29. Pharmacology of Alcohol PHARM Flashcards Preview

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Flashcards in 29. Pharmacology of Alcohol PHARM Deck (68)
1

define 'proof'.
alcohol marked as 150 proof is what % alc?

proof = %alc by volume *2
150 proof is 75% alcohol by vol.

2

what three systems does alcohol have effect on?

GABA
Glutamate/NMDA
beta-endorphin

3

what does alcohol do to the GABA system? what is the effect?

binds to GABA-A receptor, increasing GABA effect. effect = relaxation, loss of coordination, motor slowing, sedative, anxiolytic. (enhances inhibition)

4

GABA's major action: inhibitory or excitatory?

inhibitory.

5

what does alcohol do to the glutamate system? what is the effect?

NMDA antagonist: inhibits release of presynaptic glutamate. also reduces actions of glutamate at the post-synaptic neuron receptors so DOUBLE EFFECT.
what is the effect? sedation, impaired memory, impaired cognition, hypnotic.

6

glutamate's major action? inhibitory or excitatory?

excitatory

7

what does alcohol do to the opioid system? what is the effect?

indirect stimulation of beta-endorphins. effect = pleasurable euphoric effects via mu receptors

8

what does alcohol do to the dopamine system? what is the effect?

indirect stimulation of dopamine neurons in the VTA. effect = dopa release, pleasure/reward.

9

at the neuron level, what does alc do to beta-endorphin pathways?

stimulates these pathways from the arcuate nucleus; effect is release of dopamine into the nucleus accumbens -> pleasure/reward
also inhibits GABAergic neurons in the VTA, which allows for release of more dopa.
another DOUBLE EFFECT.

10

chronic exposure to alcohol does what to the GABA system?

decreased density of the GABA receptors leading to tolerance/neuroadaptation

11

chronic exposure to alcohol does what to the glutamate system?

compensatory increase in NMDA activity and receptor density leading to tolerance/neuroadaptation

12

extremely condensed version of alc's effects on GABA, glutamate, endorphin systems?

agonizes GABA (incr inhibition)
antagonizes NMDA/glutamate (decr excitation)
indirect action on opioid, dopamine

13

why do women metabolize alcohol more slowly?

smaller amount of body water, also lower activity of gastric enzyme ADH, which metabolizes alc.

14

where is ethanol primarily metabolized?

small amounts excreted unchanged
90% removed by oxidation which occurs in the LIVER.

15

describe the pharmacokinetics of ethanol metabolism - the biochemical pathway.

Ethanol --> (alcohol dehydrogenase) --> Acetaldehyde --> (aldehyde dehydrogenase) --> Acetate --> (CoA) --> Acetyl-CoA --> Co2, water, calories

16

how is alcohol metabolized in the GI tract?

ADH in stomach and small intestine.
early metabolism translates to lower BAC levels??

17

what order kinetics does alcohol metabolism follow in the liver?

zero order kinetics once enzymes (specifically ADH) are saturated. (ie, a constant amount of ethanol is eliminated per unit of time).

18

what amt of BAC can someone metabolize in an hour? have there been outliers from this average?

plasma clearance: generally 0.015 per hour.
group of swedish people has higher rate (prob genetic)
rate increases with alc dependence: some alcoholics can metabolize 0.02 or 0.025 per hr.

19

how many drinks can someone metabolize in an hour?

slightly less than 1. (1.5 oz of 80 proof, 1 oz of 100 proof)
so if you drink 1 per hour, your BAC will rise somewhat but you won't be over the legal limit for over 7 hours

20

the first step of alcohol metabolism requires what as a cofactor?

NAD molecule. This is the first of 2 rate-limiting steps (ethanol to acetaldehyde using alcohol dehydrogenase as an enzyme).

21

what are 4 changes in chemistries that happens with chronic alcohol use?

1. incr production of lactic acid, can result in hyperuricemia and gout
2. incr production of ketone bodies --> ketonemia
3. incr triglyceride synthesis results in a fatty liver
4. decreased gluconeogenesis and liver glycogen cause hypoglycemia

22

what system allows alcoholics to metabolize alcohol at increased rates from average drinkers?

the Microsomal Ethanol Oxidizing System (MEOS). In liver. With BACs in normal range, this system contributes little to metabolism. With BACs over 0.1, this system kicks in. Uses NADPH as a cofactor rather than NAD

23

acetaldehyde metabolism occurs where?

liver

24

how many NAD molecules required to oxidize 1 ethanol molecule?

2

25

second rate-limiting step in alcohol metabolism?

acetaldehyde --> acetate using NAD and aldehyde dehydrogenase.

26

accumulation of what molecule leads to hangovers?

acetaldehyde. directly between the two rate-limiting steps of metabolism.

27

disulfiram is the generic name for what?

antabuse

28

where does disulfiram work? what does it cause?

blocks aldehyde dehydrogenase, which converts acetaldehyde to acetate. causes backup of acetaldehyde; extreme discomfort in people who drink alcohol.

29

when BAC gets to very high levels (0.3, 0.4) a person will have problems with what?

maintaining homeostasis. Pulse, temp, BP , RR will all DROP to dangerous levels. may be incontinent. could result in death.

