Page 2479 - Cote clinical veterinary advisor dogs and cats 4th

1231.e2 Hepatotoxic Drugs

Hepatotoxic Drugs
VetBooks.ir Drug Species Toxicity Latency Clinical Scenario Hepatic Biopsy Risk Factors

Acetaminophen Dog D: Cytotoxic, Within hours ALI to ALF Acute centrolobular to Dose dependent
mitochondrial toxin panlobular necrosis Glutathione depletion
Amiodarone Dog I: Mitochondrial toxin 6 d to 8 mo ALI Lipidosis/degeneration Dose dependent
Dobermans?
Azathioprine Dog D?: Cytotoxic ? Asymptomatic ↑LE, ALI ? Dose dependent?
Carprofen Dog I: Cytotoxic, 5-30 d ALI to ALF Cytotoxic Labradors?
immunoallergenic Necroinflammatory
Corticosteroids Dog D: Vacuolar Days to weeks Asymptomatic (for liver signs), Vacuolar change Dose and duration of
↑LE Ballooning degeneration therapy
Often associated with other Single cell necrosis Individual susceptibility
signs, e.g., PU/PD, panting,
polyphagia, muscle
wasting/weakness
Diazepam Cat I: Cytotoxic 5-10 d ALI to ALF Necrosis Oral form
Doxycycline Dog/Cat I? ? Soon after Asymptomatic ↑LE in up to ? Dose and age dependent
starting 40%
ALI
Glipizide Cat I: Cholestatic ? ALI ? ?
Griseofulvin Cat I 6-13 wk ALI; ↑LE and bilirubin ? ?
Halothane/ Dog I: Immunoallergenic 1-7 d ALI to ALF Acute necrosis Previous exposure
methoxyflurane necessary
Ketoconazole/other Dog/Cat D? Within days Asymptomatic ↑LE ? May develop hepatic
azoles ALI tolerance
Lomustine (CCNU) Dog I: Cytotoxic 2-49 wk Asymptomatic ↑LE (60%- Chronic inflammation/ Boxers and dogs <5 yr
1-3 doses 80%) but vacuolar degeneration/ Cumulative dose
CLI/CLF in 1%-6% fibrosis SAMe/silymarin may
retard damage
Methimazole Cat I: Cytotoxic or Within 3 mo ALI Acute necrosis or ?
immunoallergenic acute cholestasis
Methotrexate Dog I? 13 wk Acute to chronic Hepatocellular necrosis/ ?
vacuolar change
Methyltestosterone Dog Cholestatic ? ALI Acute cholestasis ?
Mitotane (Lysodren) Dog I? 2 wk ALI Vacuolar degeneration/ ?
centrilobular collapse
Nitrofurantoin Dog I? ≈5 d ALI ? ?
Phenazopyridine Dog/Cat D?: Cytotoxic Within hours ALI Acute centrolobular Metabolized to
Along with myopathy, necrosis, degeneration acetaminophen
KCS, hemolytic anemia,
methemoglobinemia
Phenobarbital Dog I and D: Cytotoxic Weeks to years ALF (rare) Acute necrosis (rare) Dose dependent in some
CLI, CLF Chronic patients; idiosyncratic
May be associated with SND necroinflammatory in others
Stanozolol Cat D?: Cholestatic 7-10 d ALI Diffuse lipidosis and ?
ALF cholestasis
Sulfonamides Dog I: Cytotoxic, cholestatic 5-36 d ALI to ALF Acute necrosis or Dose dependent
Concurrent skin eruption, destructive cholangitis Dobermans, Samoyeds,
IMHA, ITP, GN, KCS, and schnauzers
polyarthropathy possible
Tetracycline Dog/Cat I? 3 d ALI Lipidosis ?
Zonisamide Dog I? 10-21 d ALI to ALF Acute necrosis ?
ALF, Acute liver failure with coagulopathy and encephalopathy with high mortality; ALI, acute liver injury; CLF, chronic liver failure with cirrhosis/portal hypertension; CLI, chronic liver injury; D, direct, dose
dependent, or intrinsic toxic; GN, glomerulonephritis; I, idiosyncratic toxin; IMHA, immune-mediated hemolytic anemia; ITP, idiopathic thrombocytopenia purpura; KCS, keratoconjunctivitis sicca; ↑LE, increased
serum liver enzyme activity; PU/PD, polyuria/polydipsia; SAMe, S-adenosylmethionine; SND, superficial necrolytic dermatitis; ?, phenomena not well studied in veterinary patients.
Reproduced from the third edition in unabridged form.

THIRD EDITION AUTHOR: Cynthia R. L. Webster, DVM, DACVIM

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