Alcohol Use and Abuse Flashcards
What are some alternatives to ethanol (i.e. for alcoholics who cant find beer)?
metahnol or ethylene glycol (but remember these produce toxic metabolites and preventation of their metabolism is accomplished by giving ethanol or fomepizole)
How migh alcohol withdrawal present?
vitamin deficiency (need to thiamine usually)
agitation (need for benzos)
Again, acute methanol or ethylene glycol intoxication is best tx with what?
ethanol or fomepizole
What are some options for tx alcohol dependency?
Disulfram
Naltrexone
Acamprosate
How is ethanol metabolized?
Occurs primarily in the liver where it is first emtabolized to acetaldehyde and subsequently to acetate via alcohol dehydrogenase and aldehyde dehydrogenase, respectively.
T or F. The metabolism of alcohol is a zero order kinetic phenomenon
T. Like phenyotin and aspirin
Normally, there is very little CYP involvement in ethanol metabolism, except:
In the case of ethanol overdose in which it may become neccessitated
How does disulfram work?
It encourages abstinence by preventing the metabolism of acetaldehyde, thus leading to accumulation of this normally transient intermediate, which causes a feeling nausea and flushing
Usually accumulation of acetaldehyde causes a sickening feeling. When is this effect different?
Some alcoholics find the effects of acetaldehyde pleasurable (especially Asians with a ALDH2*1/2*2 heterozygosity; may explain alcoholism prevalance among Native Americans) in which its effects are still unpleasant in the periphery but pleasurable in the VTA where it promotes dopamine release
Although CYP450 is not a major player in the metabolism of ethanol, ethanol is an important inducer of _____
CYP2E1 (so alcohol can affect the metabolism of concurrent drugs)
What is a major DDI with ethanol due to its inducing of CYP2E1?
Tylenol (acetaminophen) b/c Tylenol is normally conjugated with either a sulfate or to a glucuronide, but is more commonly metabolized to NAPQI in the presence of alcohol which depletes glutathionine
What is the antidote to acetaminophen OD?
N-acetylcysteine
Unlike most drugs, ethanol does not act upon one specific receptor, but many. Describe some of the NTM effects
1) Increases GABA release and receptor density
2) Inhibits postsynaptic NMDA receptors (upregulation with chronic use)
3) Increases synaptic DA and its effects on the ventral tegmentum/nucleus accumbens
4) Increases CNS ACTH and opiods
5) Release of serotonin
6) Inhibition of glutamate release
How does chronic alcohol consumption affect the body?
Dont know what causes the peripheral neuropathy
Thiamine deficiency in alcoholics can lead to what?
Wernicke Encephalopathy with its classic triad of ocular motor abnormalities, cerebellar dysfunction, and an altered mental state (confabulations)
How does fetl alcohol syndrome arise?
Ethanol can easily pass through the placenta and fetal levels closely reflect that of the maternal circulation. Fetuses have a general inability to metabolize ethanol and the earlier the exposure occurs, the more severe the outcome. (I.e. if exposure occurs in the 3rd trimester, might only see subtle neurologic deficits, but organogenesis has already largely completed)
How does FAS present?
What drugs produce disulfram-like effects?
Sulfonylureas, cefotetan, ketoconazole, and procarbazine
