Alcohols & Drugs for Tx

Question 1

Briefly describe the process that leads to alcoholic cirrhosis.

Answer 1

Decreased gluconeogenesis and NAD depletion –> hypoglycemia, fat accum. in the liver –> cirrhosis

Question 2

What are some major drug classes with which alcohol interacts?

Answer 2

TCAs, H1-antihistamines, narcotics, and anticonvulsants like benzodiazepines.

Question 3

What is the clinical application of ethanol?

Answer 3

Can treat ethylene glycol and methanol poisoning by competitively binding alcohol dehydrogenase thus preventing metabolism of the other alcohols into toxic metabolites.

Question 4

Describe the two processes for ethanol metabolism.

Answer 4

Alcohol dehydrogenase (ADH) metabolizes alcohol in the liver and gut for blood ethanol 0.1% uses microsomal ethanol-oxidizing system (P450 enzymes)

Question 5

What toxic metabolite is formed from methanol?

Answer 5

Formaldehyde

Question 6

What toxic metabolite is formed from ethylene glycol?

Answer 6

Oxalic acid (causes severe acidosis and renal damage; oxylate crystals in urine)

Question 7

Describe the mechanism of action of ethanol.

Answer 7

It enhances GABA actions at GABA-A receptors and inhibits NMDA receptors (glutamate receptors). Also increases synaptic concentrations of DA, 5HT, and endogenous opioids in the nucleus accumbens and ventral tegmental area.

Question 8

Describe the mechanism of action and clinical use of acamprosate.

Answer 8

An anti-craving med for recovering alcoholics (also tx epilepsy) that increases GABA-A receptor activity and inhibits glutamatergic receptor activity

*I camp crave alcohol anymore.

Question 9

Describe the mechanism of action and clinical use of clonidine and propanolol.

Answer 9

They activate a2 adrenergic receptors to decrease sympathetic outflow (remember a2 does feedback inhibition of NE). Used for mild ETOH withdrawal sx (anxiety, insomnia, tremors, etc)

Question 10

Describe the mechanism of action of diazepam and its clinical use.

Answer 10

A long-acting benzodiazepine that activates GABA-A receptors in the CNS, increasing affinity for GABA. Treats severe ETOH withdrawal w/ convulsions.

Question 11

Describe the mechanism of action of disulfiram.

Answer 11

It inhibits acetaldehyde dehydrogenase, causing acetaldehyde to persist (results in n/v, headache, and hypotension).

*If I drink I will sulfir (suffer haha)

Question 12

Describe the mechanism and clinical use of fomepizole.

Answer 12

Same as ethanol.

Question 13

Describe the mechanism of action of naloxone and its clinical use.

Answer 13

Short-acting opioid antagonist used for opioid abuse/overdose

Question 14

Describe the mechanism of action of naltrexone.

Answer 14

Suppresses the rewarding effects of ETOH.

*You shalt nalt be rewarded.

Question 15

What side effects are associated with naltrexone?

Answer 15

Hepatotoxicity in high doses, severe opioid withdrawal in dependent individuals (don’t give to liver pts)

Question 16

Describe the mechanism of action and clinical use of n-acetylcysteine.

Answer 16

Neutralizes acetaminophen metabolites by P450 enzymes. Treats chronic alcoholics suspected of acetaminophen poisoning

*N(eutralizes)-acet(aminophen) metabolites

Question 17

Describe the mechanism of action and clinical use of topiramate.

Answer 17

Enhances GABA-A receptor activity and inhibits AMPA/kainate receptors (glutamate receptors). Used to treat epilepsy, migraines, reduces relapse by anti-craving mechanism (mech. for that is unknown). Does NOT tx withdrawal.