UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

利尿剂的作用机制

Author
D Craig Brater, MD
Section Editors
Richard H Sterns, MD
Michael Emmett, MD
Deputy Editor
John P Forman, MD, MSc
Translators
王蔚东, 教授

引言

利尿剂是最常用的药物之一。这类药物通过减少肾单位不同部位对钠的重吸收，从而增加尿液中钠和水的丢失。利尿剂能引起机体液体的负平衡，所以有助于治疗各种情况，尤其是水肿状态和高血压。

利尿剂的机制及其作用的时间进程的概述见此专题。利尿剂的用法用量和不良反应将单独讨论。 (参见“袢利尿剂：最大有效剂量和主要副作用”和“袢利尿剂与噻嗪类利尿剂诱导的电解质并发症的时间进程”)

作用机制

根据减少钠重吸收的部位的不同，利尿剂通常被分为四大类[1,2]：

●袢利尿剂，作用于亨利(Henle)袢升支粗段

●噻嗪类利尿剂，作用于远端小管和连结管(以及可能作用于皮质集合管初始段)

         

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: 2017-06 . | This topic last updated: 2017-06-05.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Rose BD. Diuretics. Kidney Int 1991; 39:336.
  2. Hropot M, Fowler N, Karlmark B, Giebisch G. Tubular action of diuretics: distal effects on electrolyte transport and acidification. Kidney Int 1985; 28:477.
  3. Katz AI. Distribution and function of classes of ATPases along the nephron. Kidney Int 1986; 29:21.
  4. Wright FS. Flow-dependent transport processes: filtration, absorption, secretion. Am J Physiol 1982; 243:F1.
  5. Greger R, Velázquez H. The cortical thick ascending limb and early distal convoluted tubule in the urinary concentrating mechanism. Kidney Int 1987; 31:590.
  6. Ellison DH, Velázquez H, Wright FS. Adaptation of the distal convoluted tubule of the rat. Structural and functional effects of dietary salt intake and chronic diuretic infusion. J Clin Invest 1989; 83:113.
  7. Stanton BA, Kaissling B. Regulation of renal ion transport and cell growth by sodium. Am J Physiol 1989; 257:F1.
  8. Scherzer P, Wald H, Popovtzer MM. Enhanced glomerular filtration and Na+-K+-ATPase with furosemide administration. Am J Physiol 1987; 252:F910.
  9. Loon NR, Wilcox CS, Unwin RJ. Mechanism of impaired natriuretic response to furosemide during prolonged therapy. Kidney Int 1989; 36:682.
  10. Stanton BA, Kaissling B. Adaptation of distal tubule and collecting duct to increased Na delivery. II. Na+ and K+ transport. Am J Physiol 1988; 255:F1269.
  11. Hebert SC, Reeves WB, Molony DA, Andreoli TE. The medullary thick limb: function and modulation of the single-effect multiplier. Kidney Int 1987; 31:580.
  12. O'Grady SM, Palfrey HC, Field M. Characteristics and functions of Na-K-Cl cotransport in epithelial tissues. Am J Physiol 1987; 253:C177.
  13. Amsler K, Kinne R. Photoinactivation of sodium-potassium-chloride cotransport in LLC-PK1/Cl 4 cells by bumetanide. Am J Physiol 1986; 250:C799.
  14. Bronner F. Renal calcium transport: mechanisms and regulation--an overview. Am J Physiol 1989; 257:F707.
  15. Friedman PA. Basal and hormone-activated calcium absorption in mouse renal thick ascending limbs. Am J Physiol 1988; 254:F62.
  16. Hufnagle KG, Khan SN, Penn D, et al. Renal calcifications: a complication of long-term furosemide therapy in preterm infants. Pediatrics 1982; 70:360.
  17. Short A, Cooke RW. The incidence of renal calcification in preterm infants. Arch Dis Child 1991; 66:412.
  18. Velázquez H, Wright FS. Effects of diuretic drugs on Na, Cl, and K transport by rat renal distal tubule. Am J Physiol 1986; 250:F1013.
  19. Kunau RT Jr, Weller DR, Webb HL. Clarification of the site of action of chlorothiazide in the rat nephron. J Clin Invest 1975; 56:401.
  20. Plotkin MD, Kaplan MR, Verlander JW, et al. Localization of the thiazide sensitive Na-Cl cotransporter, rTSC1 in the rat kidney. Kidney Int 1996; 50:174.
