Isoniazid overdose: four case reports and review of the literature.

OBJECTIVES: To review the pathophysiology, presentation and treatment of isoniazid (INH) intoxication. DATA SOURCES: Human, animal and modeling studies published since 1940 identified through MEDLINE and a review of the bibliographies of relevant articles. STUDY SELECTION AND DATA EXTRACTION: The studies identified were reviewed with emphasis on the most recent. Earlier studies were selected for their historical value and relevance to the clinical setting. DATA SYNTHESIS: Isoniazid overdose is a potentially fatal intoxication. The incidence of tuberculosis has recently increased in the United States and therefore the frequency of INH overdose may also increase. Patients with INH overdose may present with nausea, vomiting, ataxia, symptoms reminiscent of atropine intoxication, coma and grand mal seizures. Lactic acidosis is revealed by laboratory evaluation. Treatment requires admission to the ICU for ventilatory support, and management of seizures and acid-base abnormalities. Pyridoxine, in a dose equivalent to the amount of INH ingested, is the only effective antidote. CONCLUSIONS: INH overdose should be suspected in any patient presenting with seizures and metabolic acidosis. Prognosis is good when treatment is instituted early.

Tolerance of volunteers to cyclosporine A-dilauroylphosphatidylcholine liposome aerosol.

Cyclosporine A (CsA) in liposomes of dilauroylphosphatidylcholine (DLPC), containing 118 micrograms of CsA/L of aerosol with a particle size of 1.6 to 1.7 micron diameter, was inhaled by 10 nonsmoking, normal volunteers each for 45 min. Aerosol was administered through an Aerotech II nebulizer (CIS-US, Inc., Bedford, MA) mouthpiece. Eight of the 10 volunteers had tracheal irritation and intermittent coughing following exposure. FEV1 and FVC values were mildly reduced, but returned to normal in 1 h. Blood chemical and hematologic values were unchanged at any time point after as opposed to before inhalation. Nine of the 10 volunteers later inhaled DLPC only, administered through the nebulizer mouthpiece. There was no change in FEV1 or FVC values, and there was no coughing or tracheal irritation. Subsequently, five of the volunteers who had previously had respiratory reactions inhaled CsA-DLPC liposome aerosol for 45-min, but through a mouth-only face mask. There was no tracheal irritation, coughing, or changes in spirometric measures. Blood concentrations of CsA at 15 min after the 45-min inhalation with a face mask averaged 83 +/- 42 ng/ml (mean +/- SD). At 24 h after treatment, CsA was undetectable in blood of the initial 10 volunteers. These studies indicate that CsA-DLPC liposome aerosol can be safely explored as a treatment for patients with moderately severe asthma.