【正文】 titial fluid H2O diluted Parathormone calcitriol Na+/Cl symporter 10 Reabsorption of tubules and collecting tubes ? late distal tubules and collecting tubules ? Na+/K+ exchange ? reabsorption of Na+ and its coupled secretion of K+ is regulated by aldosterone ? absorption of water is regulated by antidiuretic hormone (ADH) ?Promotes collecting tubules permeable to water ?modulates the concentration of final urine 11 spironolactone Triamterene amiloride lumennegative electrical potential ?all these agents are K+sparing diuretics 12 Classification of Diuretics ? High efficacy diuretics ? Moderate efficacy diuretics ? Low efficacy diuretics 13 Classification of Diuretics ? High efficacy diuretics ? Moderate efficacy diuretics ? Low efficacy diuretics 14 High efficacy diuretics ? Furosemide, bumetanide, ethacrynic acid ? have their major action on the ascending limb of the loop of Henle —— loop diuretics 15 Pharmacokiics ? absorbed rapidly by oral administration. Bioavailability is 5070%. ? If given iv, the effects of furosemide response within 5 mins, duration time 23 hrs. ? 5060 L of urine excretion within 24 hours after using large doses of furosemide. ? Protein binding rate is 95%. ? t1/2 1 hr, which may be prolonged to 10 hr in renal dysfunction. 16 Mechanism of action ? inhibit the Na+/K+/2Cl cotransporter in the thick ascending limb of the loop of Henle ? reabsorption of Na+, Cl, Ca2+ and Mg2+ are decreased ? secretion of K+ is increased ? the most efficacious of the diuretic drugs ? the ascending limb accounts for the reabsorption of 25%30% of filtered NaCl ? downstream sites are not able to pensate for this increased Na+ load 17 1 2 4 5 3 apical membrane Basolateral membrane Na+/K+/2Cl cotransport system lumenpositive electrical potential H2O diluted Loop diuretics (furosemide) Na+K+ATPase interstitial fluid 18 Pharmacological effects ? Diuretic activity ? Diuretic activity is rapid, strong and short ? Large amounts of Na+, Cl, K+, Ca2+ and Mg2+ are excreted and Cl loss is more than Na+ in urine Relative changes in the position of urine induced by loop diuretics 19 Pharmacological effects ? Decrease renal vascular resistance, increase renal blood flow ? redistribution of blood flow within the renal cortex ? Increase renin release ? large volume depletion reflexly activate the sympathetic nervous system and stimulate the intrarenal baroreceptor mechanism ? induces renal prostaglandins synthesis in the kidney 20 Pharmacological effects ? Relieve pulmonary congestion and reduce left ventricular filling pressures ? increase systemic venous capacitance in congestive heart failure patient ? Inhibit electrolyte transport in inner ear ?