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Flashcards in Alcohol: use and abuse Deck (47):
1

alcohol dehydrogenase is inhibited by which drug?

fomepizole (drug that is used in the treatment of acute ethanol or ethylene glycol intoxication)

2

disulfiram MOA

inhibits aldehyde dehydrogenase leading to the buildup of acetaldehyde which quickly gives rise to a feeling of nausea and vomiting

3

explain how some alcoholics find acetaldehyde pleasurable

appears to provide dual action
-unpleasant in the periphery
-pleasure in the VTA where it promotes DA release
-condenses w/ DA to make salsolinol (strongly reinforcing agent)

4

asians with what heterozygosity experience significantly more positive feelings after alcohol intoxication?

ALDH2*1/2*2
-Allele assoc. w/ lower prev. of abuse & alcoholism
-acetaldehyde may explain alcoholism prevalence among Native americans

5

which CYP enzyme is induced with extensive alcohol abuse?

CYP2E1

6

with alcoholisms CYP2E1 is induced which leads to the accumulation of what highly toxic metabolic intermediate of acetaminophen metabolism?

NAPQI

7

what molecule is needed to converted NAPQI into Cysteine & mercapturic acid conjugates?

GSH

8

what are the physiologic effects of a pt who has a BAL of 15-400 mg/dL?

N/V, ataxia, amnesia, dysarthria

9

what effect does alcohol have on GABA-A?

increased GABA release, increased receptor density

10

what effect does alcohol have on NMDA?

inhibition of postsynaptic NMDA receptors; w/ chronic use, up-regulation

11

what effect does alcohol have on dopamine?

increases synaptic DA, increased effects on ventral tegmentum (VTA) & nucleus accumbens (NA) reward

12

what effects do alchol have on ACTH?

increase CNS & blood levels of ACTH

13

what effects do alcohol have on opioids?

release of beta-endorphins, activation of mu receptors

14

what effect does alcohol have on 5-HT?

increased 5-HT in the synaptic space

15

what effects do alcohol have on cannabinoid?

increased CB1 activity--> changes in DA, GABA, glutamate activity

16

what are the effects of alcohol on CV, smooth muscle and uterine smooth muscle?

CV depressant
Relaxes smooth muscle (vasodilation, increased gastric bloodflow)
Relaxes uterine smooth muscle

17

which gender has a higher BAL typically?

women

18

why do women typically have a higher BAL than men?

increased absorption
lower weight
more body fat

19

what is the relationship b/w BMI and BAL?

higher BMI = more body fat = small Vd = higher BAL

20

what is the most significant component to adaptation with alcohol?

behavioral and neural adaptation

21

what are the chronic effects of ethanol on the liver?

decreases gluconeogenesis (hypoglycemia)
fatty liver-hepatitis, cirrhosis & failure

22

explain how chronic alcohol use can cause hypoglycemia

alcohol increases the NADH/NAD ratio in the liver, which (via normal ethanol metabolism), causing pyruvate --->lactate and OAA-->malate; therefore this inhibits gluconeogensis

23

explain how chronic alcohol use can cause fatty liver?

alcohol use depletes OAA which shuts down the TCA cycle and this causes acetyl-coA to get shunted into ketone production.

Breakdown of excess malate increases NADPH and thus this increases fatty acid synthesis

24

what are the chronic effects of alcohol on the GI system?

bleeding, scarring causing/exacerbating nutritional deficiencies

25

what are the chronic effects of alcohol on the CNS?

peripheral neuropathy (MC)
Wernicke-korsakoff syndrome (ataxia, confusion, ocular muscle paralysis, treat with thiamine)

26

what is the Wernicke-Korsakoff syndrome classic triad?

ataxia
confusion
opthalmoplegia

Treat with thiamine

27

what are the chronic effects of alcohol on the endocrine system?

gynecomastia & testicular atrophy secondary to steroid insufficiency

28

what are some of the reasons why alcoholics have a thiamine deficiency?

decreased thiamine in diet
decreased thiamine absorption in GI tract
decreased thiamine storage in liver
decreased biosynthesis

29

what are the chronic effects of alcohol on the CV system?

HTN, anemia, dilated cardiomyopathy
arrhythmias w/ binge drinking
Modest alcohol intake increases HDL & may protect against CHD

30

what are the chronic effects of alcohol in regards to cancer?

higher incidence of GI cancer (e.g. esophageal squamous cell carcinoma=upper esophagus)

31

what are the effects of chronic alcohol use on the immune system?

extra inflammation in liver & pancreas, but reduced immune response in other tissues
-chronic alcoholics susceptible to infectious pneumonia

32

what are some of the features of fetal alcohol syndrome?

IUGR
microcephaly
poor coordination
flattened face
minor joint anomalies

33

the fetal alcohol levels reflect the ________

maternal alcohol levels

34

how do you treat a pt intoxicated w/ alcohol in the ER ?

ABCs
Thiamine
Dextrose
Correct electrolytes

35

what are the features of alcohol withdrawal?

insomnia, tremor, anxiety
DTs, and rarely seizures

36

how do you treat alcohol withdrawal?

BNZ sedative
thiamine
correct electrolytes

37

if an alcoholic pt who is withdrawing also has hepatic dysfunction, which BNZ can you give him?

lorazepam (b/c it's only processed by glucuronidation-phase II)

38

name all the drugs you can think of that have disulfiram-like effects?

sulfonylureas
cefotetan
ketoconazole
procarbazine

39

how is naltrexone used in alcoholism?

mu (OP-3) Opioid antagonist; decreases the high you get with drinking

40

how is acamprosate used in alcoholism?

weak NMDA antagonist, activates GABA-A receptors; may decreased mild protracted abstinence syndromes with decreased feeling of need for alcohol

41

alcohol indirectly activates which pathway in the brain?

corticomesolimbic dopaminergic pathway, which goes from VTA to the NA (important in the rewarding effects of many drugs)

42

which enzyme metabolize both ethylene glycol and methanol to other toxic metabolites?

alcohol dehyrogenase

43

how do you treat ethylene glycol/methanol intoxication?

1. treat with fomepizole (inhibits Alcohol DH) and allows renal elimination
2. treat with ethanol and keep at 100 mg/dL to ensure enzyme saturation

44

what is the result of ethylene glycol poisoning?

acidosis, nephrotoxicity

45

what is the result of methanol poisoning?

severe acidosis, retinal damage

46

how is fomepizole administered?

IV infusion

47

ethanol is an _______sedative-hypnotic

addictive