Effect of dichlorphenamide on gas exchange and CSF acid-base state in chronic respiratory failure.
Dichlorphenamide was administered to 13 patients with chronic respiratory failure, and the effects on gas exchange at rest and during exercise and on the acid-base state of CSF were observed. The ventilation for a given level of CO(2) production was increased both at rest and during exercise, resulting in an increased arterial Po(2) and decreased Pco(2).The ventilatory stimulation paralleled the development of a metabolic acidosis but was not associated with tissue CO(2) accumulation. Indeed, CSF Pco(2) and the oxygenated mixed venous (rebreathing) Pco(2) fell by the same amount as arterial Pco(2). The level of CO(2) elimination after two minutes of exercise was as great for a given work load after dichlorphenamide as before. These findings do not support the view that the drug impairs CO(2) transport from tissues either at rest or during exercise. They are most consistent with the view that the primary locus of action of dichlorphenamide in therapeutic doses is the kidney. The metabolic acidosis which results is likely the basis of the respiratory stimulatin, perhaps by its effects on the CSF H(2)CO(3)-HCO(3) - system. Inhibition of carbonic anhydrase in the red cell and choroid plexus are probably unimportant effects.
D000138:Acidosis / Q000209:etiology; D000368:Aged; D001784:Blood Gas Analysis; D001991:Bronchitis / Q000188:drug therapy*; D002245:Carbon Dioxide / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000187:drug effects*; D004005:Dichlorphenamide / Q000627:therapeutic use*; D005080:Exercise Test; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D012131:Respiratory Insufficiency / Q000188:drug therapy* / Q000503:physiopathology
D002245:Carbon Dioxide; D004005:Dichlorphenamide