EtOH Use and Abuse

Question 1

Pt is experiencing symptoms of EtOH withdrawal. What do you give them, from a pharm standpoint? How will they help?

Answer 1

Benzos
- relax the agitated pt

Thiamine
- bc chronic alcoholics are generally malnourished and need thiamine to metabolize glucose.

Question 2

Pt is experiencing acute methanol or ethylene glycol intoxication. What two drugs can you give them to treat this? How do they work?

Answer 2

EtOH for methanol
Fomepizole for ethylene glycol

both - inhibit alcohol dehydrogenase –> can’t convert methanol/ethylene glycol to their toxic metabolites.

Question 3

Disulfram prevents the action of this enzyme, resulting in an accumulation of this metabolite of EtOH that causes flushing and nausea.

What population’s enzyme deficiency mimics this?

Answer 3

–I Aldehyde dehydrogenase —> accu. of acetaldehyde –> nausea/flushing

Asian flush due to deficiency of aldehyde dehydrogenase

Question 4

In what population is CYP metabolism of EtOH important?

Answer 4

Alcoholics.

In mild-moderate drinkers, CYPs do NOT metabolize EtOH

Question 5

Some alcoholics find accumulation of acetaldehyde pleasurable. How is this possible?

Answer 5

Acetaldehyde accumulation in the periphery is unpleasant but pleasurable in the ventral tegmental area (VTA) where it reinforces alcohol seeking behavior. A polymorphism of aldehyde dehydrogenase causes this.

Question 6

How does EtOH lead to toxic effects of acetaminophen?

How do you treat this toxicity?

Answer 6

EtOH induces CYP2E1
—> more production of NAPQI (toxic!)

N-acetylcysteine–> produces fresh substrate Glutathione to accelerate metabolism of NAPQI
—> cysteine and mercaptopuric acid conjugates (non-toxic)

Question 7

What are the non-toxic metabolites of Tylenol?

Answer 7

Sulfate conjugate

Glucuronide conjugate

Question 8

Who is more at risk for Tylenol toxicity, acute drinkers or chronic alcoholics?

Answer 8

Chronic alcoholics, bc they have baseline elevations of CYP2E1 that quickly converts acetaminophen—> NAPQI

Question 9

Describe the physiological effects on a pt w/ a BAL (mg/dL) of:

Answer 9

limited muscular incoordination

Question 10

Describe the physiological effects on a pt w/ a BAL (mg/dL) of:
50-100

Answer 10

Pronounced incoordination

Question 11

Describe the physiological effects on a pt w/ a BAL (mg/dL) of:
100-150

Answer 11

Mood and personality changes; intoxication over the legal limit in most states.

Question 12

Describe the physiological effects on a pt w/ a BAL (mg/dL) of:
150-400

Answer 12

Nausea, vomiting, marked ataxia, amnesia, disarthria

Question 13

Describe the physiological effects on a pt w/ a BAL (mg/dL) of:
>400

Answer 13

Coma, respiratory insufficiency, death

Question 14

What impact does EtOH have on:

GABAa?

Answer 14

GABA release, ^ receptor density

- hence sedation/depression!

Question 15

What impact does EtOH have on:

NMDA?

Answer 15

Inhibition of postsynaptic NMDA receptors
Chronic use leads to upregulation —> seizures, CNS overstimulation during withdrawal

Initial inhibition leads to BLACKOUTS

Question 16

What impact does EtOH have on:

Dopamine?

Answer 16

^ synaptic DA, ^ effects on VTA/nucleus accumbens reward

Question 17

What impact does EtOH have on:

ACTH?

Answer 17

^ CNS and BV levels of ACTH

Question 18

What impact does EtOH have on:

Opioid receptors?

Answer 18

Release of B endorphins. Activation of mu receptors.

Question 19

What impact does EtOH have on:

5-HT?

Answer 19

^ in 50HT synaptic space

Question 20

What impact does EtOH have on:

Cannabinoids?

Answer 20

^ CB1 activity

–> changes in DA, GABA, Glutamate activity

Question 21

EtOH leads to CV depression or elevation in function?

How does this happen?

Answer 21

Depression

• relaxes vascular SM
• incr. gastric BF
• possible hypothermia

Question 22

More weight = incr/decr in BAL?

Answer 22

lower BAL

Question 23

Higher BMI = incr/decr in BAL?

Answer 23

Higher, bc EtOH will not distribute into adipose tissue

Question 24

Female gender = incr/decr in BAL?

Why?

Answer 24

Incr
Females absorb more EtOH from gut.
Generally they have lower weights.
Higher % body fat in women.

Question 25

Chronic EtOH consumption leads to liver dysfunction that results in hypoglycemia. What is going on here?

Answer 25

Inhibits gluconeogenesis (done by liver!)

Question 26

How does chronic EtOH consumption lead to endocrine dysfunction?

Answer 26

Decr. corticosteroid synthesis--> endocrine dysfunction

Question 27

What cardiac effects can very high BALs resulting from acute binge drinking cause?

Answer 27

Arrythmias

Question 28

Chronic alcoholics are more susceptible to this type of infection:

Answer 28

Pneumonia

Question 29

Fetal alcohol syndrome is characterized by:

Answer 29

``` intrauterine growth retardation microcephaly poor coordination midfacial underdevelopment minor joint abnormalities -congenital heart defects/subtle neurologic deficits also reported ```

Question 30

Pt comes into your ED obviously EtOH intoxicated. What is your course of action?

Answer 30

ABCs Thiamine THEN Dextrose Correct electrolyte issues

Question 31

Describe the pharmacokinetic issues that alcohol presents, as they pertain to interactions with other drugs in general.

Answer 31

EtOH increases teratogenicity of concurrent drugs with such effects through changes in metabolism. EtOH increases absorption of both itself and concurrent drugs.

Question 32

Describe the effect EtOH has on bleeding risks involved with NSAIDs and anticoags.

Answer 32

Increases bleeding risk associated w/ NSAIDs and anticoagulants

Question 33

What influence does EtOH have on diabetics on medications for diabetes?

Answer 33

Incr. risk of hypoglycemia

Question 34

What drugs are known to have disulfram-like effects?

Answer 34

Sulfonylureas, Cefotetan, ketoconazole, procarbazine

Question 35

How does Naltrexone work?

Answer 35

It is a u opioid antagonist. Decr. desire for EtOH by decr. reward felt. Good for addicts!

Question 36

How does acamprosate work?

Answer 36

Weak NMDA antagonist, and GABAa activator. Decr. "need" for alcohol in people withdrawing.

Question 37

The reward centers targeted by EtOH are found where in the brain? Does EtOH directly stimulate these areas?

Answer 37

The corticomesolimbic dopaminergic pathway- extends from VTA to nucleus accumbens EtOH INDIRECTLY stimulates the VTA-NA through the release of other NTs: opioids, 5-HT, glutamate, GABA, and ACh.

Question 38

Both ethylene glycol and methanol are known to have this toxic effect:

Answer 38

acidosis | SEVERE in methanol

Question 39

In addition to acidosis, ethylene glycol also causes:

Answer 39

nephrotoxicity

Question 40

In addition to acidosis, methanol also causes:

Answer 40

retinal damage. And is metabolized to formaldehyde which will be smelled on the pt's breath when they present.