Sunday 23 February 2014

Drug Induced Liver Disease (Hepatotoxicity)-Chapter 13-IMPORTANT EXAMPLES OF DRUG-INDUCED LIVER DISEASES DRUGS Part-3



Amoxicillin and clavulanic acid:-
          Amoxicillin is an antibiotic that is related to penicillin and ampicillin. It is effective against many bacteria such as H. influenzae, N. gonorrhea, E. coli, Pneumococci, Streptococci, and certain strains of Staphylococci . Addition of clavulanic acid to amoxicillin amoxicillin and clavulanic acid enhances the effectiveness of amoxicillin against many other bacteria that are ordinarily resistant to amoxicillin.
Amoxicillin and clavulanic acid has been reported to cause cholestasis with or without hepatitis. Amoxicillin and clavulanic acid-induced cholestasis is rare; approximately 150 cases of liver disease associated with Amoxicillin and clavulanic acid have been reported. Symptoms of cholestasis (jaundice, nausea, itching) usually occur 1-6 weeks after starting Amoxicillin and clavulanic acid, but the onset of liver disease can occur weeks after stopping the Amoxicillin and clavulanic acid. Most patients recover fully in weeks to months after stopping the medication, but rare cases of liver failure, cirrhosis, and liver transplantation have been reported.
        Other antibiotics have been reported to cause liver disease. Some examples include minocycline (an antibiotic related to tetracycline), and Cotrimoxazole (a combination ofsulfamethoxazole and trimethoprim).
Amoxicillin:
        Amoxicillin causes a moderate rise in SGOT levels, SGPT levels, or both, but the significance of this finding is unknown. Hepatic dysfunction, including jaundice, hepatic cholestasis, and acute cytolytic hepatitis, have been reported.
Nonsteroidal antiinflammatory drugs (NSAIDs):
               Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly prescribed for the bone and joint-related inflammation such as arthritis, tendinitis and bursitis. Examples of NSAIDs include aspirin, indomethacin, ibuprofen, naproxen, piroxicam, and nabumetone.
              NSAIDs are safe when used properly and as prescribed by doctors; however, patients with cirrhosis and advanced liver disease should avoid NSAIDs since they can worsen liver function (and cause kidney failure as well).
            Serious liver disease (such as hepatitis) from NSAIDs, occur rarely (in approximately 1-10 patients per 100,000 who use the drugs). Diclofenac  is an example of an NSAID that has been reported to cause hepatitis slightly more frequently, in approximately 1-5 per 100,000 users of the drug. Hepatitis usually resolves completely after stopping the drug. Acute liver failure and chronic liver disease, such as cirrhosis, have been reported rarely.
Tacrine:
            Tacrine (Cognex) is an oral medication used for treating Alzheimer's disease. (The FDA approved tacrine in 1993.) Tacrine has been reported to cause abnormal elevations in blood liver enzymes commonly. Patients may report nausea, but hepatitis and serious liver disease are rare. Abnormal tests usually become normal after tacrine is stopped.
Disulfiram:
         Disulfiram is a medication occasionally prescribed to treat alcoholism. It discourages drinking by causing nausea, vomiting, and other unpleasant physical reactions when alcohol is ingested. Disulfiram has been reported to cause acute hepatitis. In rare cases, disulfiram-induced hepatitis can lead to acute liver failure and liver transplantation.
Rifampin:
        Rifampin is usually administered with INH. On its own, rifampin may cause mild hepatitis, but this is usually in the context of a general hypersensitivity reaction. Fatalities associated with jaundice have occurred in patients with liver disease and in patients taking rifampin with other hepatotoxic agents. Careful monitoring of liver function (especially SGPT/SGOT) should be performed prior to therapy and then every 2-4 weeks during therapy. In some cases, hyperbilirubinemia resulting from competition between rifampin and bilirubin for excretory pathways of the liver can occur in the early days of treatment. Isolated cholestasis also may occur. An isolated report showing a moderate rise in bilirubin and/or transaminase levels is not in itself an indication for interrupting treatment. Rather, the decision should be based on repeated test results and trends in conjunction with the patient's clinical condition.

 Valproic acid and divalproex sodium: 
    • Microvesicular steatosis is observed with alcohol, aspirin, valproic acid, amiodarone, piroxicam, stavudine, didanosine, nevirapine, and high doses of tetracycline. Prolonged therapy with methotrexate, INH, ticrynafen, perhexiline, enalapril, and valproic acid may lead to cirrhosis. Valproic acid typically causes microsteatosis. This drug should not be administered to patients with hepatic disease; exercise caution in patients with a prior history of hepatic disease. Those at particular risk include children younger than 2 years, those with congenital metabolic disorders or organic brain disease, and those with seizure disorders treated with multiple anticonvulsants.
    • Hepatic failures resulting in fatalities have occurred in patients receiving valproic acid. These incidents usually occur during the first 6 months of treatment and are preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, vomiting, and even loss of seizure control. Liver function tests should be performed prior to therapy and at frequent intervals, especially in the first 6 months. Physicians should not rely totally on laboratory results; they should also consider findings from the medical history and physical examination.

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