Chlorpropamide toxicity with survival despite 27-day hypoglycemia.

CASE REPORT: In the past 5 years at our institution, 12 cases involving the ingestion of chlorpropamide 3-15 g were fatal. We report a 23-year-old woman with an estimated ingestion of chlorpropamide 5-10 g. Initial cardiovascular collapse, attributed to the blockade of potassium channel transport, responded to intensive support including 3 days of cardiac pacing. Urinary excretion of chlorpropamide and hypoglycemia persisted until day 27. The toxic mechanisms and high risk of chlorpropamide are summarized. A fatal therapeutic dose ratio as low as 4:1 has made this antidiabetic agent obsolete.

Effects of charcoal, sodium bicarbonate, and ammonium chloride on chlorpropamide kinetics.

The effects of activated charcoal, sodium bicarbonate, and ammonium chloride by mouth on chlorpropamide kinetics was studied in six healthy subjects. Activated charcoal, 50 gm, given immediately after 250 mg chlorpropamide reduced its absorption by 90%, but when given in repeated doses from 6 hr on (50 gm followed by 12.5 gm at 6-hr intervals) it did not shorten the chlorpropamide half-life (t 1/2). The t 1/2 of chlorpropamide was shortened from 49.7 +/- 7.4 to 12.8 +/- 1.1 hr by sodium bicarbonate and prolonged to 68.5 +/- 10.5 hr by ammonium chloride. The 72-hr urinary excretion of chlorpropamide was increased fourfold by alkalinization and decreased to 1/20 of baseline by acidification of the urine. The renal clearance of chlorpropamide correlated with urinary pH, ranging from 1 to 1000 ml/hr at the pH from 5 to 8. Urinary pH is likely to explain at least a part of great interindividual differences in the serum chlorpropamide concentrations during steady-state and variations in amount of urinary metabolites. In chlorpropamide intoxications activated charcoal can reduce absorption and alkalinization of the urine accelerates its elimination.