Flashcards in Alcohol Deck (18):
What 3 things influence the rate of alcohol absorption?
1. Ethanol concentration.
2. Rate of consumption.
3. Gastric contents.
What is the first major metabolite of alcohol?
Activates GABA receptor ligand-gated Cl- channels (suppress neuronal transmission, help maintain resting membrane potential in some neurons), and inhibits NMDA receptor ligand-gated cation channel (affects cognitive function, learning, memory).
Effects of chronic alcoholism:
1. Liver disease (due to fatty liver, Hep C, cirrhosis (due to necrosis and chronic inflammation)).
2. GI pathologies (chronic gastritis, malabsorption of vitamins).
3. Neurotoxicity due to thiamine deficiency. Cerebellar atrophy.
Consequences of alcohol tolerance:
Chronic ethanol leads to CNS depression leads to up-regulation of excitatory neurons.
Alcohol metabolic tolerance MOA:
Upregulation of CYP2E1.
Effects of alcohol on acetaminophen metabolism:
More likely to cause liver toxicity due to to either upregulation of CYP2E1 in alcoholics or inhibition of CYP2E1 along with decreased glutathione in acute toxicity.
Major concern for alcohol withdrawal:
Fetal alcohol syndrome:
Failure to thrive, microcephaly, facial abnormalities. Is a direct result of ethanol or acetaldehyde on embryonic cellular proliferation.
Signs of alcohol withdrawal syndrome & goal of treatment:
-Craving, agitation, anxiety, insomnia, seizures, mood swings, sweating, tachycardia.
-Goal is to prevent seizures, delirium, arrhythmias.
2 specifics on alcohol dehydrogenase pathway:
1. Is RLS in alcohol metabolism.
2. Requires NAD+, zero-order kinetics.
2 major consequences of ethanol metabolism:
1. Increased NADH results in inhibition of TCA cycle and decreased oxidation of fats (basis behind fatty liver).
2. Increased acetaldehyde leads to a generation of protein adducts, decreased glutathione, inhibition of microtubules.
Microsomal ethanol oxidizing system:
Induced in alcoholics - requires high concentrations of alcohol to kick in. Influences metabolism of other drugs because of increased levels of CYP2E1. Uses NADPH as a co-factor.
-Mitochondrial enzyme; oxidizes acetaldehyde to acetate.
-Genetic polymorphisms (in a lot of Asian populations) contribute to accumulation of acetaldehyde.
Inhibitor of aldehyde dehydrogenase. Aversion therapy.
Can be used as "substitutes" of alcohol for therapy:
Benzodiazepines, Diazepam, Chlordiazepoxide.
Naltrexone MOA and use:
Opioid receptor antagonist. Reduces the urge to drink. Best with psychosocial therapy.