Hepatobiliary Therapeutics

Question 1

what is cholestasis?

Answer 1

slowing of bile flow

Question 2

what small molecules are antioxidants?

Answer 2

glutathione
vitamin E

Question 3

what is the rate-limiting step of glutathione biosynthesis?

Answer 3

cysteine

Question 4

what does vitamin E inhibit?

Answer 4

lipid peroxidation

Question 5

what is vitamin K deficiency with cholestasis due to?

Answer 5

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

Question 6

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

Answer 6

no

Question 7

what can secondary accumulation of copper be due to?

Answer 7

reduced excretion
increased intake: copper in diet

Question 8

what does hepatic copper accumulation create?

Answer 8

a pro-oxidant state in the liver

Question 9

why does hepatic encephalopathy occur?

Answer 9

absorption of GI toxins that escape hepatic metabolism: ammonia

Question 10

how does ursodeoxycholate work?

Answer 10

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

Question 11

how does ursodeoxycholate maintain mitochondrial and endoplasmic reticulum integrity?

Answer 11

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

Question 12

what are the major side effects of ursodeoxycholate?

Answer 12

diarrhea
vomiting
both rare

Question 13

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

Answer 13

stabilizes membranes
promotes maintenance of mitochondrial glutathione stores

Question 14

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

Answer 14

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

Question 15

how is the bioavailability of S-adenosylmethionine?

Answer 15

very unstable: recommend use of Nutramax products

Question 16

what are the major indications for S-adenosylmethionine?

Answer 16

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

Question 17

what does N-acetylcysteine do?

Answer 17

delivers cysteine to the liver
anti-oxidant: increases glutathione

Question 18

what are the indications for N-acetylcysteine?

Answer 18

acute liver disease
antidote for acetaminophen toxicity

Question 19

how is N-acetylcysteine given?

Answer 19

IV, not oral

Question 20

what have recent NIH clinical trials shown with silymarin?

Answer 20

failed to show efficacy with standard doses and preparation

Question 21

how is the bioavailability of silymarin?

Answer 21

poor

Question 22

what is the treatment of copper associated hepatopathy?

Answer 22

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

Question 23

what does D-penicillamine do?

Answer 23

binds copper and promotes urinary copper excretion

Question 24

what is the most common adverse effects of penicillamine?

Answer 24

gastrointestinal upset

Question 25

what does zinc do?

Answer 25

blocks copper intestinal copper absorption

Question 26

what are the side effects of zinc?

Answer 26

vomiting iron deficiency hemolytic anemia

Question 27

how can you treat vitamin K deficiency?

Answer 27

parenteral vitamin K1 (phytonadione)

Question 28

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

Answer 28

no: need plasma

Question 29

what does lactulose do?

Answer 29

osmotic cathartic acidifies colon trapping NH3 as NH4+

Question 30

what are the side effects of lactulose?

Answer 30

diarrhea hypercalcemia in cats

Question 31

which anitbiotics can be used for hepatic encephalopathy?

Answer 31

metronidazole amoxicillin

Question 32

how can you treat hepatic encephalopathy in the diet?

Answer 32

moderate protein restriction soy, diary, and vegetable sources

Question 33

what are some clinical syndromes accompanying hepatobiliary disorders?

Answer 33

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

Question 34

which dog breeds are predisposed to copper storage disorders?

Answer 34

bedlington terriers dalmations some labradors and dobermans

Question 35

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

Answer 35

hepatocellular degeneration/necrosis/apoptosis chronic inflammation/fibrosis

Question 36

what is hepatic encephalopathy?

Answer 36

neuroinhibitory state

Question 37

what is the general mechanism of action of URSO?

Answer 37

cytoprotection and choleresis anti-apoptotic

Question 38

what is absorption like of urso?

Answer 38

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

Question 39

what does methylation of DNA by SAMe do?

Answer 39

controls transcription of inflammatory/pro-apoptotic cytokines

Question 40

how must SAMe be formulated?

Answer 40

as stable salt

Question 41

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

Answer 41

yes

Question 42

what does N-acetylcysteine do in acute liver failure?

Answer 42

reverses microcirculatory disturbance

Question 43

what are the side effects of N-acetylcysteine?

Answer 43

rare anaphylactic reaction vomiting bronchoconstriction with nebulized as mucolytic

Question 44

what does silymarin do?

Answer 44

inhibits drug metabolizing enzymes may undergo some extrahepatic circulation

Question 45

how can vitamin E be administered?

Answer 45

better absorption with food oral administration only

Question 46

what are the actions of vitamin E?

Answer 46

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

Question 47

what can you not give D-penicillamine with?

Answer 47

zinc

Question 48

what are the rare side effects of penicillamine?

Answer 48

fever cytopenias lymphadenopathy skin hypersensitivity reactions immune-complex glomerulonephropathy

Question 49

what is the liver disease dose of metronidazole?

Answer 49

7mg/kg q12h

Question 50

what is lactulose used to treat?

Answer 50

hepatic encephalopathy

Question 51

what is used to treat hepatic encephalopathy?

Answer 51

lactulose antibiotics protein-restricted diet