Flashcards in Alcohol: use and abuse Deck (47):
alcohol dehydrogenase is inhibited by which drug?
fomepizole (drug that is used in the treatment of acute ethanol or ethylene glycol intoxication)
inhibits aldehyde dehydrogenase leading to the buildup of acetaldehyde which quickly gives rise to a feeling of nausea and vomiting
explain how some alcoholics find acetaldehyde pleasurable
appears to provide dual action
-unpleasant in the periphery
-pleasure in the VTA where it promotes DA release
-condenses w/ DA to make salsolinol (strongly reinforcing agent)
asians with what heterozygosity experience significantly more positive feelings after alcohol intoxication?
-Allele assoc. w/ lower prev. of abuse & alcoholism
-acetaldehyde may explain alcoholism prevalence among Native americans
which CYP enzyme is induced with extensive alcohol abuse?
with alcoholisms CYP2E1 is induced which leads to the accumulation of what highly toxic metabolic intermediate of acetaminophen metabolism?
what molecule is needed to converted NAPQI into Cysteine & mercapturic acid conjugates?
what are the physiologic effects of a pt who has a BAL of 15-400 mg/dL?
N/V, ataxia, amnesia, dysarthria
what effect does alcohol have on GABA-A?
increased GABA release, increased receptor density
what effect does alcohol have on NMDA?
inhibition of postsynaptic NMDA receptors; w/ chronic use, up-regulation
what effect does alcohol have on dopamine?
increases synaptic DA, increased effects on ventral tegmentum (VTA) & nucleus accumbens (NA) reward
what effects do alchol have on ACTH?
increase CNS & blood levels of ACTH
what effects do alcohol have on opioids?
release of beta-endorphins, activation of mu receptors
what effect does alcohol have on 5-HT?
increased 5-HT in the synaptic space
what effects do alcohol have on cannabinoid?
increased CB1 activity--> changes in DA, GABA, glutamate activity
what are the effects of alcohol on CV, smooth muscle and uterine smooth muscle?
Relaxes smooth muscle (vasodilation, increased gastric bloodflow)
Relaxes uterine smooth muscle
which gender has a higher BAL typically?
why do women typically have a higher BAL than men?
more body fat
what is the relationship b/w BMI and BAL?
higher BMI = more body fat = small Vd = higher BAL
what is the most significant component to adaptation with alcohol?
behavioral and neural adaptation
what are the chronic effects of ethanol on the liver?
decreases gluconeogenesis (hypoglycemia)
fatty liver-hepatitis, cirrhosis & failure
explain how chronic alcohol use can cause hypoglycemia
alcohol increases the NADH/NAD ratio in the liver, which (via normal ethanol metabolism), causing pyruvate --->lactate and OAA-->malate; therefore this inhibits gluconeogensis
explain how chronic alcohol use can cause fatty liver?
alcohol use depletes OAA which shuts down the TCA cycle and this causes acetyl-coA to get shunted into ketone production.
Breakdown of excess malate increases NADPH and thus this increases fatty acid synthesis
what are the chronic effects of alcohol on the GI system?
bleeding, scarring causing/exacerbating nutritional deficiencies
what are the chronic effects of alcohol on the CNS?
peripheral neuropathy (MC)
Wernicke-korsakoff syndrome (ataxia, confusion, ocular muscle paralysis, treat with thiamine)
what is the Wernicke-Korsakoff syndrome classic triad?
Treat with thiamine
what are the chronic effects of alcohol on the endocrine system?
gynecomastia & testicular atrophy secondary to steroid insufficiency
what are some of the reasons why alcoholics have a thiamine deficiency?
decreased thiamine in diet
decreased thiamine absorption in GI tract
decreased thiamine storage in liver
what are the chronic effects of alcohol on the CV system?
HTN, anemia, dilated cardiomyopathy
arrhythmias w/ binge drinking
Modest alcohol intake increases HDL & may protect against CHD
what are the chronic effects of alcohol in regards to cancer?
higher incidence of GI cancer (e.g. esophageal squamous cell carcinoma=upper esophagus)
what are the effects of chronic alcohol use on the immune system?
extra inflammation in liver & pancreas, but reduced immune response in other tissues
-chronic alcoholics susceptible to infectious pneumonia
what are some of the features of fetal alcohol syndrome?
minor joint anomalies
the fetal alcohol levels reflect the ________
maternal alcohol levels
how do you treat a pt intoxicated w/ alcohol in the ER ?
what are the features of alcohol withdrawal?
insomnia, tremor, anxiety
DTs, and rarely seizures
how do you treat alcohol withdrawal?
if an alcoholic pt who is withdrawing also has hepatic dysfunction, which BNZ can you give him?
lorazepam (b/c it's only processed by glucuronidation-phase II)
name all the drugs you can think of that have disulfiram-like effects?
how is naltrexone used in alcoholism?
mu (OP-3) Opioid antagonist; decreases the high you get with drinking
how is acamprosate used in alcoholism?
weak NMDA antagonist, activates GABA-A receptors; may decreased mild protracted abstinence syndromes with decreased feeling of need for alcohol
alcohol indirectly activates which pathway in the brain?
corticomesolimbic dopaminergic pathway, which goes from VTA to the NA (important in the rewarding effects of many drugs)
which enzyme metabolize both ethylene glycol and methanol to other toxic metabolites?
how do you treat ethylene glycol/methanol intoxication?
1. treat with fomepizole (inhibits Alcohol DH) and allows renal elimination
2. treat with ethanol and keep at 100 mg/dL to ensure enzyme saturation
what is the result of ethylene glycol poisoning?
what is the result of methanol poisoning?
severe acidosis, retinal damage
how is fomepizole administered?