rifampin and Methemoglobinemia

At the present time there is no medicament completely harmless to the embryo or fetus. Passage through the placenta probably occurs by simple diffusion. Substances with a molecular weight under 600, low protein binding, a low degree of ionization and good solubility in lipids cross the placenta most easily. The harmful effects of the different groups of medicaments are describedand the substances classified into those not particularly toxic, those which can only be used in certain conditions and those only to be used in exceptional cases. The treatment of the most common infections in pregnancy is dealth with in detail. Infections of the maternal urinary tract and amnionitis raise most problems. For the treatment of amnionitis, direct instillation of the medicament into the amniotic sac is recommended.

Topics: Abortion, Spontaneous; Antimalarials; Antiviral Agents; Central Nervous System; Cephalosporins; DNA Replication; Female; Humans; Isoniazid; Maternal-Fetal Exchange; Methemoglobinemia; Molecular Weight; Nalidixic Acid; Pregnancy; Pregnancy Complications, Infectious; Protein Binding; Rifampin; Sulfonamides; Teratogens; Urinary Tract Infections

p-Chloroaniline is more potent at producing methemoglobin than aniline in animal models. This case highlights the clinical presentation of an inhalation exposure to p-chloroaniline and associated laboratory analysis. An in-vitro study evaluating the metabolism of p-chloroaniline in human hepatocytes was undertaken to evaluate the metabolic fate more closely.. A 20 year-old man was working at a chemical waste plant when he developed dizziness, abdominal pain, and nausea. The exam was remarkable for coma, tachycardia, cyanosis, and pulse oximetry of 75%. Arterial blood gases showed a pH 7.38, pCO(2) 41 mmHg, pO(2) 497 mmHg, bicarbonate 24 mEq/L and methemoglobin 69%. Methylene blue administration led to complete recovery without sequelae. p-Chloroaniline was later identified as the chemical involved. He denied direct contact with the chemical, but was not wearing a dust mask or respirator. GC/MS confirmed p-chloroaniline and metabolites in the patient's urine.. Human hepatocytes were incubated with 100 microM p-chloroaniline for 24 hours, in both rifampicin- and vehicle only-treated cells. The cell culture medium was collected for GC/MS analysis for p-chloroaniline metabolites.. Similar to the patient sample, both p-chloroaniline and p-chloroacetanilide were identified by GC/MS in hepatocytes incubated with p-chloroaniline. Neither p-chloroaniline incubated in empty cell culture nor direct GC/MS injection of p-chloroaniline generated any p-chloroacetanilide via non-enzymatic degradation.. The seemingly innocuous dermal and inhalation exposure to p-chloroaniline dust can lead to life-threatening methemoglobinemia. The diagnosis can be confirmed with GC/MS analysis of the patient's urine, searching for p-chloroaniline and its primary metabolite p-chloroacetanilide.

Topics: Abdominal Pain; Acetanilides; Air Pollutants; Aniline Compounds; Antidotes; Bicarbonates; Cells, Cultured; Clinical Laboratory Techniques; Coma; Cyanosis; Dizziness; Gas Chromatography-Mass Spectrometry; Hepatocytes; Humans; Inhalation Exposure; Male; Methemoglobin; Methemoglobinemia; Methylene Blue; Nausea; Occupational Exposure; Oximetry; Rifampin; Tachycardia; Toxicology; Young Adult

Dapsone (DDS) is useful in the treatment of a number of inflammatory conditions which are characterized by neutrophil infiltration. It is the drug of choice for the treatment of leprosy and prophylaxis of malaria. Haematological side effects of methaemoglobinaemia and haemolysis have been long recognized. However, the frequency and severity of these side effects in patients already treated with DDS as a single drug or as part of a multidrug therapy (MDT) have not been well documented. We report herein an investigation of the effect of dapsone long-term treatment on the haematological and biochemical alterations in leprosy patients undergoing dapsone as a single drug (DDS group) or as part of a multidrug therapy in combination with rifampin and clofazimine (MDT group). Methaemoglobinaemia and haemolytic anaemia were the principal side effects observed. Reticulocytes were found to be elevated (> 1.5%) in 90% of the patients. Heinz bodies were also detected (6.6% of the patients). The osmotic fragility test showed a reduction in cell resistance and in the evaluation of white cells a severe eosinophilia was found. Hepatic, pancreatic and renal evaluation by the determination of biochemical parameters showed rare and occasional changes of no apparent clinical significance. We conclude that haematological side effects of dapsone are significant even at doses currently used to treat leprosy (100 mg/day) and that rifampin and clofazimine do not increase the incidence of these effects during long-term treatment.

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Methemoglobinemia; Rifampin

We report clinical findings and pharmacokinetic data regarding a combined dapsone and clofazimine intoxication in a man, who ingested 50 tablets of dapsone (100 mg) 20 capsules of clofazimine (100 mg) and two tablets of rifampicin (600 mg). Oral administration of activated charcoal (50 grams) and sodium sulphate (20 grams) after gastric lavage resulted in an elimination half-life in plasma of 11.1 and 10.8 h for dapsone and its main metabolite, monoacetyldapsone, respectively. A rapid initial decrease of the plasma concentration of clofazimine was observed after gastric lavage and administration of activated charcoal and sodium sulphate. 15 h after this treatment, clofazimine plasma levels remained relatively constant. Dapsone-induced methaemoglobinaemia (48% at admission) was treated successfully with methylene blue.

Topics: Adult; Charcoal; Clofazimine; Dapsone; Drug Overdose; Gastric Lavage; Humans; Leprostatic Agents; Male; Methemoglobinemia; Methylene Blue; Rifampin; Suicide, Attempted; Sulfates

Topics: Aged; Antibiotics, Antitubercular; Humans; Male; Methemoglobinemia; Rifampin; Tuberculosis, Pulmonary