Management of acid-base balance with red blood cell carbonic anhydrase (RCA). II. Control of acid-base balance with acetazolamide.
Acetazolamide, a carbonic anhydrase (CA) inhibitor, was used to normalize metabolic alkalemia. A dosage of acetazolamide for normalizing metabolic alkalemia has not yet been experimentally determined. The dosage of acetazolamide for this purpose is experimentally calculated in this paper. The correlation between various concentration of acetazolamide mixed with blood and the base excess (BE) levels in blood at the start of normalizing metabolic alkalosis was studied in vitro. The change rate of the BE level was calculated from BE levels noted before and after tonometry of the blood with and without acetazolamide. A dosage of acetazolamide which can cause the change rate of the BE level to decrease is considered to be an effective dosage. Metabolic alkalosis in vitro was produced by adding bicarbonate into the blood. An effective dosage of acetazolamide for metabolic alkalemia of which the BE range was from 0 to + 30 mEq/liter was calculated. CA activities in the kidney and the blood of dogs administered acetazolamide were examined. The effective dosage of acetazolamide obtained from in vitro experiments inhibited the CA activities not only in the blood but also in the kidneys. An effective dosage of acetazolamide to normalize a BE of + 10 mEq/liter in vitro was converted into about 7-12 mg/kg in vivo. This dosage inhibited the red blood cell carbonic anhydrase (RCA) activity to 20-40%, whereas the normal physiological variation range is 25%. An effective dosage of acetazolamide in the blood did not proportionally increase with an increase of HCO3- during severe alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)
D000086:Acetazolamide / Q000494:pharmacology / Q000627:therapeutic use*; D000471:Alkalosis / Q000188:drug therapy*; D000818:Animals; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology
D002256:Carbonic Anhydrases; D000086:Acetazolamide