  21. Shimizu T, Yoshitomi K, Nakamura M, Imai M. Site and mechanism of action of trichlormethiazide in rabbit distal nephron segments perfused in vitro. J Clin Invest 1988; 82:721.
  22. Terada Y, Knepper MA. Thiazide-sensitive NaCl absorption in rat cortical collecting duct. Am J Physiol 1990; 259:F519.
  23. Rouch AJ, Chen L, Troutman SL, Schafer JA. Na+ transport in isolated rat CCD: effects of bradykinin, ANP, clonidine, and hydrochlorothiazide. Am J Physiol 1991; 260:F86.
  24. Leviel F, Hübner CA, Houillier P, et al. The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. J Clin Invest 2010; 120:1627.
  25. Garg LC, Narang N. Effects of hydrochlorothiazide on Na-K-ATPase activity along the rat nephron. Kidney Int 1987; 31:918.
  26. Stanton BA. Cellular actions of thiazide diuretics in the distal tubule. J Am Soc Nephrol 1990; 1:832.
  27. Tran JM, Farrell MA, Fanestil DD. Effect of ions on binding of the thiazide-type diuretic metolazone to kidney membrane. Am J Physiol 1990; 258:F908.
  28. Hoover RS, Poch E, Monroy A, et al. N-Glycosylation at two sites critically alters thiazide binding and activity of the rat thiazide-sensitive Na(+):Cl(-) cotransporter. J Am Soc Nephrol 2003; 14:271.
  29. Boer WH, Koomans HA, Dorhout Mees EJ. Acute effects of thiazides, with and without carbonic anhydrase inhibiting activity, on lithium and free water clearance in man. Clin Sci (Lond) 1989; 76:539.
  30. Sutton RA. Disorders of renal calcium excretion. Kidney Int 1983; 23:665.
  31. Costanzo LS. Localization of diuretic action in microperfused rat distal tubules: Ca and Na transport. Am J Physiol 1985; 248:F527.
  32. Gesek FA, Friedman PA. Mechanism of calcium transport stimulated by chlorothiazide in mouse distal convoluted tubule cells. J Clin Invest 1992; 90:429.
  33. Nijenhuis T, Hoenderop JG, Loffing J, et al. Thiazide-induced hypocalciuria is accompanied by a decreased expression of Ca2+ transport proteins in kidney. Kidney Int 2003; 64:555.
  34. Frindt G, Sackin H, Palmer LG. Whole-cell currents in rat cortical collecting tubule: low-Na diet increases amiloride-sensitive conductance. Am J Physiol 1990; 258:F562.
  35. Sansom S, Muto S, Giebisch G. Na-dependent effects of DOCA on cellular transport properties of CCDs from ADX rabbits. Am J Physiol 1987; 253:F753.
  36. Kleyman TR, Cragoe EJ Jr. The mechanism of action of amiloride. Semin Nephrol 1988; 8:242.
  37. Horisberger JD, Giebisch G. Potassium-sparing diuretics. Ren Physiol 1987; 10:198.
  38. Abdallah JG, Schrier RW, Edelstein C, et al. Loop diuretic infusion increases thiazide-sensitive Na(+)/Cl(-)-cotransporter abundance: role of aldosterone. J Am Soc Nephrol 2001; 12:1335.
  39. Batlle DC, von Riotte AB, Gaviria M, Grupp M. Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy. N Engl J Med 1985; 312:408.
  40. Sica DA, Gehr TW. Triamterene and the kidney. Nephron 1989; 51:454.
  41. Fairley KF, Woo KT, Birch DF, et al. Triamterene-induced crystalluria and cylinduria: clinical and experimental studies. Clin Nephrol 1986; 26:169.
  42. Carr MC, Prien EL Jr, Babayan RK. Triamterene nephrolithiasis: renewed attention is warranted. J Urol 1990; 144:1339.
  43. Farge D, Turner MW, Roy DR, Jothy S. Dyazide-induced reversible acute renal failure associated with intracellular crystal deposition. Am J Kidney Dis 1986; 8:445.
