Alcohol Flashcards
What is a typical dose of alcohol?
How much will this increase the BAC of a 70kg human?
14grams, or “12oz beer, 5oz wine, 1.5oz hard liquor”
30mg/dL, or BAC +0.03
Where is alcohol absorbed?
The entire GI tract–this is one of the rare compounds that may be absorbed through the stomach.
What is alcohol’s distribution, relative to body weight?
Since alcohol distributes in total body water, it should be 60-100% of total body weight.
Describe the sequential metabolism of ethanol to acetate. Include cofactors.
Which step is usually rate-limiting?
EtOH + NAD+/NADP+ > Acetaldehyde + NAD+ > Acetic acid.
The enzymes are ADH/CYP2E1 and Aldehyde Dehydrogenase.
ADH is usually the rate-limiting enzyme.
What drugs have zero-order metabolism?
Phenytoin
Ethanol (~10g/hr)
Aspirin
Why does alcohol consumption promote steatohepatitis? Cirrhosis?
Fatty deposits in liver accumulate in response to the increased levels of NADH.
Cirrhosis is probably due to liver inflammation due to increased acetaldehyde.
By what two mechanisms to chronic alcoholics tolerate ethanol?
Metabolically (induction of CYP2E1)
Adaptive neuronal changes (upregulate excitatory transmission)
What are the effects of ethanol on metabolism?
Ethanol downregulates gluconeogenesis and fatty acid catabolism, and can induce hypoglycemia and ketoacidosis.
Ethanol itself is quite energy-rich; 7kcal/g (more like a lipid than a carbohydrate)
How does ethanol cause CNS depression?
Activation of GABAA chloride channels.
What are some potential consequences of thiamine deficiency?
How does this deficiency occur?
Thiamine defiency causes profound CNS effects–atrophy, Wernicke’s encephalopathy, Korsakoff’s psychosis.
Thiamine absorption is blocked by ethanol, and chronic alcoholics are less likely to get a balanced diet (see also: pellagra)
At what BAC level is coma observed? About how many drinks is this?
What is the treatment for acute alcohol toxicity?
.40, around 12 drinks if taken at once.
Support of respiration and avoiding aspiration of vomit, as well as correcting for concurrent metabolic disorder.
Don’t stomach-pump or induce emesis–ethanol is absorbed too quickly. No direct antidote?
What are the symptoms of ethanol withdrawal?
Why might one administer diazepam to these patients? Atenolol?
Cravings, agitation, insomnia, sweating, tachycardia, and sometimes seizures.
Diazepam will mimic the CNS depression, but can be controllably weaned. Atenolol is used to prevent the tachycardias.
Naltrexone
What is the mechanism of action?
What are its indications?
Naltrexone
Antagonism of the mu opioid receptor.
In conjunction with psychosocial therapy, help recovering alcoholics from cravings & relapse.
Acamprosate
What is the mechanism of action?
What are its indications?
Acamprosate
Agonism of the GABAA receptor (same as ethanol)
It is administered to recovering alcoholics to “normalize dysregulated neurotransmission”.
Disulfram
What is the mechanism of action?
What are its indications?
Disulfram
Inhibition of aldehyde dehydrogenase–causes accumulation of acetaldehyde after drinking ethanol.
When given to alcoholics, creates unpleasant experience after drinking (aversion therapy).
