pharm of ETOH

Question 1

Describe the absorption, distribution, and metabolism of ethanol and their relationship to the blood alcohol concentration (BAC).

Answer 1

absorption-Heavy meal can decrease peak concentration by 30%
distribution-distributed in TBW, women Given same g/kg dose of ethanol as man of equal weight woman will have a higher BAC
metabolism- first broken down by alcohol dehydrogenase in liver, then aldehyde dehydrogenase.

Question 2

Describe the site of action of Antabuse„¥ (disulfiram) and the aversive actions of acetaldehyde.

Answer 2

Antabuse acts on aldehyde dehydrogenase, leads to build up acetaldehyde which is like poison and makes you feel terrible

Question 3

Describe the role of NADH in alcohol metabolism and the metabolic disruptions associated with alcohol abuse
5 things:

Answer 3

increase levels of NADH, decrease Krebs activity->gluconeogenesis->hypoglycemia

increase blood lactate-> acidosis, behavioral disturbances

increased Mg++ excretion-> can lead to convulsions

increase Acetyl CoA -> increase F.A. synthesis + decrease fat breakdown -> fatty liver

decrease uric acid excretion –>may precipitate gout attacks

Question 4

Describe the effects of ethanol on: the CNS (esp. the mechanism of acute neuronal actions), liver, kidney, GI tract,

Answer 4

Low-moderate dose (0.05-0.250 g/dL) increase GABA plus decrease Glutamate neuronal function
suppression of stage IV-REM
induces vomiting
hepatitis, fatty liver, pancreatitis, esophageal varices, CHF hypothermia, kidney diuresis due to decrease ADH
Wernicke’s Disease
Korsakoff’s psychosis -wernickes + Disorientation, amnesia, confabulations
Cerebral atrophy- Frontal lobe degeneration personality disintegration dementia - irreversible
Cerebellar atrophy- Irreversible ataxia

Question 5

Explain tolerance to, dependence on, and withdrawal from ethanol

Answer 5

tolarance builds quick and u lose it quick, dependence is high, withdrawal is dangerous, seizure, delerium tremens, visual hallucinations, anxiety, insomnia tremor

Question 6

List the major drug-drug interactions associated with alcohol use.

Answer 6

Additive effects with all CNS depressants (acute)
Cross-tolerance to sedative-hypnotic drugs and general anesthetics (chronic use)
Can promote GI bleeding if taken with aspirin
Increase risk of hepatotoxicity with acetaminophen
Disulfiram-like symptoms with metronidazole

Question 7

Describe the management of acute alcohol intoxication and withdrawal.

Answer 7

Support of respiration
Administration of IV fluids - glucose, thiamine, and electrolytes (K+ and Mg++)
No specific antidote available

Benzodiazepines-act via principle of cross-dependence
α2 adrenergic agonists (clonidine)-Effective for signs of autonomic hyperactivity

Question 8

(Fetal Alcohol Syndrome).

Answer 8

1 in 3 in heavy drinkers
Criteria for FAS
Prenatal or postnatal growth retardation
AND altered morphogenesis (especially facial dysmorphology)

AND CNS involvement – developmental delay, learning disabilities

Question 9

Alcohol avoidance tx

Answer 9

Alcohol sensitizing drugs (Disulfiram [Antabuse])
-Little evidence of clinical efficacy
Opioid antagonists (Naltrexone)
NMDA receptor drugs (Acamprosate [Camprasal])
-Some reduction in alcohol craving and relapse rates in combination with psychotherapy
-Weak block of NMDA receptor function