1. diuretics

2. From Knauf & Mutschler Klin. Wochenschr. 1991 69:239-250 70% 20% 5% 4.5% 0.5% Volume 1.5 L/day Urine Na 100 mEq/L Na Excretion 155 mEq/day 100% GFR 180 L/day Plasma Na 145 mEq/L Filtered Load 26,100 mEq/day CA Inhibitors Proximal tubule Loop Diuretics Loop of Henle Thiazides Distal tubule Antikaliuretics Collecting duct Thick Ascending Limb

5. N N SO 2 NH 2 SO 2 NH 2 NH 2 NH 2 NH 2 SO 2 NH 2 Cl Cl SO 2 NH 2 SO 2 NH 2 Cl SO 2 NH 2 N C N SO 2 Prontosil Sulfanilamide p-chlorobenzene sulfonamide 1,3 disulfonamide 6 cholrobenzene Cholrothiazide

7. General Structure of Thiazide Diuretics

8. Inhibition of high-affinity 3 H-metolazone binding by ions Data from Beaumont et. Al.: Thiazide diuretic drug receptors in rat kidney: identification with 3H]metolazone. Proc. Natl. Acad. Sci. USA 1988, 85:2311-2314. 112±5 Trisodium citrate 118±12 Dipotassium sulfate 152±22 Disodium sulfate 95±5 K acetate 82±5 Na acetate 12±2 KI 25±1 NaI 24±2 NaBr 36±7 Choline chloride 44±2 KCl 20±0.5 NaCl 4±1 LiCl 143±9 NaF % Control Ion

9. Correlation of the daily clinical doses of thiazide diuretics with their affinity for high-affinity 3 H-metolazone binding sites in rat kidney. Correlation coefficient r=0.7513. From Beaumont et al.: Thiazide diuretic drug receptors in rat kidney: identification with [ 3 H]metolazone. Proc. Natl. Acad. Sci. USA 1988, 85:2311-2314.

12. From Birkenhäger, WH: Diuretics and blood pressure reduction: physiological aspects. J. Hyperten. 1990, 8 (Suppl 2) S3-S7. Schematic drawing of temporal changes in mean arterial pressure (MAP), total peripheral vascular resistance (TPR), cardiac output (CO) and plasma volume (PV) during thiazide treatment of a hypertensive subject

13. From Birkenhäger, WH: Diuretics and blood pressure reduction: physiological aspects. J. Hyperten. 1990, 8 (Suppl 2) S3-S7.

14. From Birkenhäger, WH: Diuretics and blood pressure reduction: physiological aspects. J. Hyperten. 1990, 8 (Suppl 2) S3-S7.

20. From Martinez-Maldonado, M, and Cordova, HR: Cellular and molecular aspects of the renal effects of diuretic agents. Kidney Int. 1990, 38:632-641.

22. From Brater, DC. Pharmacodynamic considerations in the use of diuretics. Ann. Rev. Pharmacol. Toxicol 1983, 23:45-62.

24. From Brater, DC. Pharmacodynamic considerations in the use of diuretics. Ann. Rev. Pharmacol. Toxicol 1983, 23:45-62.

28. From Brater, DC. Pharmacology of Diuretics. Am. J. Med. Sci. 2000, 319:38-50. FE Na (%)

31. Maximum Doses of Loop Diuretics Data from Brater, DC. Pharmacology of Diuretics. Am. J. Med. Sci. 2000, 319:38-50. Oral intravenous Dose of furosemide (mg) Clinical Condition 160 80 Renal Insufficiency 0 < Cl Cr < 50 400 200 Renal Insufficiency Cl Cr < 20 240 120 Nephrotic Syndrome 80 40 Cirrhosis 80-160 40-80 Congestive Heart Failure