Alcohol Misuse

Question 1

Comparison of drug harm

Answer 1

-Alcohol by far worst
-then heroin and crack

Question 2

Normal metabolic fate of alcohol

Answer 2

-90% metabolized by liver
-ethanol to acetaldehyde by alcohol dehydrogenase (ADH)
-acetaldehyde to acetyl CoA by aldehyde dehydrogenase (ALDH)

Question 3

metabolic fate of alcohol in high consumption

Answer 3

-ethanol to acetaldehyde by Microsomal Ethanol Oxidizing System (MEOS)
-NADPH to NADP instead of NAD to NADH

Question 4

Inhibitors of ethanol metabolism

Answer 4

-Fomepizole: inhibits ethanol to acetaldehyde
-Disulfram: inhibits acetaldehyde to acetate

Question 5

Fomepizole

Answer 5

-inhibits ethanol to acetaldehyde in cytosol
-tx methanol and ethylene glycol (antifreeze suicide attempts) poisoning

Question 6

Disulfram

Answer 6

-inhibit acetaldehyde to acetate in mitochondria
-still alcohol effects
=accumlate acetaldehyde

Question 7

PK of alcohol

Answer 7

-dose-dependent
-small inc cause disproportionate inc in concentration
-0-order to 1st-order

Question 8

What will doubling dose of alcohol due to PK

Answer 8

• > 2x concentration

Question 9

Effect of food on ethanol concentration

Answer 9

-food reduce rate of ethanol absorption and reduce saturation of metabolism by slowing gastric emptying
=drinking on empty stomach = inc effect, concentration

Question 10

Clinical effects of ethanol (not objective)

Answer 10

-mild 0.0-0.05%
-inc: 0.06-0.15%
-severe: 0.16-0.3%
-life threatening: 0.31-0.45%

Question 11

Ethanol MOA

Answer 11

-enhance GABA-A = neuronal inhibition
-binds NMDA, inhbits glutamate = dec excitatory effect
-many components are only altered at concentrations above recreational levels

Question 12

Combo alc and benzos

Answer 12

-enhance CNS depression
-don’t drive

Question 13

Alcohol associated organ damage

Answer 13

-liver, colon, breast, oral, rectum cancer
-cardiac, oral, liver, GI, neurologic, lung, muscle, pancreas, bone
-largest death from digestive disease

Question 14

Alcohol withdrawal syndrome

Answer 14

-anxiety, insomnia, GI, HA, palpitations, anorexia
-visual hallucinosis (usually resolves 48h)
-withdrawal tonic-clonic sz (as early as 2h-2days after cessation)
-delirium tremens: agitation, hallucincations, disorientation, tachycardia, HTN, fever, diaphoresis peak 5 days, lasts 7

Question 15

Alcohol Use Disorder

Answer 15

-more ppl than any other substance or mental health disorder
-few ppl seek tx

Question 16

Patho of AUD

Answer 16

1. binge/intoxication stage: basal ganglia
2. withdrawal/negative effect stage: amygdala
3. Preoccupation/anticipation: prefrontal cortex

-really complex

Question 17

Tx approaches for AUD

Answer 17

-Disulfram
-naltrexone
-Acamprosate: blocks glutamate
-also topiramate, gababentin, baclofen (low evidence)

-looking for new drugs for this

Question 18

Disulfram

Answer 18

-inhibit ALDH
-accumulation of acetaldehyde = aversion to alcohol
-also maybe used for cocaine

Question 19

How would targeting opioid or glutaminergic system treat AUD?

Answer 19

-dec dopaminergic input into nucleus accumbens

Question 20

Alcohol Poisoning

Answer 20

-most common among middle aged adults (mostly men)
-CUSP!
-Cold, clammy, pale skin
-Unconsious
-Slow breathing
-Puking uncontrollably