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Clinical Pharmacology > Hepatobiliary Therapeutics > Flashcards

Hepatobiliary Therapeutics Flashcards

1
Q

what is cholestasis?

A

slowing of bile flow

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2
Q

what small molecules are antioxidants?

A

glutathione
vitamin E

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3
Q

what is the rate-limiting step of glutathione biosynthesis?

A

cysteine

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4
Q

what does vitamin E inhibit?

A

lipid peroxidation

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5
Q

what is vitamin K deficiency with cholestasis due to?

A

decreased absorption from fat malabsorption due to lack of micellar concentration of bile acids in the duodenum
anorexia: decreased intake of vitamin K
antibiotic modulation bacterial flora: decreased production of vitamin K

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6
Q

does reduced excretion of copper due to cholestatic liver disease happen in dogs?

A

no

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7
Q

what can secondary accumulation of copper be due to?

A

reduced excretion
increased intake: copper in diet

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8
Q

what does hepatic copper accumulation create?

A

a pro-oxidant state in the liver

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9
Q

why does hepatic encephalopathy occur?

A

absorption of GI toxins that escape hepatic metabolism: ammonia

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10
Q

how does ursodeoxycholate work?

A

replaces the more hydrophobic, hepatotoxic bile acids
cholerectic: increases bile flow by stimulating secreetion of bicarbonate rich fluid from the bile ducts

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11
Q

how does ursodeoxycholate maintain mitochondrial and endoplasmic reticulum integrity?

A

prevents endoplasmic reticulum stress: chaperone function
replenishes mitochondrial glutathione levels
inhibits reactive oxygen species

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12
Q

what are the major side effects of ursodeoxycholate?

A

diarrhea
vomiting
both rare

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13
Q

how does S-adenosylmethionine help with methylation of membrane phospholipids?

A

stabilizes membranes
promotes maintenance of mitochondrial glutathione stores

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14
Q

why is it good that S-adenosylmethionine increases intracellular glutathione?

A

glutathione depletion accompanies hepatic disease
major anti-oxidant in the liver

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15
Q

how is the bioavailability of S-adenosylmethionine?

A

very unstable: recommend use of Nutramax products

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16
Q

what are the major indications for S-adenosylmethionine?

A

chronic inflammatory hepatobiliary disease: chronic hepatitis in dogs
healing phase of hepatic toxicity
prevent hepatic drug toxicity

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17
Q

what does N-acetylcysteine do?

A

delivers cysteine to the liver
anti-oxidant: increases glutathione

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18
Q

what are the indications for N-acetylcysteine?

A

acute liver disease
antidote for acetaminophen toxicity

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19
Q

how is N-acetylcysteine given?

A

IV, not oral

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20
Q

what have recent NIH clinical trials shown with silymarin?

A

failed to show efficacy with standard doses and preparation

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21
Q

how is the bioavailability of silymarin?

A

poor

22
Q

what is the treatment of copper associated hepatopathy?

A

decrease copper intake
decrease absorption of copper from the gastrointestinal tract
enhance copper excretion with copper chelation therapy
anti-oxidants

23
Q

what does D-penicillamine do?

A

binds copper and promotes urinary copper excretion

24
Q

what is the most common adverse effects of penicillamine?

A

gastrointestinal upset

25
Q

what does zinc do?

A

blocks copper intestinal copper absorption

26
Q

what are the side effects of zinc?

A

vomiting
iron deficiency
hemolytic anemia

27
Q

how can you treat vitamin K deficiency?

A

parenteral vitamin K1 (phytonadione)

28
Q

does liver failure coagulopathy due to synthetic failure respond to vitamin K?

A

no: need plasma

29
Q

what does lactulose do?

A

osmotic cathartic
acidifies colon trapping NH3 as NH4+

30
Q

what are the side effects of lactulose?

A

diarrhea
hypercalcemia in cats

31
Q

which anitbiotics can be used for hepatic encephalopathy?

A

metronidazole
amoxicillin

32
Q

how can you treat hepatic encephalopathy in the diet?

A

moderate protein restriction
soy, diary, and vegetable sources

33
Q

what are some clinical syndromes accompanying hepatobiliary disorders?

A

cholestasis
depletion of anti-oxidant defenses
vitamin K deficiency
excess copper accumulation
hepatic encephalopathy

34
Q

which dog breeds are predisposed to copper storage disorders?

A

bedlington terriers
dalmations
some labradors and dobermans

35
Q

what does a pro-oxidant state in the liver cause?

A

hepatocellular degeneration/necrosis/apoptosis
chronic inflammation/fibrosis

36
Q

what is hepatic encephalopathy?

A

neuroinhibitory state

37
Q

what is the general mechanism of action of URSO?

A

cytoprotection and choleresis
anti-apoptotic

38
Q

what is absorption like of urso?

A

enhanced in presence of food
decreased by aluminum containing antacids
decreased in advanced cholestasis

39
Q

what does methylation of DNA by SAMe do?

A

controls transcription of inflammatory/pro-apoptotic cytokines

40
Q

how must SAMe be formulated?

A

as stable salt

41
Q

has SAMe been shown to increase hepatic glutathione levels in dogs and cats?

A

yes

42
Q

what does N-acetylcysteine do in acute liver failure?

A

reverses microcirculatory disturbance

43
Q

what are the side effects of N-acetylcysteine?

A

rare anaphylactic reaction
vomiting
bronchoconstriction with nebulized as mucolytic

44
Q

what does silymarin do?

A

inhibits drug metabolizing enzymes
may undergo some extrahepatic circulation

45
Q

how can vitamin E be administered?

A

better absorption with food
oral administration only

46
Q

what are the actions of vitamin E?

A

decreases lipid peroxidation
decreases lipoxygenase activity, collagen expression and inhibits monocyte/neutrophil adhesion

47
Q

what can you not give D-penicillamine with?

A

zinc

48
Q

what are the rare side effects of penicillamine?

A

fever
cytopenias
lymphadenopathy
skin hypersensitivity reactions
immune-complex glomerulonephropathy

49
Q

what is the liver disease dose of metronidazole?

A

7mg/kg q12h

50
Q

what is lactulose used to treat?

A

hepatic encephalopathy

51
Q

what is used to treat hepatic encephalopathy?

A

lactulose
antibiotics
protein-restricted diet

Clinical Pharmacology (19 decks)

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