Alcohol Use and Abuse

Question 1

Question 2

What are some alternatives to ethanol (i.e. for alcoholics who cant find beer)?

Answer 2

metahnol or ethylene glycol (but remember these produce toxic metabolites and preventation of their metabolism is accomplished by giving ethanol or fomepizole)

Question 3

How migh alcohol withdrawal present?

Answer 3

vitamin deficiency (need to thiamine usually)

agitation (need for benzos)

Question 4

Again, acute methanol or ethylene glycol intoxication is best tx with what?

Answer 4

ethanol or fomepizole

Question 5

What are some options for tx alcohol dependency?

Answer 5

Disulfram

Naltrexone

Acamprosate

Question 6

How is ethanol metabolized?

Answer 6

Occurs primarily in the liver where it is first emtabolized to acetaldehyde and subsequently to acetate via alcohol dehydrogenase and aldehyde dehydrogenase, respectively.

Question 7

T or F. The metabolism of alcohol is a zero order kinetic phenomenon

Answer 7

T. Like phenyotin and aspirin

Question 8

Normally, there is very little CYP involvement in ethanol metabolism, except:

Answer 8

In the case of ethanol overdose in which it may become neccessitated

Question 9

How does disulfram work?

Answer 9

It encourages abstinence by preventing the metabolism of acetaldehyde, thus leading to accumulation of this normally transient intermediate, which causes a feeling nausea and flushing

Question 10

Question 11

Usually accumulation of acetaldehyde causes a sickening feeling. When is this effect different?

Answer 11

Some alcoholics find the effects of acetaldehyde pleasurable (especially Asians with a ALDH2*1/2*2 heterozygosity; may explain alcoholism prevalance among Native Americans) in which its effects are still unpleasant in the periphery but pleasurable in the VTA where it promotes dopamine release

Question 12

Although CYP450 is not a major player in the metabolism of ethanol, ethanol is an important inducer of _____

Answer 12

CYP2E1 (so alcohol can affect the metabolism of concurrent drugs)

Question 13

What is a major DDI with ethanol due to its inducing of CYP2E1?

Answer 13

Tylenol (acetaminophen) b/c Tylenol is normally conjugated with either a sulfate or to a glucuronide, but is more commonly metabolized to NAPQI in the presence of alcohol which depletes glutathionine

Question 14

What is the antidote to acetaminophen OD?

Answer 14

N-acetylcysteine

Question 15

Question 16

Unlike most drugs, ethanol does not act upon one specific receptor, but many. Describe some of the NTM effects

Answer 16

1) Increases GABA release and receptor density
2) Inhibits postsynaptic NMDA receptors (upregulation with chronic use)
3) Increases synaptic DA and its effects on the ventral tegmentum/nucleus accumbens
4) Increases CNS ACTH and opiods
5) Release of serotonin
6) Inhibition of glutamate release

Question 17

Answer 17

Question 18

How does chronic alcohol consumption affect the body?

Answer 18

Dont know what causes the peripheral neuropathy

Question 19

Thiamine deficiency in alcoholics can lead to what?

Answer 19

Wernicke Encephalopathy with its classic triad of ocular motor abnormalities, cerebellar dysfunction, and an altered mental state (confabulations)

Question 20

Question 21

Question 22

How does fetl alcohol syndrome arise?

Answer 22

Ethanol can easily pass through the placenta and fetal levels closely reflect that of the maternal circulation. Fetuses have a general inability to metabolize ethanol and the earlier the exposure occurs, the more severe the outcome. (I.e. if exposure occurs in the 3rd trimester, might only see subtle neurologic deficits, but organogenesis has already largely completed)

Question 23

How does FAS present?

Answer 23

Question 24

Answer 24

Question 25

What drugs produce disulfram-like effects?

Answer 25

Sulfonylureas, cefotetan, ketoconazole, and procarbazine

Question 26

Question 27

Answer 27

Question 28

Answer 28

Question 29