Alcohol Drugs Flashcards
Toxicants
Ethanol
Methanol
Ethylene Glycol
Antidotes
Disulfiram
Fomepizole
Ethanol
Drugs for Ethanol Withdrwal
Diazepam
Thiamine (Vitamin B1)
Drugs for chronic Alcoholics
Naltrexone
Acamprosate
Acute methanol or ethylene glycol intoxication treatment
ethanol or fomepizole
Several drugs are available to treat alcohol dependency, either through changes in
ethanol metabolism or through effects in the ventral tegmental area (VTA) and nucleus accumbens (NA), areas of the brain involved in the response to addictive drugs.
The enzymes involved in conversion of alcohol are
alcohol dehydrogenase and aldehyde dehydrogenase
The metabolism of ethanol, like that of phenytoin and high-‐dose aspirin is a
0-‐order process, in other words the enzymes involved in metabolism are saturated and performing at maximum capacity.
Disulfiram is used to encourage abstinence from
alcohol by preventing the metabolism of acetaldehyde, thus leading to the accumulation of this normally transient intermediate.
Accumulation of acetaldehyde gives rise to
a feeling of nausea and a flushing reaction of the skin.
Although cytochrome P450 is not a major player in the metabolism of ethanol, ethanol is an important inducer of
CYP2E1.
Acetaminophen is normally conjugated with either a
sulfate or to a glucuronide
acetaminophen is converted through a highly reactive intermediate:
NAPQI, is itself rapidly conjugated and detoxified
chronic alcoholics who have induced CYP2E1, there is a dramatically increased rate and extent of conversion to of acetaminophen to
NAPQI.
In chronic alcholoics available stores of conjugate substrate to detoxify acetaminophen reactive intermediate become
depleted and with accumulation of NAPQI in the liver, significant hepatotoxicity occurs.
the antidote in acetaminophen toxicity in alcoholics is
administration of N-‐acetylcysteine which provides fresh conjugate substrate for the reactive intermediate to be safely detoxified.
BAL (mg/dL) <50
Limited muscular incoordination
BAL (mg/dL) 50-100
Pronounced incoordination
BAL (mg/dL) 100-150
Mood & personality changes; intoxication over the legal limit in most states
BAL (mg/dL) 150-400
Nausa, vomiting, marked ataxia, amnesia, dysarthria
BAL (mg/dL) >400
Coma, respiratory insufficiency & death
Impact of Alcohol on GABA A
GABA release and increase receptor density
Impact of Alcohol on NMDA
Inhibition of postsynaptic NMDA receptors; with chronic use, up regulation.
Impact of Alcohol on Dopamine
Increase synaptic dopamine, increase effects on ventral tegamentum/nucleus accumbens reward
Impact of Alcohol on ACTH
Increase CNS and blood levels of ACTH
Impact of Alcohol on Opoid
Release of B endorphins, activation of mu receptors
Impact of Alcohol on 5-HT
Increase in 5-HT synaptic space
Impact of Alcohol on Cannabinoid
Increase CB1 activity leading to changes in DA, GABA, glutamate activity
Alcohols effects on CV & smooth muscles
CV depressant , relaxes vascular smooth muscle causing vasodilation, possible hypothermia, and increased gastric blood flow. Relaxes uterine smooth muscle.
Since alcohol does NOT distribute into
adipose tissue, those with a large BMI would tend to experience higher BAL as alcohol would be excluded from that tissue compartment.