30

if you see a patient with symmetric peripheral nerve injury (decr reflexes), what might you think?

think that it could be due to alcohol neurotoxicity: distal paresthesias of the hands and feet.

31

Wernicke-Korsakoff syndrome: due to what?

thiamine deficiency

32

Wernicke's encephalopathy: what are the symptoms?

paralysis of the EOM, nystagmus, ataxia, confusion

33

Korsakoff's psychosis: what are sx?

amnesia, lack of insight, apathy. may be permanent damage.

34

treatment for Wernicke-Korsakoff syndrome?

replace thiamine. all patients who present to the emergency department with altered consciousness, seizures or both should receive thiamine

35

most common complication of chronic alcohol consumption?

liver disease

36

what is the progression of liver disease?

scarring, inflammation, cirrhosis. somewhat progressive.

37

tx for liver disease?

transplant, but we do not do this if the pt is still drinking.

38

other effects of chronic alcohol consumption?

susceptibility to gastritis (GI hemorrhage)
pancreatitis
anemia (due to decr nutrition, blood loss due to gastritis, direct effect of alc on bone marrow)

39

tolerance: what happens to the amounts of neurotransmitters and endorphins?

decrease in amount of GABA
incr amount of glutamate
decr amount of dopa

40

tolerance: what happens to the receptors for neurotransmitters and endorphins?

decr density of GABA-A receptors
incr density of NMDA receptors
decr density of DA receptors

41

what is the main thing that happens with abrupt cessation (withdrawal)?

Glutamate Storm: increased glutaminergic activity. yields neuroexcitation incl seizures, delirium.

42

why does the 'glutamate storm' occur with ETOH withdrawal?

with chronic ETOH consumption, you've been producing huge amounts of glutamate to counter the effects of the alcohol. with withdrawal, the glutamate goes unchecked because you've also been decr your native GABA.

43

with ETOH withdrawal, decr GABA activity yields what symptoms?

neuromuscular excitation, tremor, seizures.

44

with ETOH withdrawal, decr dopamine activity yields what symptoms?

anhedonia, lack of motivation, dysphoria

45

with ETOH withdrawal, why can a pt get incr BP and pulse?

at the locus ceruleus, there will be incr dopa, leading to incr NE, incr BP and pulse

46

with alcohol withdrawal syndrome, what treatment is given?

benzos to reverse the glutamate storm. can restore homeostasis. there is no tx for delirium. be careful of hemodynamics, airway.

47

with alcohol withdrawal syndrome, what are the 3 things we want to prevent?

-seizures
-delirium
-wernicke-korsakoff

48

what is the IV fluid that we'd give to someone in ETOH withdrawal? what does it contain?

banana bag
-glucose
-thiamine
-multivits
-folate

49

which benzodiazepines have a shorter duration of action? longer?

shorter: lorazepam, oxazepam
longer: chlordiazepoxide, diazepam

50

Thiamine: class?

vitamin

51

Thiamine: action?

breaks down sugars in diet. helps correct nerve problems due to lack of thiamine in Wernicke-Korsakoff sx.

52

Thiamine: kinetics?

absorbed from GI tract. metabolized by liver

53

Lorazepam: class?

benzodiazepine, GABA modulator, anti-anxiety

54

Lorazepam: action?

binds to central benzo receptors, which interact with GABA receptors. increases (inhibitory) effect of GABA

55

Lorazepam: kinetics?

absorbed rapidly, short acting. metabolized by liver.

56

Lorazepam: advantages?

short acting, lack of active metabolites makes it good for elderly, those with liver disease.

57

Lorazepam: disadvantages?

short acting means more frequent doses. possibility of BZD withdrawal seizure.

58

chlordiazepoxide: class?

benzo, GABA modulator, anxiolytic

59

chlordiazepoxide: benefits?

high bioavailability, used to treat withdrawal

60

chlordiazepoxide: VA?

default drug at VA

61

acamprozate: class?

GABA analog

62

acamprosate: action?

NMDA antagonist, GABA A activator.

63

acamprosate: advantages?

well tolerated, no sig drug interactions, may be effective with naltrexone or disulfiram

64

disulfiram: what is it?

antabuse

65

45yo malnourished homeless in ED for alcohol detox. no liver disease, seizures. initial treatment and detox?

initial treatment: banana bag
detox: lorazepam, chlordiazepoxide

66

40 yo binge drinks and is destroying his marriage. detox drug, administration?

consider disulfiram (antabuse) given by wife.
consider baseline LFTs

67

55 year old male on his second marriage. He has tried to stop in the past without medications, using AA and counseling, but this time he wants to “pull out the stops” and use everything that might help. LFTs are normal, but he has coronary artery disease.
Meds?

naltrexone IM, topirimate

68

64 year old married female who has been drinking a bottle of wine nightly for several years. Her last drink was 1 week ago, but she is having a lot of craving and anxiety. She has a diagnosis of early biliary cirrhosis and is very cautious about taking medication that might affect her liver or interact with other medications.
med?

acamprosate