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    Hepatotoxic Drugs

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    ani bandaso
    This document discusses hepatotoxicity caused by drugs. It describes direct hepatotoxicity resulting from chemical or drug metabolite injury to liver cells. Indirect hepatotoxicity occurs through altered metabolism or protein synthesis. Immune reactions can also cause hepatotoxic syndromes mimicking viral hepatitis or inflammatory cholestasis. Diagnosis involves drug history and liver testing. Management includes withdrawing the suspected drug, supportive care, and treating complications. The case study describes a patient with drug-induced mixed cholestatic-cytotoxic hepatic injury likely from chlorpropamide.

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    Hepatotoxic Drugs

    Uploaded by

    ani bandaso
    245 views17 pages
    This document discusses hepatotoxicity caused by drugs. It describes direct hepatotoxicity resulting from chemical or drug metabolite injury to liver cells. Indirect hepatotoxicity occurs through altered metabolism or protein synthesis. Immune reactions can also cause hepatotoxic syndromes mimicking viral hepatitis or inflammatory cholestasis. Diagnosis involves drug history and liver testing. Management includes withdrawing the suspected drug, supportive care, and treating complications. The case study describes a patient with drug-induced mixed cholestatic-cytotoxic hepatic injury likely from chlorpropamide.

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    This document discusses hepatotoxicity caused by drugs. It describes direct hepatotoxicity resulting from chemical or drug metabolite injury to liver cells. Indirect hepatotoxicity occurs through altered metabolism or protein synthesis. Immune reactions can also cause hepatotoxic syndromes mimicking viral hepatitis or inflammatory cholestasis. Diagnosis involves drug history and liver testing. Management includes withdrawing the suspected drug, supportive care, and treating complications. The case study describes a patient with drug-induced mixed cholestatic-cytotoxic hepatic injury likely from chlorpropamide.

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    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    245 views17 pages

    Hepatotoxic Drugs

    Uploaded by

    ani bandaso
    This document discusses hepatotoxicity caused by drugs. It describes direct hepatotoxicity resulting from chemical or drug metabolite injury to liver cells. Indirect hepatotoxicity occurs through altered metabolism or protein synthesis. Immune reactions can also cause hepatotoxic syndromes mimicking viral hepatitis or inflammatory cholestasis. Diagnosis involves drug history and liver testing. Management includes withdrawing the suspected drug, supportive care, and treating complications. The case study describes a patient with drug-induced mixed cholestatic-cytotoxic hepatic injury likely from chlorpropamide.

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    Hepatotoxic Drugs

    Direct Hepatotoxicity:
    It is a dose-related liver cell injury by:
    A chemical e.g. carbon tetrachloride.
    A drug metabolite e.g. acetaminophen.
    Direct Hepatotoxic Drugs
    Examples:
    Aspirin.
    Acetaminophen.
    Amiodarone.
    Alcohol.
    Carbon Tetrachloride .
    Methotrexate.
    Indirect Hepatotoxicity

    It is due to Altered Metabolism.


    Interference with the metabolism of
    bilirubin e.g. by estrogen, androgen or
    rifampicin.
    Interference with protein synthesis
    e.g. corticosteroids and i.v tetracycline
    leading to fatty liver.
    Indirect Hepatotoxic Drugs
    Examples:
    Androgen.
    Estrogen.
    Corticosteroids.
    Tetracycline i.v
    Immune Reaction
    A drug or its metabolite binds to liver cell
    membrane and acts as a hapten.
    It induces a variety of syndromes:
    Inflammatory cholestatic jaundice: It
    causes intrahepatic bile ductules
    obstruction e.g. chlorpromazine &
    chlorpropamide.
    Viral hepatitis-like pattern e.g. repeated
    administration of halothane, isoniazid &
    phenytoin.
    Immune Reaction
    Inflammatory Pattern like viral
    cholestasis hepatitis
    Chlorpromazine. Halothane.

    Chlorpropamide. Isoniazid.

    Erythromycin Phenytoin.
    estolate. Valproic acid.
    Propylthiouracil. Methyldopa.
    Thiazide Acetaminophen.

    Aspirin.

    Nitrofurantoin.
    Diagnosis and Management

    Taking a careful drug history.


    Viral hepatitis should be excluded.
    Exclude other causes of extra- and intra-hepatic
    obstructive jaundice.
    Monitoring liver function tests. Elevation of serum
    transferase enzymes greater than three-fold should
    be an indication for drug withdrawal, even if the
    patient is asymptomatic.
    Avoid diagnostic challenge doses of the offending
    drug because it may precipitate fulminant hepatic
    failure.
    Treatment of jaundice is mainly supportive. It
    includes:
    Withdrawal of the presumed offending drug.
    A high carbohydrate diet, moderate in
    protein & adequate in calories.
    If itching is severe, use cholestyramine to
    enhance bile acid excretion and alleviate the
    symptoms.
    Treatment of complications such as ascites,
    esophageal variceal bleeding accordingly.
    Case study

    Nouf is 72 year-old with a 12 year history of


    type II DM admitted in KFMC with:
    Generalized weakness, loss of appetite, rash
    over the chest & thighs and increasing
    itching.
    She also noted dark urine, light-colored
    stool and yellow pigmentation of the skin.
    Past History:
    DM controlled by diet until one month
    ago when she was started on
    chlorpropamide
    HTN treated with hydrochlorothiazide
    (HCTZ) & methyldopa for the past four
    years.
    General Examinations:
    She appears weak, icteric.

    Slightly tender liver.

    Vital signs within normal.


    Lab. Findings:
    AST: 370 U/L (35 U/L).

    ALT: 740 U/L (0-34 U/L).

    Alkaline phosphatase 537 U/L (30-120 U/L).

    Total/direct bilirubin 87/83 umol/L (17-4


    umol/L).
    Albumin 4.1 gm/dl (4-6 gm/dl).

    All other chemistry data are within normal.


    CBC & differential count are normal.
    Antinuclear antibody and HB-Ag are
    both negative.
    U/S: normal biliary tract, no
    obstruction in bile duct, gallbladder, or
    near the head of pancreas.
    Problem Solving

    This is a case of drug-induced mixed


    cholestatic- cytotoxic hepatic injury.
    Possible causes:
    Hydrochlorothiazide (HCTZ):
    It is unlikely because it is rarely
    associated with allergic cholestatic
    jaundice and it was used for 4 years.
    Methyldopa:
    can cause hepatocellular injury (within
    the 1st three months).
    Rarely causes cholestatic jaundice
    (cannot be ruled out without liver
    biopsy)
    Chlorpropamide:
    Has been reported to cause mixed-
    cholestatic-cytotoxic injury within 2-6
    weeks (most probable cause)
    Treatment
    Stop chlorpropamide & methyldopa and
    substituted them by other drugs.
    Nouf was placed on:
    1200 calories/day (2000-3000 cal/day).
    Low salt diet.
    Lente insulin start by 20U/d and increased
    according to plasma glucose levels.
    HCTZ 50mg BID.
    Cholestyramine 4gm/day PO TID for itching

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