Sweatman Alcohol: Use and Abuse Flashcards
toxicants
ethanol
methanol
ethylene glycol
antidotes for ethanol
disulfuram
antidote for methanol
fomepizole or ethanol
antidote for ethylene glycol
ethanol or fomepizole
drugs for ethanol withdrawal
diazepam
thiamine (B1)
drugs for chronic alcoholics
disulfiram
naltrexone
acamprosate
tx for acute methanol or ethylene glycol poisoning
ethanol or fomepizole
break down of ethanol
ethanol–>acetaldehyde–>acetate
ethanol to aldehyde enzyme
ALCOHOL dehydrogenase
aldehyde to acetate enzyme
Acetaldehyde dehyrogenase
order kinetics for alchohol
zero order
*constant mass–> different proportion
Is alcohol metabolism CYP mediated
very little unless chronic alcholism–>some cyp induction can occur and become more substantiative
Alcohol dehydrogenase blocker
fomepizole
aldehyde dehydrogenase blocker
disulfiram
metabolism of ETOh requires excess of what
NAD+
zero order kinetics
ethanol
phenytoin
aspirin (high dose)
disulfiram MOA
aldehyde dehydrogenase atangonist–> leads to accumulation of acetaldehyde–> nause flushed skin
encourages abstinence from alcohol (antebuse)
disulfiram
Aian flush
SNP’s in acetaldehyde dehydrogenase enzyme–> result is loss of functionality and build up of acetaldehyde–> nasuea, vomiting and flushing of skin
Why some alcoholics find acetaldehyde pleasurable
- unplaseant in periphery
* in the VTA it can lead to dopamine release –> CONDENSES WITH DOPAMINE TO FORM SALSOLINOL–> REINFORCING AGENT
ETHANOL IS AN IMPORTANT INDUCER OR
CYP 2E1
ETOH induction of CYP leads to increased amounts of
NAPQI–> highly toxic
acetominophin is metoblized in three ways
Sulfate conjugation–>major and non-toxic
Glucuronide–> major and non-toxic
NAPQI–> minor and highly toxic (quickly converted to non-toxic thang if GSH stores are high)
mechanism for acetominophen toxicity in chronic alcoholic
etoh induces CYP 2E1–> over production of NAPQI–> GSH stores run out and unable to conjugate NAPQI to non-toxic intermediate–>hepatotoxicity
antedote for acetominophen toxicity
N acetyl cystein–> restores conjugate substrate for metab to non-toxic intermediate
level with limited muscular incoordination
< 50
pronounced incoordinatio
50-100
mood and personality changes, intoxication over legal limit in most states
100-150
nusea vomiting, ataxia, amnesia, dysarthria
150-400
coma, resp failure, death
> 400
ETOH receptors in the brain
NONE –modulates other pathways
Key pathways modulated by ETOH in brain
- reinforcement of inhibitory actions of GABA
2. inhibition of stimulatory actions of Glutamate
blackouts are because of what
inhibition of stimulatory actions of glutamate system
other acute effects of ETOH
relaxes uterine smooth muscle
relaxes vascular smooth muscle
->vasodilation, hypthermia, increased gastric blood flow
CV depressant
can alcohol in small doses prevent premature labor
yes
within body ETOH distribution depends on
total body water
0.5-0.7 L/Kg
does alcohol distribute to body fat
NO
higher BMI=
high BAL
*alcohol would be excluded from this compartment
more weight=
lower BAL
*larger total volume of distribution
female sex=
higher BAL
- weight is less
- more fat
- increased absoprtion
Most common neurologic defect in the alcoholic
peripheral neuropathy
thiamine deficiency results in
Wernicke-Korsakoff syndrome
classic WK tirad
> occulomotor defects (nystagmus) 30%
ataxia cerebellar dysfunction
confusion altered mental state 80%
Ultimate consequence of thiamine deficiency
inability to synthesize and replenish critical amino acids and proteins, especially those in the brain
*brought on by poor diet, and inadequate storage in the liver
modest ETOH can
increase HDL’s
binge drinking can cause
arrhythmias
chronic alcoholics are susceptible to
infection pneumonia
CV risks with chronic ETOH
HTN
anemia
dilated cardiomyopathy
ETOH levels in the fetus reflect
maternal blood levels
does ETOH cross placenta
hell yeah mane
charcteristics of FAS
microcephaly poor coordination intrauterine growth retardation flattened face *1st trimester is mose devastating due to organogenesis
How to deal with intoxicated pt.
- monitor vital signs and airway patency
- thiamine (prevent WK)
- then dextrose (compensate for hypoglycemia)
- fix electrolyte imbalances
why thimaine before dextrose
dextrose can exacerbate WK syndrome
How to deal with withdrawal pt.
BNZo to control withdrawal symptoms
-thiamine (b1)
-correct electrolyte issues
`
symptoms of ETOH withdrawal
DT’s, seizures, n/v, diarrhea, arrhythmias, insomnia, tremor
preferred BNZo for withdrawal
long acting diazepam
*lorazepam if hepatic function impaired
acetominiphen toxicity with ETOH is an example of
Pharmacodynamic intercation
drug on body
increses toxicity of Acetominiphen
disulfiram -like effects
anything that causes build up of acetaldehyde
- doesnt refer to chronic alcoholism tx.
- dont take alcohol with these drugs
3 drugs for tx of alcoholism
- disulfiram–>acetaldehyde antagonist
- Naltrexone–> opiate receptor antagonist
- acamprosate–> gaba agonist
Both methanol and ethylene glycol are broken down initially by
alcohol dehydrogenase
ethylene glycol toxicity
acidosis
nephrotoxicity
methanol toxicity
severe acidosis
retinal damage
drugs to prevent conversion of methanol/ethylene glycol to toxic intermediates
- fomepizole–> alcohol dehydrogenase antagonist
- ethanol–> competitive inihibitor for alcohol dehydrogenase(want a BAL of 100 mg/dL
* greater renal elimination