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Diuretics and dehydrant drugs

基础医学各论 II. Diuretics and dehydrant drugs. The Kidney: Excretion water, ions, and toxic metabolites. A. B. Renal structures for urine generation (A) and osmotic gradient (B). 10 ％ Na +. 65-70 ％ Na +. Na + , Cl － reabsorption in the kidney. 25 ％ Na +.

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Diuretics and dehydrant drugs

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  1. 基础医学各论II Diuretics and dehydrant drugs

  2. The Kidney: • Excretion water, ions, and toxic metabolites

  3. A B Renal structures for urine generation (A) and osmotic gradient (B)

  4. 10％Na+ 65-70％Na+ Na+, Cl－reabsorption in the kidney 25％Na+

  5. Reabsorption sites of Na+, K+, Cl-, and other ions

  6. A. Diuretic drugs • A diuretic is any substance influence the rates of transport of Na+, K+, Cl-，HCO3- and urate, increases urine and solute excretion.

  7. A. Diuretic drugs

  8. A. Diuretic drugs Loop diuretics Furosemide 呋塞米 Bumetanide 布美他尼 Etacrynic acid 依他尼酸

  9. A. Diuretic drugs Furosemide 速尿 1. Pharmacological effects (1) Diuretic effects • Inhibiting the Na+-K+-2Cl- cotransporter （symport) of the luminal membrane in the thick portion of the ascending limb of the loop of Henle, and reducing the reabsorption of Na+, K+ and Cl-. • Most efficacious among the diuretic drugs, because the ascending limb accounts for the reabsorption of 25-30% of filtered NaCl and downstream sies are not able to compensate for this increased Na+ load.

  10. A. Diuretic drugs • Blocking kidney’s ability to concentrate urine during hydropenia, by decreasing the hypertonic medullary interstitium. • Impairing kidney’s ability to excrete a dilute urine. • Also, increasing excretion of Ca2+, Mg2+ by abolition of transepithelial potential difference.

  11. urine dilute loop diuretics urine concentration

  12. A. Diuretic drugs • (2) Vasodilatation • Renal vasodilatation: renal blood flow  • Dilating veins: cardiac preload 

  13. A. Diuretic drugs 2. Clinical uses (1) Severe edema: ineffective by thiazides (2) Acute pulmonary edema: heart failure (3) Acute renal failure: combined with dopamine (4) Hypercalcemia (5) Detoxication of toxins or drug overdose

  14. A. Diuretic drugs 3. Adverse effects (1) Imbalance of water and electrolytes: acute hypovolumia; hypokalemia; etc. (2) Ototoxicity: hearing damage, contraindicated to combine with aminoglycoside antibiotics (3) Other effects: GI reactions, hyperuricemia (尿酸增高), arrhythmias, RAAS activity , etc.

  15. A. Diuretic drugs • Other loop diuretic drugs • Bumetanide 布美他尼：similar to furosemide, but less adverse effects • Torasemide 托拉塞米：stronger and longer actions • Etacrynic acid 依他尼酸：weaker actions and more severe adverse effects

  16. A. Diuretic drugs Thiazidediuretic drugs 苄氟噻嗪 氯噻嗪 氢氯噻嗪 氢氟噻嗪 甲氯噻嗪 泊利噻嗪 三氯噻嗪

  17. A. Diuretic drugs • Thiazide diuretic drugs • 1. Pharmacological effects and clinical uses • (1) Diuretic effects • Acting on distal convoluted tubule, inhibiting Na+-Cl- cotransporter (symport) • Decreasing kidney’s ability to dilute urine • Increasing the excretion of Na+, Cl-, K+, Mg2+, HCO3-, but increasing the reabsorption of Ca2+ in distal convoluted tubule

  18. thiazides urine dilute

  19. A. Diuretic drugs • Used in treatment of mild and moderate edema in cardiac and renal diseases, and hepatic diseases with cautions; • Used in treatment of hypercalciuria and calcium oxalate stones in urinary tract. • (2) Antihypertensive effects • blood volume  • spasm responsiveness of arterial smooth muscles 

  20. A. Diuretic drugs • (3) Diabetes insipidus (尿崩症） • Unique ability to produce a hyperosmolar urine, and can substitute for the antidiuretic hormone in the treatment of nephrogenic diabetes insipidus. • The urine volume of such individuals may drop from 11 L/day to 3 L/day when treated with the drug.

  21. A. Diuretic drugs 2. Adverse effects (1) Imbalance of eletrolytes hypokalemia hypomagnesemia hyponatremia hypochloremia cautions: dose individualization, K+ supplement (2) Dysfunctio of metabolism hyperglycemia hyperlipidemia hyperuricemia contraindicated in diabetes and gout patients (3) Hypersensitivity bone marrow supression, dermatitis, necrotizing vasculitis, interstitial nephritis, etc.

  22. A. Diuretic drugs Potassium-sparing diuretics Spironolactone 螺内酯 Triamterene 氨苯喋啶 Amiloride 阿米洛利

  23. A. Diuretic drugs Spironolactone 螺内酯 Spironolactone Aldosterone

  24. A. Diuretic drugs • Spironolactone 螺内酯 • 1. Pharmacological effects • Blocking aldosterone receptor • Decreasing Na+ reabsorption and K+ excretion • Weaker, slow acting, and lasting duration

  25. Action of spironolactone: Blocking the effects of aldosterone

  26. spironolactone

  27. A. Diuretic drugs 2. Clinical uses • Edema with increased aldosterone levles • Combined with other diuretic drugs 3. Adverse effects (1) Hyperkalemia (2) Sex hormone-like effects (3) GI reactions (4) CNS reactions

  28. A. Diuretic drugs Triamterene 氨苯喋啶 Amiloride 阿米洛利 triamterene amiloride

  29. A. Diuretic drugs 1. Pharmacological effects • Blocking renal epithelial Na+ channels: decreasing Na+-K+ exchange 2. Clinical uses • Similar to spironolactone 3. Adverse effects • Hyperkalemia, GI reactions, etc.

  30. B. Dehydrant agents Osmotic diuretics Mannitol 甘露醇 OH OH OH OH OH OH

  31. B. Dehydrant agents 1. Pharmacological effects (1) Dehydrant effects (2) Diuretic effects (osmotic diuretic effects) 2. Clinical uses (1) Brain edema (2) Glaucoma (3) Acute renal failure: prevention and early treatment

  32. B. Dehydrant agents • 3. Adverse effects • (1) Elevated extracellular osmolality:pulmonary edema, etc. • (2) Hyponatremia and dehydration:headache, nausea, vomiting, etc. • Contraindicated in anuric due to severe renal diseases, active cranial bleeding, heart failure

  33. B. Dehydrant agents • Other dehydrant drugs • Sorbitol 山梨醇 • Hypertonic glucose (50%) 高渗葡萄糖 • Urea 尿素 • Glycerin 甘油 • Isosorbide 异山梨醇

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