Alcohol use & abuse

Question 1

ethanol metabolism

Same for ethanol & ethylene glycol

Answer 1

via OH-H2ase to acetaldehyde
then via ALDH2ase to acetate

methanol … formaldehyde … formic acid
ethylene glycol … … oxalate

Question 2

disulfram (& 4 things w/similar fx)

Answer 2

inhibits ALDH2ase

sulfa drugs, cefotetan, ketoconazole, procarbazine
“SiCK Pee”

Question 3

formepizole

Answer 3

inhibits alcohol dehydrogenase - used for methanol/ethylene glycol/other alcohol poisoning. Original alcohols slowly filtered by kidneys.

Question 4

chronic alcoholism vitamin deficiency

Answer 4

Thiamine (B1), causes Wernike-Korsikoff syndrome (ataxia, eye movement abnormalities, obdundation - can’t see, walk or think straight)

Question 5

treat DTs

Answer 5

thiamine, (maybe dextrose?), BNZ

Question 6

drinking cessation aids

Answer 6

disulfram (sick when drinking)
naltrexone (mu-opioid ant. take away the fun)
acamprosate (NMDA ant., activate GABAR)

Question 7

naltrexone

Answer 7

(mu-opioid ant. take away the fun for drinkers)

Question 8

acamprosate

Answer 8

(NMDA ant., activate GABAR)

Question 9

ALDH21/22

Answer 9

mutation that gives azn flush, acetaldehyde

Question 10

<50 BAL (mg/dL)

Answer 10

limited incoordination, need iodine swabs to check this low

Question 11

50-100 BAL (mg/dL)

Answer 11

pronounced incoordination

Question 12

100-150 BAL (mg/dL)

Answer 12

mood & personality changes, legal limit

Question 13

150-400 BAL (mg/dL)

Answer 13

N/V, ataxia, amnesia, dysarthria (post-exam state)

Question 14

> 400 BAL (mg/dL)

Answer 14

coma, resp insufficiency, death

Question 15

Wernicke-Korsakoff syndrome

Answer 15

Ocular motor abnormalities, cerebellar dysfunction, altered mental state (give thiamine)

Can’t see, walk, or think straight = a drunk

Question 16

alcoholics with acetaminophen - why a problem?

Answer 16

EtOH induces CYP2E1, which metabolizes acetaminophen to NAPQI (toxic).

Tx N-acetylcysteine (serves as substrate to conjugate NAPQI to nontoxic metabolyte)

Question 17

EtOH elimination
distribution
M vs F

Answer 17

In liver: EtOH –> acetaldehyde –> actate (via alcohol & aldehyde dehydrogenase, respectively) zero-order. Distribution in water only, so high body fat –> lower tolerance relative to weight (F).

Question 18

EtOH actions/rewards

Answer 18

Upregulates: 
GABA (increases release & receptor density)
DA (NA/VTA)
ACTH (CNS & blood levels) 
Opioid (beta endorphins, activates mu receptors)
5-HT
Cannabanoid activity
Postsynaptic NMDA INHIBITION

Smooth muscle relaxation, vasodilation, CV depression.

DA activity in VTA/NA related to rewards