Hepatobiliary Therapeutics Flashcards
what is cholestasis?
slowing of bile flow
what small molecules are antioxidants?
glutathione
vitamin E
what is the rate-limiting step of glutathione biosynthesis?
cysteine
what does vitamin E inhibit?
lipid peroxidation
what is vitamin K deficiency with cholestasis due to?
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
does reduced excretion of copper due to cholestatic liver disease happen in dogs?
no
what can secondary accumulation of copper be due to?
reduced excretion
increased intake: copper in diet
what does hepatic copper accumulation create?
a pro-oxidant state in the liver
why does hepatic encephalopathy occur?
absorption of GI toxins that escape hepatic metabolism: ammonia
how does ursodeoxycholate work?
replaces the more hydrophobic, hepatotoxic bile acids
cholerectic: increases bile flow by stimulating secreetion of bicarbonate rich fluid from the bile ducts
how does ursodeoxycholate maintain mitochondrial and endoplasmic reticulum integrity?
prevents endoplasmic reticulum stress: chaperone function
replenishes mitochondrial glutathione levels
inhibits reactive oxygen species
what are the major side effects of ursodeoxycholate?
diarrhea
vomiting
both rare
how does S-adenosylmethionine help with methylation of membrane phospholipids?
stabilizes membranes
promotes maintenance of mitochondrial glutathione stores
why is it good that S-adenosylmethionine increases intracellular glutathione?
glutathione depletion accompanies hepatic disease
major anti-oxidant in the liver
how is the bioavailability of S-adenosylmethionine?
very unstable: recommend use of Nutramax products
what are the major indications for S-adenosylmethionine?
chronic inflammatory hepatobiliary disease: chronic hepatitis in dogs
healing phase of hepatic toxicity
prevent hepatic drug toxicity
what does N-acetylcysteine do?
delivers cysteine to the liver
anti-oxidant: increases glutathione
what are the indications for N-acetylcysteine?
acute liver disease
antidote for acetaminophen toxicity
how is N-acetylcysteine given?
IV, not oral
what have recent NIH clinical trials shown with silymarin?
failed to show efficacy with standard doses and preparation
how is the bioavailability of silymarin?
poor
what is the treatment of copper associated hepatopathy?
decrease copper intake
decrease absorption of copper from the gastrointestinal tract
enhance copper excretion with copper chelation therapy
anti-oxidants
what does D-penicillamine do?
binds copper and promotes urinary copper excretion
what is the most common adverse effects of penicillamine?
gastrointestinal upset
what does zinc do?
blocks copper intestinal copper absorption
what are the side effects of zinc?
vomiting
iron deficiency
hemolytic anemia
how can you treat vitamin K deficiency?
parenteral vitamin K1 (phytonadione)
does liver failure coagulopathy due to synthetic failure respond to vitamin K?
no: need plasma
what does lactulose do?
osmotic cathartic
acidifies colon trapping NH3 as NH4+
what are the side effects of lactulose?
diarrhea
hypercalcemia in cats
which anitbiotics can be used for hepatic encephalopathy?
metronidazole
amoxicillin
how can you treat hepatic encephalopathy in the diet?
moderate protein restriction
soy, diary, and vegetable sources
what are some clinical syndromes accompanying hepatobiliary disorders?
cholestasis
depletion of anti-oxidant defenses
vitamin K deficiency
excess copper accumulation
hepatic encephalopathy
which dog breeds are predisposed to copper storage disorders?
bedlington terriers
dalmations
some labradors and dobermans
what does a pro-oxidant state in the liver cause?
hepatocellular degeneration/necrosis/apoptosis
chronic inflammation/fibrosis
what is hepatic encephalopathy?
neuroinhibitory state
what is the general mechanism of action of URSO?
cytoprotection and choleresis
anti-apoptotic
what is absorption like of urso?
enhanced in presence of food
decreased by aluminum containing antacids
decreased in advanced cholestasis
what does methylation of DNA by SAMe do?
controls transcription of inflammatory/pro-apoptotic cytokines
how must SAMe be formulated?
as stable salt
has SAMe been shown to increase hepatic glutathione levels in dogs and cats?
yes
what does N-acetylcysteine do in acute liver failure?
reverses microcirculatory disturbance
what are the side effects of N-acetylcysteine?
rare anaphylactic reaction
vomiting
bronchoconstriction with nebulized as mucolytic
what does silymarin do?
inhibits drug metabolizing enzymes
may undergo some extrahepatic circulation
how can vitamin E be administered?
better absorption with food
oral administration only
what are the actions of vitamin E?
decreases lipid peroxidation
decreases lipoxygenase activity, collagen expression and inhibits monocyte/neutrophil adhesion
what can you not give D-penicillamine with?
zinc
what are the rare side effects of penicillamine?
fever
cytopenias
lymphadenopathy
skin hypersensitivity reactions
immune-complex glomerulonephropathy
what is the liver disease dose of metronidazole?
7mg/kg q12h
what is lactulose used to treat?
hepatic encephalopathy
what is used to treat hepatic encephalopathy?
lactulose
antibiotics
protein-restricted diet
