Alcohol

Question 1

Ethanol metabolism

Answer 1

ADH = <10%, in liver and gut, 7-10g/hr
MEOS = >10%, CYP/p450

Question 2

What is acetylaldehyde?

Answer 2

ADH/MEOS breaks ethanol down into it

Build up leads to N/V, headache and hypotension

Question 3

Acute ethanol drug intxns

Answer 3

ALDH inhibit by hypoglycemics and Flagyl

Competition at p450 with TCA, H1 antihistamines, narcotics, and benzos leads to CNS depression

Question 4

Chronic alcohol interactions

Answer 4

Induction of CYPs increases likelihood of secondary drug metab
Acetaminophen hepatotoxicity even at low dose

Question 5

How do you treat acetaminophen hepatotoxicity?

Answer 5

N-acetylcysteine

Neutralizes reactive intermediates

Question 6

How much alcohol is 1% BAC

Answer 6

1 g/dL

Question 7

How much alcohol is in a typical drink?

Answer 7

15 g ethanol
12 oz beer
4 oz wine
1.5 oz shot

Question 8

Volume of distribution of alcohol

Answer 8

Men = 0.7 L/kg
women = 0.63 L/kg

Question 9

Mechanisms of CNS effects

Answer 9

Enhance GABA
Inhibit glutamate at NMDA
Chronic: inc synaptic dopamine and endogenous opioids in NA and VTA

Question 10

Metabolic tolerance to alcohol

Answer 10

Pharmacokinetic

Induction of MEOS/CYPs leads to more rapid break down of alcohol

Question 11

Functional tolerance to alcohol

Answer 11

Pharmacodynamic
Reduction in CNS sensitivity to ethanol d/t changes in neurons
Downreg of GABA, upreg of NMDA

Question 12

Tx of acute intoxication

Answer 12

Maintain vitals
Prevent vomit aspiration
IV dextrose
Thiamine

Question 13

Treatment of mild w/d

Answer 13

Central clonidine (a2 agonist)
Peripheral propanolol (B antagonist) 
Decrease sympathetic outflow

Question 14

Tx of severe w/d

Answer 14

Diazepam and thiamine

Question 15

Disulfiram

Answer 15

Alcohol aversion therapy
Inhibits ALDH leading to acetylaldehyde build up upon alcohol consumption
AE: hepatotoxic, resp depression/CV collapse/convulsion if alcohol consumed binge

Question 16

Naltrexone

Answer 16

Anti-craving therapy
MOA: inhibits mu opioid receptors in VTA to reduce rewarding effects
AE: hepatotoxic at high dose
WILL CAUSE SEVERE W/D IN OPIOID USERS

Question 17

Acamprosate/topiramate

Answer 17

Anti-craving
Inc GABA, inhib glutamate
Combined with disulfiram is more effective

Question 18

Why should you do the nalaxone challenge before admin naltrexone?

Answer 18

Nalaxone is a short acting antagonist - will cause w/d effects that are less severe than if you give naltrexone to an opioid abuser

Question 19

Toxic effects of methanol

Answer 19

Acidosis

Retinal damage

Question 20

Toxic effects of ethylene glycol

Answer 20

Acidosis

Nephrotoxicity –> oxalate crystals

Question 21

Tx for methanol or ethylene glycol poisoning

Answer 21

Ethanol or fomepizole
Bind to ADH which prevents metab of toxics
Bicarb, hemodialysis