CO2 RETENTION AS A BASIS FOR INCREASED TOXICITY OF SALICYLATE WITH ACETAZOLAMIDE: AVOIDANCE OF INCREASED

LIDDELL, NORMAN E. AND THOMAS H. MAREN: CO2 retention as a basis for in-creased toxicity of salicylate with acetazolamide: Avoidance of increased toxicity with benzolamide. J. Pharmacol. Exp. Ther. 195: 1-7, 1975. Two carbonic anhydrase inhibitors, acetazolamide and benzolamide, are capable of in-creasing the toxicity of sodium salicylate in mice. Beginning at about 2 mg/kg, each of the inhibitors, in combination with a fixed (400 mg/kg) dose of salicylate, generates a dose-mortality curve that reaches a plateau at about 60 % deaths at 6 to 8 mg/kg. This effect can be duplicated by 8 to 10 % inspired CO2. It appears that the respiratory acidosis secondary to the inhibition of red cell carbonic anhydrase is responsible for the increased toxicity; earlier work by others shows that acidosis in’creases the con-centration of salicylate in the brain. In the treatment of salicylate poisoning by car-bonic anhydrase inhibitors, the goal is to alkalinize the urine and increase the excre-tion of salicylate. With the newer inhibitor, benzolamide, it is possible to dissociate the respiratory acidosis from the renal effect. Maximal alk.alinizatioh of the urine is possibl