Disturbances of electrolyte excretion caused by folic acid analoga

The antibiotic antagonists of folic acid trimethoprim, tetroxoprim, pyrimet hamine and their antiinflammatory and antineoplastic analog methotrexate ha ve structural characteristics in common with the potassium-sparing diuretic triamterene. They may, therefore, share with triamterene potassium-sparing renal effects. Clearance studies performed on anesthetized male Sprague Da wley rats have shown that trimethoprim and tetroxoprim injected intravenous ly induce dose-dependently natriuretic and antikaliuretic effects whereas p yrimethamine and methotrexate do not affect urinary sodium and potassium ex cretion. The structurally related anti-protozoal compound pentamidine also evokes an antikaliuretic effect. In contrast to trimethoprim and tetroxopri m, with pentamidine the antikaliuretic is accompanied by a marked decrease of urinary sodium and chloride excretion. At higher doses, pentamidine in t hese experiments induces a pronounced fall of the glomerular filtration rat e which is thought to be an important factor in the antikaliuretic effect o f this drug. Trimethoprim and tetroxoprim share with potassium-sparing diur etics natriuretic and antikaliuretic renal effects which may be caused by s imilar mechanisms in the distal nephron whereas pyrimthamine and methotrexa te do not.