prajmaline and Cholestasis

3 patients developed transient cholestatic jaundice after administration of prajmalium bitartrate, a class I antiarrhythmic drug. The leukocyte inhibition tests showed 4%, 12% and 15% inhibition, respectively, while eosinophilia was seen in all 3, supporting the assumption that the transient hepatic damage was due to drug exposure. Discontinuing the drug resulted in improvement in the clinical and biochemical findings.

Topics: Adult; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Humans; Male; Middle Aged; Prajmaline

The calcium-ionophore A23187 causes a reversible increase of the hydrostatic pressure in the portal vein of perfused rat liver. Concomitantly, hepatic functions like the production of bile and the transhepatic movement of the bile acid taurocholate are diminished, mainly due to decreased uptake. These phenomena are partly explained by changes in the microcirculation of the liver, visualized by Trypan blue staining. Both the increase in portal pressure and the major part of the decrease of biliary excretion of taurocholate and bile flow are prevented by the addition of the vasodilator papaverine. The type I antiarrhythmic drugs quinidine and N-propylajmaline bitartrate (NPA), at high concentrations, also induce a rise in portal pressure and act as a cholestatic agent. The rise in portal pressure caused by NPA requires the presence of extracellular calcium and is counteracted by papaverine. In contrast to A23187, the cholestasis caused by NPA is not influenced by papaverine. While NPA decreases the hepatic uptake and biliary excretion of taurocholate, papavarine is able to restore only the uptake and not the excretion. The concentration of taurocholate in the bile is not significantly changed by NPA.

Topics: Animals; Anti-Arrhythmia Agents; Bile; Blood Pressure; Calcimycin; Cholestasis; Liver; Male; Microcirculation; Papaverine; Prajmaline; Quinidine; Rats; Rats, Inbred Strains; Taurocholic Acid

Topics: Ajmaline; Arrhythmias, Cardiac; Chemical and Drug Induced Liver Injury; Cholestasis; Diagnosis, Differential; Humans; Male; Middle Aged; Prajmaline

Cholestatic jaundice developed in four patients after the administration of prajmalium bitartrate. The clinical, histologic, ultrastructural, and immunologic findings were determined. In all patients, the clinical and morphologic features indicated idiosyncrasy. Two antibodies distributed in a granular pattern along the bile canaliculi were detected by immunofluorescence in all patients. In one patient, autoimmune markers were found in the serum, and in two instances, the migration-inhibition factor assay against the offending drug was found to be positive. The data support the concept that immunologic processes may participate in the production of the cholestatic syndrome.

Topics: Aged; Ajmaline; Antibodies; Antigen-Antibody Reactions; Cholestasis; Complement System Proteins; Female; Humans; Immunoglobulins; Liver; Lymphocytes; Male; Middle Aged; Prajmaline

Cholestatic jaundice associated with chills, pruritus and blood eosinophilia developed in a patient who received prajmalium bitartrate therapy for ventricular arrhythmia following acute myocardial infarction. Discontinuation of the drug resulted in a spontaneous improvement in the clinical and biochemical findings. Challenge by prajmalium bitartrate caused rapid reappearance of the clinical and biochemical features. In immunological studies, deposits of IgG and IgA were detected at the bile canaliculi by fluorescent staining, and the patient's lymphocytes produced macrophage migration inhibition after in vitro incubation with prajmalium bitartrate. Thus, laboratory results support the assumption of an allergic mechanism.

Topics: Ajmaline; Bile Canaliculi; Cell Migration Inhibition; Cholestasis; Humans; Immunoglobulins; Macrophages; Male; Middle Aged; Prajmaline