Alcohol DSA (Kruse)

Question 1

Peak blood levels of EtOh reached within __ when stomach is empty.

Absorption occurs more rapidly from what GI region?

Extensive 1st pass metabolism by what enzyme?

Answer 1

30 mins

more rapidly from SI rather than stomach

Gastric and liver ADH

Question 2

Metabolism/what order of kinetics does etoh follow?

Answer 2

zero order kinetics

Question 3

what is etoh mostly metabolized to?

Answer 3

acetate (90-98%) owing to ADH and ALDH

Question 4

what genes appear to protect against alcoholism? susceptibility to alcoholism?

Answer 4

protect=polymorphisms in ADH and ALDH

suceptible=D4 receptor, B1 subunit of GABA-A receptor, Tyrosine hydroxylase

Question 5

__ inhibits gastric ADH and can increase etoh bioavailability

__ inhibts ADH and is used in tx of acute methanol or ethylene glycol posioning

Answer 5

aspirin

fomepizole

Question 6

ALDH is inhibited by __ which is a drug used for tx of alcohol abuse and dependence

Answer 6

Disulfiram

Question 7

genetic polymorphisms in this enzyme seen in some of asian descent and when they drink etoh, develop high levels of acetaldehyde and experience flsuhing, light headedness, palpitations, nausea, hangover symptoms

Answer 7

ALDH

Question 8

chronic etoh consumptions induces CYP__ and can result in enhanced activation of toxins, free radicals, and H2O2

Answer 8

CYP2E1

Question 9

Etoh effect on NMDA receptors?

Etoh effect on GABA receptors

Answer 9

NMDA –> inhibits ability of glutamate to open cation channel of NMDA receptor –> increased CNS depression

GABA –> enhances effects of GABA on GABA-A receptor and leads to increased CNS depression

Question 10

etoh effect on the heart? smooth muscle?

Answer 10

heart–> depression of myocardial contractility; dilated cardiomyopathy and HF in chronic abusers

smooth m. –> vasodilation and smooth m. relaxation caused by metabolite acetaldehyde; if severe, can cause hypothermia caused by vasodilation

Question 11

wernicke-korsakoff syndrome is associated with __ deficiency

Answer 11

thiamine

Question 12

this neurotoxic condition of chronic alcohol abuse is paralysis of external eye muscles, ataxia, and a confused state that can progress to coma and death. Assoc w/thiamine deficiency and tx with thiamine will improve ocular problems, ataxia, and confusion but most are left w/chronic disabiling memory disorder

Answer 12

wernicke-korsakoff syndrome

Question 13

s/s of FAS?

Answer 13

• intrauterine growth restriction
• microcephaly
• poor coordination
• underdevelopment of midfacial region
• minor joint abnormalities

Leading cause of MR and congenital malformations

Question 14

management of acute alcohol intoxication?

Answer 14

• prevent severe resp depression and aspiration of vomit
• glucose=tx metabolic alteration (hypoglycemia and ketosis)
• Thiamine
• Potassium if severe vomitting

Question 15

management of alcohol withdrawal syndrome?

Answer 15

-major pharm objective is prevent seizures, delirium, and arrhythmias; electrolyte rebalancing and thiamine tx

For detox: Long-acting benzo (chlordiazepoxide, clorazepate, or diazepam; Short-acting benzo (lorazepam or oxazepam)

Question 16

primary tx of etoh dependence?

Answer 16

psychosocial therapy

Question 17

Pharmacological tx of etoh dependence?

Answer 17

• Naltrexone=short term, 12 wks
• Acamprosate=weak NMDA receptor antagonist and GABA-A receptor agonist, caution in pts w/kidney disease
• Disulfiram=pt must be highly motivated, not common d/t low compliance

Question 18

Tx of methanol poisoning?

Answer 18

• Resp support
• Suppression of metabolism by ADH (Ethanol or Fomepizole)
• hemodialysis to enhance methanol removal
• alkalinization to counteract metabolic acidosis (bicarb)

-Etoh often used IV as tx

Question 19

Tx for ethylene glycol poisioning?

Answer 19

• Hemodialysis
• Ethanol infusion
• Fomepizole