Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quinidine, procainamide and disopyramide are antiarrhythmic drugs in the class 1A category. These drugs have a low toxic to therapeutic ratio, and their use is associated with a number of serious adverse effects during long term therapy and life-threatening sequelae following acute overdose. Class 1A agents inhibit the fast inward sodium current and decrease the maximum rate of rise and amplitude of the cardiac action potential. Prolonged Q-T interval and, to a lesser extent, QRS duration may be observed at therapeutic concentrations of quinidine. With increasing plasma concentrations, progressive depression of automaticity and conduction velocity occur. 'Quinidine syncope' (a transient loss of consciousness due to paroxysmal ventricular tachycardia, frequently of the torsade de pointes type) occurs with therapeutic dosing, often in the first few days of therapy. Extracardiac adverse effects of quinidine include potentially intolerable gastrointestinal effects and hypersensitivity reactions such as fever, rash, blood dyscrasias and hepatitis. Procainamide produces electrophysiological changes that are similar to those of quinidine, although Q-T interval prolongation with the former is less pronounced at therapeutic concentrations. Hypersensitivity reactions including fever, rash and (more seriously) agranulocytosis are associated with procainamide, and a frequent adverse effect requiring cessation of therapy is the development of systemic lupus erythematosus. Of the 3 drugs, disopyramide has the most pronounced negative inotropic effects, which are especially significant in patients with pre-existing left ventricular dysfunction. As with quinidine, unexpected 'disopyramide syncope' at therapeutic concentrations has been described. Anticholinergic side effects are common with this drug and may require cessation of therapy. Disopyramide therapy may unpredictably induce severe hypoglycaemia. Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity. Decreased renal function can cause significant accumulation of procainamide and its active metabolite acecainide (N-acetyl-procainamide), resulting in severe intoxication. Mild to moderate renal dysfunction is less likely to lead to quinidine or disopyramide intoxication, unless renal failure is severe or concurrent hepatic dysfunction is present. Management of acute intoxication with class 1A drugs includes gut decontamination with provision of respiratory support and treatment of seizures as needed. Hypertonic sodium bicarbonate, by antagonising the inhibitory effect of quinidine on sodium conductance, may reverse many or all manifestations of cardiovascular toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Poisoning due to class IA antiarrhythmic drugs. Quinidine, procainamide and disopyramide. 228 95

We report the case of a 19-year-old Laotian patient affected by fulminant hepatitis during the third trimester of her pregnancy after a 1-month administration of quinidine phenylethylbarbiturate. After delivery, the patient underwent orthotopic liver transplantation. The patient was in good condition 16 months after liver transplantation. Quinidine itself or phenylethylbarbiturate may be responsible for fulminant hepatitis in this patient.
 ...
PMID:Quinidine phenylethylbarbiturate-induced fulminant hepatitis in a pregnant woman. A case report. 341 Nov 1

The authors report the case of a 63 year-old woman who developed high-grade fever with chills, nausea, diarrhea, severe pain in the right hypochondrium, and jaundice after one month's treatment with 300 mg of hydroquinidine hydrochloride daily. Serum bilirubin and aminotransferases were slightly increased, while alkaline phosphatases and gamma-glutamyl-transpeptidase serum activities were markedly raised. Histological examination of a liver specimen obtained by the transvenous route showed numerous epithelioid granulomas with giant cell formation and eosinophils in hepatic lobules and portal tracts. Symptoms disappeared three days after withdrawal of the drug, but hepatomegaly and a mild increase in serum gamma-glutamyl-transpeptidase persisted more than eighteen months. Quinidine-induced hepatitis is almost always associated with fever, and, in one-third of the cases, with a pseudo-cholangitis picture. Extrahepatic hypersensitivity manifestations are often present. Histological examination of the liver shows granulomatous or cytolytic hepatitis. Withdrawal of the drug is rapidly followed by a favorable outcome; readministration causes immediate relapse; progression to chronic liver disease has never been reported previously.
 ...
PMID:[Hepatitis caused by quinidine. Study of a case and review of the literature]. 373 35