Pharm of Ethanol [3]

Question 1

How does fat affect blood alcohol level (BAC)?

Answer 1

Fat contains less water (less alcohol distribution, more alcohol accumulation)

• women have greater body fat % than men
• given same dose of ethanol, women will have higher BAC

Question 2

Major metabolic route of elimination of Ethanol

Minor metabolic route of elimination of Ethanol?

Answer 2

zero-order kinetics
Ethanol → alcohol dehydrogenase → acetaldehyde

First-order kinetics
Ethanol → mixed fxn oxidase (P450) → acetaldehyde

Both take place in the liver (90-98%)

Question 3

inhibitor of aldehyde dehydrogenase

Answer 3

disulfiram (antabuse)

• increase acetaldehyde: nausea, vomiting, respiratory/cardio collapse, convulsions
• protection against alcoholism

Question 4

what compound builds up in asians?

Answer 4

Acetaldehyde

• due to increased activity of alcohol dehydrogenase
• or due to high Km (low affinity) of aldehyde dehydrogenase (cant break down acetaldehyde → acetic acid)

Question 5

How are these levels affected with hepatic metabolism of ethanol and what can that lead to?
NADH
Blood lactate
MG2+ excretion
Acetyl CoA
Uric acid excretion

Answer 5

↑ NADH → hypoglycemia (↓gluconeogenesis from Krebs)
↑ Blood lactate → acidosis
↑ MG2+ excretion → convulsions
↑ Acetyl CoA → fatty liver (↑ fat synth + ↓ fat breakdown)
↓ Uric acid excretion →

Question 6

DWAI

DUI

Answer 6

DWAI: impaired driving ability (0.05-0.08)
DUI: (0.08-0.2)

Question 7

How does Ethanol affect sleep?

Answer 7

suppression of stage IV REM (best sleep)
but then you rebound with withdrawal (nightmares)
- similar to barbiturates

Question 8

Alcohol intoxication at lethal doses most closely resembles intoxication with which class of abused drug?

Answer 8

barbiturates (pentobarbital)

• great CNS depression, low safety margin
• sleep effects
• anticonvulsant initially (then ppt seizures)

Question 9

Are BDZ or barbs gen used to suppress -OH withdrawal?

Answer 9

BDZ (cross dependence) - sedative hypnotics
GAs
(a2 adrenergic agonists - clonidine)

Question 10

name that disease/psychosis

• confusion
• diplopia
• nystagmus
• ataxia
• periph neuropathy

Answer 10

wernicke’s disease

eth toxicity, malnutrition

Question 11

name that disease/psychosis

• disorientation
• amnesia
• confabulations

Answer 11

Korsakoff’s psychosis

eth toxicity, malnutrition

Question 12

Signs with early/acute Eth withdrawal (minor)

what about late (major withdrawal)?

Answer 12

Tremor
Anxiety
Agitation
Insomnia
Restlessness (NOT somnolence)

Disorientation
Confusion
Disordered sensory perception

Question 13

DDI for Ethanol

Answer 13

faster CYP2E1 metabolism

• reduced drug effect
• Potentiate acetaminophen toxicity

Question 14

How are BDZ and a2 adrenergic agonists good against alcohol withdrawal syndromes?

Answer 14

BDZ: action at GABA PREVENTS emergence of CNS HYPEREXCITABILITY following withdrawal of alcohol

a2 agonist (clonidine) effective for autonomic hyperactivity

Question 15

Which drugs reduce alcohol consumption?

Answer 15

Disulfiram - alcohol sensitizing drug
Naltrexone - opioid antagonist (block u reinforcement)
- turns wine into water
Acamprosate - NMDA R blocker (↓ craving)