diuretics and dehydrant drugs

Diuretics and dehydrant drugsDiuretics and dehydrant drugs

基础医学各论 II

The Kidney:The Kidney:•Excretion Excretion water, ions, and water, ions, and toxic toxic metabolitesmetabolites

BBAA

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

NaNa++, Cl, Cl －－ reabsorption in reabsorption in the kidneythe kidney

2525 ％％ NaNa++

65-7065-70 ％％ NaNa++

1010 ％％ NaNa++

Reabsorption sites Reabsorption sites of Naof Na++, K, K++, Cl, Cl--, and , and other ionsother ions

A. Diuretic drugsA. Diuretic drugs

•A diuretic is any substance influence the rates of transport of Na+, K+, Cl- ， HCO3

- and urate, increases urine and solute excretion.

Classification of diuretic drugsClassification of diuretic drugs

Loop diuretics-high efficacyfurosemide 呋塞米

thick ascending limb of Henle loopinhibiting Na+-K+-2Cl- symport

Thiazide diuretics moderate efficacyhydrochlorothiazide 氢氯噻嗪

distal convoluted tubuleinhibiting Na+-Cl- symport

K+-sparing diuretics low efficacyspironolactone 螺内酯

late distal tubule and collecting ductinhibiting renal epithelial Na+ channels


Furosemide Furosemide

呋塞米呋塞米

Bumetanide Bumetanide

布美他尼布美他尼

Etacrynic acidEtacrynic acid

依他尼酸依他尼酸


Loop diuretics

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.


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.


loop diuretics urine concentration

urine dilute

(2) Vasodilatation(2) Vasodilatation

Renal vasodilatation: renal blood flow Dilating veins: cardiac preload


2. Clinical uses2. Clinical uses

(1) Severe edema: ineffective by thiazides(1) Severe edema: ineffective by thiazides

(2) Acute pulmonary edema: heart failure(2) Acute pulmonary edema: heart failure

(3) Acute renal failure: combined with dopamine(3) Acute renal failure: combined with dopamine

(4) Hypercalcemia(4) Hypercalcemia

(5) Detoxication of toxins or drug overdose(5) Detoxication of toxins or drug overdose


3. Adverse effects3. Adverse effects

(1) Imbalance of water and electrolytes: (1) Imbalance of water and electrolytes:

acute hypovolumia; hypokalemia; acute hypovolumia; hypokalemia; etc.etc.

(2) Ototoxicity: hearing damage, contraindicated to combine (2) Ototoxicity: hearing damage, contraindicated to combine with aminoglycoside antibioticswith aminoglycoside antibiotics

(3) Other effects: GI reactions, hyperuricemia ((3) Other effects: GI reactions, hyperuricemia ( 尿酸增高尿酸增高 ),), arrhythmias, RAAS activity arrhythmias, RAAS activity , , etc.etc.


Other loop diuretic drugsOther loop diuretic drugs

Bumetanide Bumetanide 布美他尼布美他尼：： similar to furosemide, but less similar to furosemide, but less adverse effectsadverse effects

Torasemide Torasemide 托拉塞米：托拉塞米： stronger and longer actionsstronger and longer actions Etacrynic acid Etacrynic acid 依他尼酸：依他尼酸： weaker actions and more weaker actions and more

severe adverse effectssevere adverse effects


苄氟噻嗪苄氟噻嗪

氯噻嗪氯噻嗪

氢氯噻嗪氢氯噻嗪

氢氟噻嗪氢氟噻嗪

甲氯噻嗪甲氯噻嗪

泊利噻嗪泊利噻嗪

三氯噻嗪三氯噻嗪

Thiazide diuretic drugsThiazide 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


thiazides urine dilute

Used in treatment of mild and moderate edema in cardiac Used in treatment of mild and moderate edema in cardiac and renal diseases, and hepatic diseases with cautions;and renal diseases, and hepatic diseases with cautions;

Used in treatment of hypercalciuria and calcium oxalate Used in treatment of hypercalciuria and calcium oxalate stones in urinary tract.stones in urinary tract.

(2) Antihypertensive effects(2) Antihypertensive effects blood volume blood volume spasm responsiveness of arterial smooth muscles spasm responsiveness of arterial smooth muscles


(3) Diabetes insipidus ((3) Diabetes insipidus ( 尿崩症）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.


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.


Potassium-sparing diureticsPotassium-sparing diuretics

Spironolactone Spironolactone 螺内酯螺内酯 Triamterene Triamterene 氨苯喋啶氨苯喋啶 Amiloride Amiloride 阿米洛利阿米洛利


Spironolactone Spironolactone 螺内酯螺内酯

SpironolactoneSpironolactone AldosteroneAldosterone


Spironolactone 螺内酯

1. Pharmacological effects• Blocking aldosterone receptor• Decreasing Na+ reabsorption and K+ excretion • Weaker, slow acting, and lasting duration


Action of

spironolactone:

Blocking the effects of

aldosterone

spironolactone

2. Clinical uses2. Clinical uses Edema with increased aldosterone levlesEdema with increased aldosterone levles Combined with other diuretic drugsCombined with other diuretic drugs


(1) Hyperkalemia(1) Hyperkalemia

(2) Sex hormone-like effects(2) Sex hormone-like effects

(3) GI reactions(3) GI reactions

(4) CNS reactions(4) CNS reactions


triamterene triamterene amiloride amiloride


Triamterene Triamterene 氨苯喋啶氨苯喋啶Amiloride Amiloride 阿米洛利阿米洛利

1. Pharmacological effects1. Pharmacological effects Blocking renal epithelial NaBlocking renal epithelial Na++ channels: decreasing Na channels: decreasing Na++-K-K++

exchangeexchange

2. Clinical uses2. Clinical uses Similar to spironolactoneSimilar to spironolactone

3. Adverse effects3. Adverse effects Hyperkalemia, GI reactions, etc.Hyperkalemia, GI reactions, etc.


B. Dehydrant agents B. Dehydrant agents

Mannitol Mannitol 甘露醇甘露醇

OH OH OH OHOH OH OH OH

OH OHOH OH

Osmotic diureticsOsmotic diuretics

1. Pharmacological effects1. Pharmacological effects

(1) Dehydrant effects(1) Dehydrant effects

(2) Diuretic effects (osmotic diuretic effects)(2) Diuretic effects (osmotic diuretic effects)

2. Clinical uses2. Clinical uses

(1) Brain edema(1) Brain edema

(2) Glaucoma(2) Glaucoma

(3) Acute renal failure: prevention and early treatment(3) Acute renal failure: prevention and early treatment



(1) Elevated extracellular osmolality:(1) Elevated extracellular osmolality: pulmonary edema, etc.pulmonary edema, etc.

(2) Hyponatremia and dehydration:(2) Hyponatremia and dehydration: headache, nausea, headache, nausea, vomiting, etc.vomiting, etc.

• Contraindicated in anuric due to severe renal diseases, Contraindicated in anuric due to severe renal diseases, active cranial bleeding, heart failureactive cranial bleeding, heart failure


Other dehydrant drugsOther dehydrant drugs

Sorbitol Sorbitol 山梨醇山梨醇 Hypertonic glucose (50%) Hypertonic glucose (50%) 高渗葡萄糖高渗葡萄糖 Urea Urea 尿素尿素 Glycerin Glycerin 甘油甘油 Isosorbide Isosorbide 异山梨醇异山梨醇


diuretics and dehydrant drugs

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