E1- Alcoholism Flashcards
Alcohol is metabolized by ___ into ___.
Why is alcohol metabolism slower in women?
Alcohol dehydrogenase (ADH) into acetaldehyde
Women have lower levels of Alcohol dehydrogenase
Acetaldehyde is oxidized by ___ into ___.
What does this reaction require?
Aldehyde dehydrogenase (ALDH) into acetate
NAD+
What type of kinetics is alcohol metabolism?
ZERO order kinetics
rate is independent of c oncetration
How does chronic alcoholism lead to pharmacokinetic tolerance?
Ethanol induces CYP2E1 to increase metabolism
How does chronic alcoholism lead to pharmacodynamic tolerance?
Down-regulation of GABA receptors and up-regulation of NMDA receptors
What occur in people with a ALDH deficiency?
Acetaldehyde (toxic alcohol metabolite) accumulates
-Common in those of Asian descent
What is the MOA of alcohol? (2)
- Binds to GABA receptor to increase Cl- influx and enhance inhibitory GABA transmission
- Increases DA in mesolimbic pathway
What is the CNS effect of alcohol at low concentrations?
Disinhibitory, decreased anxiety, mild euphoria, confidence increases
What is the CNS effect of alcohol at high concentrations?
Impaired motor function/judgement speech slurs, depressant/sedative, anterograde amnesia (due to blockade of NMDA receptors)
What are the effects of alcohol?
CNS
Vasodilator (hypothermia)
Depress myocardial contractility
Decreases antidiuretic hormone
What can be used to treat alcohol induced seizures?
Lorazepam (BZ)
Phenytoin (anticonvulsant)
What is paralysis of eye muscles, ataxia, confusion, coma, and death due to thiamine deficiency?chronic disabling memory loss
Wernicke-Korsakoff syndrome
What is chronic disabling memory loss that can occur from chronic alcohol abuse?
Korsakoff’s psychosis:
What are some effects of chronic alcohol abuse?
Gastritis, pancreatitis, liver disease, liver cancer Wernicke-Korsakoff syndrome Korsakoff’s psychosis Peripheral neuropathy Cardiomyopathy Arrhythmias HTN Folate and thiamine deficiency
What are some effects of fetal alcohol syndrome?
Microcephaly Mental retardation Poor coordination Flattened face Joint abnormalities Heart defects Impaired immune system
What are alcohol and drug interactions?
Acetaminophen Phenytoin Hypoglycemics Benzodiazepines Barbiturates Phenothiazines TCAs
What drugs can be used to treat alcoholism? (4)
Naltrexone
Acamprosate
Disulfiram
Topiramate
What is the MOA of Naltrexone?
Opioid receptor antagonist; blocks the ability of alcohol to stimulate the reward pathway
What is a contraindication of Naltrexone?
Liver damage
What is the MOA of Acamprosate?
Structural analogue of GABA; restores the normal balance of GABA and glutamate
What drug (in the treatment of alcoholism) is excreted by the kidneys? AKA has no liver toxicity
Acamprosate
What is the MOA of Disulfiram?
Inhibits ALDH –> acetaldehyde builds up
effects can be severe, not recommended
What is the MOA of o Topiramate?
Anticonvulsant drug
What drugs can be used to help alcohol withdrawal? (4)
Lorazepam (BZ)
Phenytoin (anticonvulsant)
Diazepam (Valium) Chlordiazepoxide
