alcohol (ethanol and methanol) are metabolized by what 3 things
- ADH: alcohol dehydrogenase
- MEOS
- CYP2E1
alcohol metabolism follows what order kinetics? Is rate dependent on concentration?
- zero order
- 10 g/ hr
- rate is independent of concentration
describe the pathway of metabolism of alcohol
- Alcohol (ethanol and methanol) is metabolized in the GI tract and liver by alcohol dehydrogenase (ADH) to acetaldehyde.
- Acetaldehyde is oxidized by aldehyde dehydrogenase to acetic acid.
- Oxidation requires a cofactor, NAD+
- Since the available NAD+ is used for alcohol metabolism, there is less available for other enzymes requiring NAD+
- Lactate increases, the TCA cycle is inhibited, and acetyl-CoA accumulates.
- This supports fatty acid synthesis, storage and accumulation of triglycerides, formation of ketones and contributes to lactic acidosis.
chronic consumption of alcohol induces
- Microsomal-ethanol oxidizing system (MEOS) (CYP450s)
- CYP2E1
- thus increasing metabolism. Increased metabolism may account for the greater tolerance of chronic drinkers
chronic consumption of alcohol induces CYP2E1, this increases toxicity to what drug
acetaminophen
- therapeutic amounts of acetaminophen can cause hepatotoxicity in alcoholics, increasing conversion of acetaminophen to a toxic metabolite
Aldehyde dehydrogenase deficiency is commonly seen in what patient population? What is the effect?
- acetaldehyde can accumulate in people with a mutation in ADH, especially those of Asian descent, leading to facial flushing, headache and nausea when alcohol is consumed.
do women or men have lower levels of ADH
women
MOA of Disulfiram
acts by inhibiting aldehyde dehydrogenase, producing very unpleasant and possibly dangerous effects with alcohol
MOA of Fomepizole
inhibits alcohol dehydrogenase
Tolerance in chronic drinkers is due to down regulation of receptors and up-regulation of receptors. What does this lead to when a chronic drinker stops drinking?
- GABA
- NMDA
- severe withdrawl
In chronic alcoholic drinkers, cross tolerance is seen with
- barbiturates
- benzodiazepines
Alcohol has what effect on CNS
CNS depressant
alcohol binds to what receptor? Binding increases influx of . What is the overall effect?
- GABAA receptor
- increases Cl- influx
- enhance inhibitory GABA transmission
Alcohol inhibits the effect of glutamate on the . These receptors are involved in learning and memory, and generation of seizure activity.
NMDA receptor
Alcohol increases in the mesolimbic pathway
dopamine
What are the effects of alcohol on the CNS at low concentrations and at increased doses
- low concentration: alcohol may have some stimulant-like effect. It inhibits inhibitory pathways (disinhibition). Memory, concentration, and rational thought are affected. Confidence, mood
- Increased dose: inhibit excitatory pathways -> motor function and judgment impaired, speech clurs, ataxia
anterograde amnesia (blackouts) occur due to blockage of what receptors
NMDA receptors
effects of alcohol on smooth muscle
- Ethanol is a vasodilator, and large amounts can cause hypothermia due to vasodilation
- Ethanol also relaxes the uterus, and has been used intravenously to prevent premature labor.
effects of alcohol on the heart
depression of myocardial activity
effects of alcohol on the kidney
- decreases antidiuretic hormone thus producing a diuretic effect
Treatment of severe intoxication includes what two main goals
- management of respiratory depression
- preventing aspiration of vomitus.
hangovers are due to
- buildup of acetaldehyde
- dehydration
- withdrawal
What medications can be given if seizures occur during acute alcohol toxicity
- Lorazepam (ativan): benzodiazepine
- Phenytoin (dilantin): anticonvulsant
Lorazepam (ativan) falls in what drug class
benzodiazapine
