DOC for lithium induced Nephrogenic Diabetes Insipidus

AMILORIDE Mechanism of action:- The luminal membrane of late DT and CD cells expresses a distinct 'renal epithelial' or 'amiloride sensitive' Na+ channel through which Na+ enters the cell down its electrochemical gradient which is generated by Na+K+ ATPase operating at the basolateral membrane. This Na+ entry paially depolarizes the luminal membrane creating a -15 mV transepithelial potential difference which promotes secretion of K+ into the lumen through K+ channels. Though there is no direct coupling between Na+ and K+ channels, more the delivery of Na+ to the distal nephron--greater is its entry through the Na+ channel--luminal membrane is depolarized to a greater extent--driving force for K+ secretion is augmented. As such, all diuretics acting proximally (loop diuretics, thiazides, CAse inhibitors) promote K+ secretion. Amiloride and triamterene block the luminal Na+ channels and indirectly inhibit K+ excretion( Pottasium sparing diuretic). side effects:- Nausea, diarrhoea and headache. Uses:- Amiloride blocks entry of Li+ through Na+ channels in the CD cells and mitigates diabetes insipidus induced by lithium. Given as an aerosol it affords symptomatic improvement in cystic fibrosis by increasing fluidity of respiratory secretions. Ref:- kd tripathi; pg num:-589,590