Alcohol Pharmacology

Front 1

What are the three toxicants discussed?

Back 1

Ethanol
Methanol
Ethylene glycol

Front 2

What are the three antidotes discussed?

Back 2

Disulfiram
Fomepizole
Ethanol

Front 3

What are the two drugs for ethanol withdrawal?

Back 3

Diazepam
Thiamin (Vitamin B1)

Front 4

What are the two drugs for chronic alcoholics?

Back 4

Naltrexone
Acamprosate

Front 5

Through what two general areas do drugs treat alcohol dependency?

Back 5

Changes in ethanol metabolism
Changes in the ventral tegmental area (VTA) and nucleus accumbens (NA) =corticomesolimbic dopaminergic pathway

Front 6

What enzyme does disulfram inhibit?

Back 6

Aldehyde dehydrogenase

Front 7

What enzyme does fomepizole inhibit?

Back 7

Alcohol dehydrogenase

Front 8

What is the general pathway of the metabolism of alcohol?

Back 8

Alcohol -->acetaldehyde -->> acetate

Front 9

Which enzyme deficiency is responsible for Asian flush?

Back 9

Aldehyde dehydrogenase (single nucleotide polymorphic changes)

Front 10

True or false, research indicates that acetaldehyde has effects in the central nervous system pleasure center in the VTA

Back 10

TRUE!
Appropriate levels may give rise to a reinforcement of alcohol seeking behavior

Asians experience increased pleasure from aldehyde buildup after alcohol intoxication

Front 11

Ethanol is an important inducer of which CYP?

Back 11

CYP2E1

Front 12

If CYP2E1 is normal (or not induced by alcohol), what is acetaminophen predominantly conjugated to?

Back 12

Sulfate conjugate (non-toxic)
Glucuronide (non-toxic)

Front 13

If CYP2E1 is induced (by ethanol), what does acetaminophen metabolism give rise to?
What is administered as an antidote for toxicity from acetaminophen?

Back 13

NAPQI (highly toxic) which is then converted to cysteine and mercapturic acid conjugated (non-toxic) after administration of glutathionine (N-acetylcysteine)

Front 14

At what BAL would you see PRONOUNCED incoordination?

Back 14

50-100

Front 15

At what BAL would you see COMA, RESPIRATORY INSUFFICIENCY AND DEATH?

Back 15

>400

Front 16

At what BAL would you see mood and personality changes?

Back 16

100-150

Front 17

At what BAL would you see nausea, vomiting, marked ataxia, amnesia, and dysarthria?

Back 17

150-400

Front 18

What are some key pathways in the brain that ethanol modulates?

Back 18

Inhibitory actions of GABA
Inhibition of stimulatory actions of glutamate system (responsible for blackouts)

Increases in synaptic DA, increased effects on ventral tegmentum/nucleus accumbens reward

Front 19

What are some other acute effects of alcohol? Cardiovascular and uterine

Back 19

CV depressant
Relaxes vascular smooth muscle
--vasodilation
--possible hypothermia
--increased gastric flow
Relaxes uterine smooth muscle

Front 20

Who will have a higher BAL? A person with a larger, leaner body mass or a fat person?

Back 20

The fatty.
(Women have higher BAL's)

Alcohol excluded from fat

Front 21

What is the order of alcohol metabolism?

Back 21

ZERO ORDER PROCESS
(same amour per hour = around one drink)

Front 22

What are some of the chronic effects of ethanol in the liver?

Gluconeogenesis

Back 22

--Decreased gluconeogenesis which leads to hypoglycemia.
--Fatty liver = hepatitis, cirrhosis, and failure

Front 23

What are some GI problems from chronic alcoholism?

Back 23

Bleeding, scarring which leads to absorptive and nutritional deficiencies

Front 24

What are some CNS problems that result from chronic alcoholism?

Back 24

Peripheral neuropathy
Wernicke-Korsakoff syndrome = ataxia, confusion, ocular muscle paralysis

Front 25

What do you treat Wernicke-Korsakoff syndrome with?

Back 25

Thiamine

Front 26

What are some endocrine problems that result from chronic alcoholism?

Back 26

Gynecomastia and testicular atrophy (due to steroid insufficiency)

Front 27

What does a thiamine deficiency cause?

Back 27

Inability to synthesize and replenish critical amino acids and proteins (especially in the CNS).

Front 28

What are some CV effects of chronic alcoholism?

Back 28

HTN, anemia, dilated cardiomyopathy, arrhythmias with binges

Front 29

What are the positive effects of moderate alcohol consumption?

Back 29

Increase in HDL which may protect against CHD

Front 30

What major cancer is increased in alcoholics?

Back 30

GI cancer

Front 31

What are the immune system effects of chronic alcoholism?

Back 31

Enhanced inflammation of liver and pancreas, but reduced immune response in other tissues
--Susceptibility to pneumonia

Front 32

What is usually administered in an "intoxicated" patient?

Back 32

Dextrose (for hypoglycemia)
Thiamine (protect against WK syndrome)

Front 33

What is administered in a "withdrawing" patient?

Back 33

BNZ sedative (long acting diazepam or lorazepam if liver function is a concern)
Lorazepam only processed by gluconuridation (phase II), less susceptible to a prolongation in half life.

Use long acting DIAZEPAM unless concern over hepatic function => use LORAZEPAM

Front 34

What drugs give a "disulfiram-like" effect?

Back 34

Sulfonylureas, cefotetan, ketoconazole, procarbazine

Front 35

What is the mechanism of disulfiram?

Back 35

Inhibits ALDH which increases acetaldehyde.
Abstinence reinforced to avoid adverse reaction.

Front 36

What is the mechanism of naltrexone?

Back 36

Opioid antagonist
Decreases drinking through decreased feeling of reward with alcohol and/or craving

Front 37

What is the mechanism of acamprosate?

Back 37

Weak NMDA antagonist, activates GABA receptors (predominantly GABA)
Decreases mild protracted abstinence syndromes with a decreased feeling of "need" for alcohol

Front 38

The corticomesolimbic dopaminergic pathway (goes from ventral tegmental area (VTA) to nucleus accumbens. It is activated by alcohol through the release of what neurotransmitters?

Back 38

Opioids, serotonin, glutamate, GABA, and acetylcholine

Front 39

What is the product of ethylene glycol metabolism?
Negative effects?
What drug acts inhibits the enzyme involved in this reaction?

Back 39

Oxalic acid (nephrotoxicity and acidosis)
Fomepizole (inhibits alcohol dehydrogenase)

Front 40

What is the product of methanol metabolism?
Negative effects?
What is used to inhibit this pathway?

Back 40

Formaldehyde (formic acid), severe acidosis and retinal damage
Ethanol (competitive inhibitor against toxin) = alcohol dehydrogenase enzyme involved.

Front 41

What are the effects of alcohol on each?

Back 41

Front 42

What effect from alcohol?

When does this occur in pregnancy?

Back 42

Front 43

Back 43