Toxicology of Alcohol

Question 1

ADH pathway

Answer 1

• located mainly in the liver
• activated at lower concentrations of alcohol
• polymorphism especially in Asians

Question 2

MEOS pathway

Answer 2

• consists of P450, 3A4 most important isozyme
• inducible in chronic intoxication
• NAD+ independent, higher threshold than ADH

Question 3

MOA of fomepizole

Answer 3

• inhibits ADH

Question 4

MOA of disulfiram

Answer 4

• inhibits aldehyde dehydrogenase

Question 5

drugs that potentiate disulfirams effects

Answer 5

• metronidazole
• cefotetan
• trimethoprim

Question 6

GABA-A drugs and the effects of alchol

Answer 6

• GABA-A mimetic (benzos, barbiturates) exacerbate the effects of ethanol
• GABA-A antagonists decreases the effects

Question 7

ethanol effect on NMDA receptors

Answer 7

• decreases the ability of glutamate to open the cation channel associated the the NMDA receptor

Question 8

symptoms of mild alcohol withdrawal

Answer 8

• tremors
• anxiety
• insomnia
• starts 6-8 hours after consumption stops

Question 9

symptoms of severe alcohol withdrawal

Answer 9

• visual hallucinations
• total disorientations
• marked abnormality of vital signs

Question 10

treatment of mild withdrawal cases

Answer 10

• PO4, K, an Mg balance should be restored as soon as possible
• thiamine therapy is initiated in all cases

Question 11

treatment of severe withdrawal cases

Answer 11

• thiamine therapy
• hemodialysis and drug therapy
• long acting sedative hypnotic is administered and then tapered off (benzos are preferred)
• short acting benzos (lorazepam and oxazepam) are recommended in patients with liver problems

Question 12

three available drug therapies for alcoholism

Answer 12

• naltrexone
• acamprosate
• disulfiram

Question 13

naltrexone

Answer 13

• mu antagonist that reduces cravings and reduces relapses to either drinking or alcohol dependence
• should not be administered concurrently with disulfiram because of risk of hepatic toxicity
• patients must be opioid free before taking naltrexone

Question 14

acamprosate

Answer 14

• weak NMDA receptor antagonist

- C.I. in patients with serious renal impairment

Question 15

disulfiram

Answer 15

• causes severe discomfort in drinkers

Question 16

metabolism of methanol

Answer 16

• methanol to formaldehyde to formate

Question 17

symptoms of methanol poisoning

Answer 17

• visual disturbances (blurred vision with clear sensorium is a giveaway)
• metabolic acidosis
• ## smell of formaldehyde on the breath and in urine

Question 18

lab finds in methanol poisoning

Answer 18

• metabolic acidosis with elevated anion gap and osmolal gap

Question 19

treatment of methanol poisoning

Answer 19

• suppression of metabolism (FA may increase metabolism of formate)
• hemodialysis
• alkalinization
• ethanol IV to compete for ADH to reduce formaldehyde buildup

Question 20

indications of fomeprizole

Answer 20

• methanol and ethylene glycol poisoning

Question 21

three stages of ethylene glycol overdose

Answer 21

• transient CNS excitation followed by CNS depression within the first few hours
• severe metabolic acidosis
• deposition of oxalate in the renal tubules leads to delayed renal insufficiency (CK, BUN, K all increase)

Question 22

lab findings of ethylene glycol poisoning

Answer 22

• acidosis with anion gap, osmolal gap and oxalate cystals in the urine without visual symptoms

Question 23

treatment of ethylene glycol

Answer 23

• hemodialysis and ethanol IV