  44. Weinberg MS, Quigg RJ, Salant DJ, Bernard DB. Anuric renal failure precipitated by indomethacin and triamterene. Nephron 1985; 40:216.
  45. Woolfson RG, Mansell MA. Does triamterene cause renal calculi? BMJ 1991; 303:1217.
  46. LEAF A, SCHWARTZ WB, RELMAN AS. Oral administration of a potent carbonic anhydrase inhibitor (diamox). I. Changes in electrolyte and acid-base balance. N Engl J Med 1954; 250:759.
  47. Preisig PA, Toto RD, Alpern RJ. Carbonic anhydrase inhibitors. Ren Physiol 1987; 10:136.
  48. Seely JF, Dirks JH. Micropuncture study of hypertonic mannitol diuresis in the proximal and distal tubule of the dog kidney. J Clin Invest 1969; 48:2330.
  49. Mathisen O, Raeder M, Kiil F. Mechanism of osmotic diuresis. Kidney Int 1981; 19:431.
  50. GIPSTEIN RM, BOYLE JD. HYPERNATREMIA COMPLICATING PROLONGED MANNITOL DIURESIS. N Engl J Med 1965; 272:1116.
  51. Aviram A, Pfau A, Czaczkes JW, Ullmann TD. Hyperosmolality with hyponatremia, caused by inappropriate administration of mannitol. Am J Med 1967; 42:648.
  52. Wilcox CS, Guzman NJ, Mitch WE, et al. Na+, K+, and BP homeostasis in man during furosemide: effects of prazosin and captopril. Kidney Int 1987; 31:135.
  53. Wilcox CS, Mitch WE, Kelly RA, et al. Response of the kidney to furosemide. I. Effects of salt intake and renal compensation. J Lab Clin Med 1983; 102:450.
  54. Ram CV, Garrett BN, Kaplan NM. Moderate sodium restriction and various diuretics in the treatment of hypertension. Arch Intern Med 1981; 141:1015.
  55. Liu FY, Cogan MG. Angiotensin II: a potent regulator of acidification in the rat early proximal convoluted tubule. J Clin Invest 1987; 80:272.
  56. Stanton BA. Regulation of Na+ and K+ transport by mineralocorticoids. Semin Nephrol 1987; 7:82.
  57. Osborn JL, Holdaas H, Thames MD, DiBona GF. Renal adrenoceptor mediation of antinatriuretic and renin secretion responses to low frequency renal nerve stimulation in the dog. Circ Res 1983; 53:298.
  58. Guyton AC. Blood pressure control--special role of the kidneys and body fluids. Science 1991; 252:1813.
  59. Mizelle HL, Montani JP, Hester RL, et al. Role of pressure natriuresis in long-term control of renal electrolyte excretion. Hypertension 1993; 22:102.
  60. Bock HA, Stein JH. Diuretics and the control of extracellular fluid volume: role of counterregulation. Semin Nephrol 1988; 8:264.
  61. Dirks JH, Cirksena WJ, Berliner RW. Micropuncture study of the effect of various diuretics on sodium reabsorption by the proximal tubules of the dog. J Clin Invest 1966; 45:1875.
  62. Nomura A, Yasuda H, Minami M, et al. Effect of furosemide in congestive heart failure. Clin Pharmacol Ther 1981; 30:177.
  63. Maronde RF, Milgrom M, Vlachakis ND, Chan L. Response of thiazide-induced hypokalemia to amiloride. JAMA 1983; 249:237.
  64. Rudy DW, Voelker JR, Greene PK, et al. Loop diuretics for chronic renal insufficiency: a continuous infusion is more efficacious than bolus therapy. Ann Intern Med 1991; 115:360.
  65. Ikram H, Chan W, Espiner EA, Nicholls MG. Haemodynamic and hormone responses to acute and chronic frusemide therapy in congestive heart failure. Clin Sci (Lond) 1980; 59:443.
  66. Morgan DB, Davidson C. Hypokalaemia and diuretics: an analysis of publications. Br Med J 1980; 280:905.
  67. Ridgeway NA, Ginn DR, Alley K. Outpatient conversion of treatment to potassium-sparing diuretics. Am J Med 1986; 80:785.