0.80
markedly impaired thinking, memory, coordination
marked reduction in level of alertness
memory black outs
nausea and vomiting
200-300 mg%
0.20-0.30
nervous system adverse alcohol effect
generalized symmetric peripheral nerve injury
Wernicke-Korasakoff encephalopathy is because of
a thiamine deficiency
Werncke’s enceph
Opthalmoplegia
nystagmus
ataxia
confusion
Korsakoff’s psychosis
anterograde and retrograde amnesia
confabulation
lack of insight
apathy
liver disease track
alcoholic fatty liver–>alcoholic hepatitis–>cirrhosis–>liver failure
how does tolerance develop
- induction of hepatic enzymes with increased metabolism
- neuroadaptation–>induction dec GABA inc glutamate, inc dopamine
alcohol withdrawal is problematic because
increased glut
decreased GABA
decreased DA
primary goals of treatment of alcohol withdrawl syndrome
prevent serizures
delirium
werickes
days of withdrawal for seizures
1-2
days of withdarwal for remors
peak at 3-4
purpose of thiamine
helps correct nerve problems due to ack of thiamine in WKS
how is thiamine absorbed and metablolized
abosrbed- GI
metab- liver
lorazapam class-
benzo
GABA modulator
lorazapa/librium mechanism
binds to central benzo receptors–>interact allosterically to potetiate effect of inhibitory GABA
librium/chloradiazepoxide issues
build up of active metabolites makes it less appropriate for eldely, hepatic metabolism bad for liver disease, cog effects persist for days-weeks
chloradiazepoxide benefit
logner acting
Gabapentin class
GABA analogue, anticonvulsant
gabapentin action
interacts with voltage gated Ca channels
Gabapentin benifits vs. disadvantages
benefits- non addictive
disadvantages- not FDA approved for this- not or high risk pts
Naltrexone class
opiod antgonist
most common adverse effect of naltrexone
nausea
disadvantage of naltrexone
cant use with patients on opiates
non-compliance
topiramate class
anti epileptic
topiramate mechanism
blocking of voltage-gated Na+ channels,
augmentation of GABA at GABAR
antag of AMPA
topiramax avantages
more robust than naltrexone
topiramax disadvantages
not fda approved
acamprosate class
analogue of GABA
acamprosate action
NMDA antaonist + GABA R activator
may restore neuronal excitation and inhibit balance
acamprosate adverse effects
caution in depressed patients or renal impairment patients
gabapentin alcohol mech
not active at gabaR
modulates synthesis of GABA and glutamate release resulting in net + GABA effect
