Sunday 23 February 2014

Drug Induced Liver Disease (Hepatotoxicity)-Chapter 13-IMPORTANT EXAMPLES OF DRUG-INDUCED LIVER DISEASES DRUGS Part-2

Chlorpromazine:
       Chlorpromazine liver injury resembles that of infectious hepatitis with laboratory features of obstructive jaundice rather than those of parenchymal damage. The overall incidence of jaundice is low regardless of dose or indication of the drug. Most cases occur 2-4 weeks after therapy. Any surgical intervention should be withheld until extrahepatic obstruction is confirmed. It is usually promptly reversible upon withdrawal of the medication; however chronic jaundice has been reported. Chlorpromazine should be administered with caution to persons with liver disease.
Methotrexate :
           Methotrexate has been used for the long-term treatment of patients with severe psoriasis, rheumatoid arthritis, psoriatic arthritis, and some patients with Crohn's disease. Methotrexate has been found to be a cause of liver cirrhosis in a dose-dependent fashion. Patients with pre-existing liver diseases, obese patients, and those who drink alcohol regularly are particularly at risk of developing methotrexate-induced cirrhosis. In recent years, doctors have substantially decreased methotrexate liver damage by using low doses of methotrexate (5-15 mg) given once a week and by carefully monitoring liver blood tests during therapy. Some doctors also perform liver biopsies on patients without liver symptoms after two years (or after a cumulative dose of 4 grams of methotrexate) to look for early liver cirrhosis.
Methyldopa:
        Methyldopa is an antihypertensive that is contraindicated in patients with active liver disease. Periodic determination of hepatic function should be performed during the first 6-12 weeks of therapy. Occasionally, fever may occur within 3 weeks of methyldopa therapy, which may be associated with abnormalities in liver function test results or eosinophilia, necessitating discontinuation. In some patients, findings are consistent with those of cholestasis and hepatocellular injury. Rarely, fatal hepatic necrosis has been reported after use of methyldopa, which may represent a hypersensitivity reaction.

Oral contraceptives:
Oral contraceptives can lead to intrahepatic cholestasis with pruritus and jaundice in a small number of patients. Patients with recurrent idiopathic jaundice of pregnancy, severe pruritus of pregnancy, or a family history of these disorders are more susceptible to hepatic injury. Oral contraceptives are contraindicated in patients with a history of recurrent jaundice of pregnancy. Benign neoplasm, rarely malignant neoplasm of the liver, and hepatic vein occlusion have also been associated with oral contraceptive therapy.
Antibiotics
Isoniazid :- 
           Isoniazid has been used for decades to treat latent tuberculosis (patients with positive skin tests for tuberculosis, without signs or symptoms of active tuberculosis). Most patients with isoniazid-induced liver disease only develop mild and reversible elevations in blood levels of AST and ALT without symptoms, but approximately 1-2% of the patients develop isoniazid-induced hepatitis. The risk of developing isoniazid hepatitis occurs more commonly in older patients than younger patients. The risk of serious liver disease is 0.3% in healthy young adults, and rises to more than 2% in patients older than 50. An estimated 5-10% of the patients who develop hepatitis go on to develop liver failure and require liver transplantation. The risk of isoniazid liver toxicity is increased with chronic regular alcohol intake, and with concomitant use of other medications such as Tylenol and rifampin.
           Early symptoms of isoniazid hepatitis are fatigue, poor appetite, nausea, and vomiting. Jaundice may then follow. Most patients with isoniazid hepatitis recover fully and promptly after stopping the drug. Severe liver disease and liver failure mostly occur in patients who continue to take isoniazid after the onset of hepatitis. Therefore, the most important treatment for isoniazid liver toxicity is early recognition of hepatitis and discontinuation of the isoniazid before serious liver injury has occurred.
Erythromycin:
            Erythromycin may cause hepatic dysfunction, including increased liver enzyme levels and hepatocellular and/or cholestatic hepatitis with or without jaundice. A cholestatic reaction is the most common adverse effect and usually begins within 2-3 weeks of therapy. The liver principally excretes erythromycin; exercise caution when this drug is administered to patients with impaired liver function. The use of erythromycin in patients concurrently taking drugs metabolized by the P-450 system may be associated with elevations in the serum levels of other drugs.
Ciprofloxacin:
            Cholestatic jaundice has been reported with repeated use of quinolones. Approximately 1.9% of patients taking ciprofloxacin show elevated SGPT levels, 1.7% have elevated SGOT levels, 0.8% have increased alkaline phosphatase levels, and 0.3% have elevated bilirubin levels. Jaundice is transient, and enzyme levels return to the reference range.
Nitrofurantoin. 
            Nitrofurantoin is an anti-bacterial drug that is used to treat urinary tract infections caused by many gram-negative and some gram-positive bacteria.There are three forms of nitrofurantoin available: a microcrystalline form, a macrocrystalline form, and a sustained release, macrocrystalline form used twice daily.
Nitrofurantoin can cause acute and chronic liver disease. Most commonly, nitrofurantoin causes mild and reversible elevations in blood levels of liver enzymes without symptoms. In rare instances, nitrofurantoin can cause hepatitis.
Symptoms of nitrofurantoin hepatitis include:
·         fatigue,
·         fever,
·         muscle and joint aches,
·         poor appetite,
·         nausea,
·         weight loss,
·         vomiting,
·         jaundice, and
·         sometimes itching.
Some patients with hepatitis also have a rash, enlarged lymph glands, and nitrofurantoin-induced pneumonia (with symptoms of cough and shortness of breath).

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