ajmaline and Cholestasis

A 60 years old woman was admitted for jaundice and fever which appeared after a treatment with ajmaline-butabarbital for two-weeks. Abdominal ultrasound examination and endoscopic retrograde cholangiography were normal. Mitochondrial antibodies were absent. Jaundice persisted for three years, associated with diffuse cutaneous xanthomatosis. Five years later, alkaline phosphatases remained elevated. A liver biopsy showed vanishing interlobular bile ducts with centrolobular cholestasis and ductular proliferation. We suggest that ajmaline can induce long lasting cholestasis due to damage to the intrahepatic bile ducts. The responsibility of butabarbital and the relationship with primary biliary cirrhosis are discussed.

Topics: Ajmaline; Barbiturates; Chemical and Drug Induced Liver Injury; Cholestasis; Drug Combinations; Female; Humans; Liver; Middle Aged

2 cases of cholestatic hepatitis due to preajmaline recovered when the drug was stopped. One was a 40-year-old woman, and the other a 74-year-old man whose jaundice lasted for 8 months. Approximately 40 patients with preajmaline-induced hepatitis have been described in the literature. All recovered except 1, who developed biliary cirrhosis while using preajmaline in conjunction with other hepatotoxic drugs.

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

We report the cases of 3 patients in whom ajmaline-induced acute hepatitis was followed by anicteric cholestasis persisting for more than 1 year after cessation of administration of the drug. Ajmaline was given for 8-16 days before the onset of acute hepatitis. Jaundice was preceded by fever, chills and abdominal pain, and was associated with hypereosinophilia. The initial lesions included centrilobular cholestasis and portal inflammatory infiltration. Jaundice lasted for 3 weeks to 11 months. In these 3 patients liver tests were still abnormal 17-26 months after ajmaline withdrawal; histological examination, performed 9-26 months after the onset of jaundice, showed a decreased number of interlobular bile ducts, ductular proliferation, and mild portal fibrosis; circulating immune complexes were demonstrated. These observations demonstrate that prolonged cholestasis can follow ajmaline-induced acute hepatitis. Persistence of cholestasis long after the withdrawal of ajmaline suggests some form of autoimmunity.

Topics: Acute Disease; Adult; Ajmaline; Antigen-Antibody Complex; Chemical and Drug Induced Liver Injury; Cholestasis; Estrogens; Female; Humans; Time Factors

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

A 75 year old man, treated with ajmaline, was admitted with malaise, fever, acute renal failure and cholestatic jaundice. Haemolytic anaemia and thrombocytopaenia were also found with a positive indirect Coomb's test in the presence of ajmaline. The immunological and haematological data are discussed in the light of previously published cases.

Topics: Aged; Ajmaline; Anemia, Hemolytic; Anuria; Cholestasis; Drug Hypersensitivity; Humans; Male; Thrombocytopenia

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

Topics: Ajmaline; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Humans; Middle Aged; Spironolactone

Topics: Ajmaline; Cholestasis; Female; Humans; Lymphatic Diseases; Middle Aged; Spironolactone

Topics: Aged; Ajmaline; Cholestasis; Female; Humans; Middle Aged

In two patients intrahepatic cholestasis and cholestatic liver disease probably due to N-propyl ajmaline were observed. In both cases there was a four-week-interval between the first ingestion of the drug and the onset of jaundice. In one case with rigors there was a temporary rise in temperature and cholestasis. In the other there was a two to three week prodromal period of pruritus and gastro-intestinal symptoms. Both cases were characterised by blood and pronounced tissue eosinophilia in the periportal zones, a marked increase of cholestatic and hepatic cell enzymes, serum bilirubin and cholesterol, a moderate increase in erythrocyte sedimentation rate and absence of leucocytosis. Pathological laboratory findings returned to normal spontaneously within 5 weeks in one case and within two weeks under steroid therapy in the other.

Topics: Adult; Ajmaline; Biopsy; Cholestasis; Eosinophilia; Female; Fever; Humans; Liver; Male; Pruritus; Time Factors

The authors report on four cases of immediate hepatotoxic reaction following diagnostic re-exposure. In checking 27 patients who had received NPAB treatment for the first time, four were found to have a hepatotoxic reaction that developed within 13--20 days after beginning the treatment. In view of the significance of NPAB for the treatment of cardiac rhythm disorders, further such studies are required in order to define the actual risk involved in this procedure.

Topics: Adult; Ajmaline; Antibodies; Arrhythmias, Cardiac; Bilirubin; Chemical and Drug Induced Liver Injury; Cholestasis; Eosinophils; Female; Humans; Kidney Tubules; Liver; Middle Aged; Muscle, Smooth; Thyroid Gland; Transaminases

Topics: Aged; Ajmaline; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Humans; Liver Cirrhosis, Biliary; Male; Methyltestosterone; Middle Aged; Xanthomatosis

Topics: Acute Disease; Ajmaline; Bile Ducts, Intrahepatic; Bilirubin; Cholestasis; Chronic Disease; Drug Synergism; Ethinyl Estradiol; Female; Humans; Liver; Liver Function Tests; Male; Methyltestosterone; Microscopy, Electron; Middle Aged; Mononuclear Phagocyte System; Plants, Medicinal; Rauwolfia