Diuretic

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Diuretics are "agents that promote the excretion of urine through their effects on kidney function."^[1]

Physiology of sodium reabsorption in the kidney[edit]

Classification[edit]

Carbonic anhydrase inhibitors[edit]

Carbonic anhydrase inhibitors are a "class of compounds that reduces the secretion of h+ ions by the proximal kidney tubule through inhibition of carbonic anhydrases."^[2][3]

Osmotic diuretic[edit]

Osmotic diuretics are "compounds that increase urine volume by increasing the amount of osmotically active solute in the urine. Osmotic diuretics also increase the osmolarity of plasma."^[4]

Loop diuretics[edit]

More formally called sodium potassium chloride symporter inhibitors, these are agents that inhibit sodium-potassium-chloride symporters in the thick ascending limb at the junction of the Loop of Henle and distal kidney tubules.^[5]

A meta-analysis concluded that "administering furosemide as a continuous infusion for greater diuresis and reduction in total body weight in patients hospitalized with ADHF". ^[6]

Thiazides[edit]

Thiazides are "heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters."^[7] Examples include hydrochlorothiazide and chlorthalidone.

Regarding effectiveness, a systematic review by the Cochrane Collaboration found:^[8]

• Chlorthalidone's reduces systolic and diagnostic blood pressure by 12.0/4 mmHg and the reduction is not dose related when tested at a range of doses from 12.5 mg to 75 mg/day.
• Hydrochlorothiazide's effect is dose related and at a maximum dose of 50 mg/day, the reduction is 11 mmHg/5 mmHg.

Chlorthalidone may be the best choice based on the Multiple Risk Factor Intervention Trial^[9] and other studies.^[10][11][12] In the MRFIT trial, the clinics that predominantly used chlorthalidone reported lower mortality than the clinics using hydrochlorothiazide (5% versus 7%).

Regarding chlorthalidone versus calcium channel blockers:

• "Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive" according to a randomized controlled trial that compared to . ^[13]
• "Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone" according to an unblinded randomized controlled trial^[14]
• "In elderly patients with isolated systolic hypertension, administration of lacidipine or chlorthalidone markedly reduced systolic blood pressure with no difference in the incidence of cardiovascular events and total mortality." according to an unblinded randomized controlled trial. ^[15]

Potassium-sparing diuretics[edit]

These work in the collecting duct and late distal convoluted tubule either by inhibiting mineralacorticoids receptors or by blocking the epithelial sodium channel.^[16][17] Amiloride is beter tolerated than triamterene. Their ability to treat hypertension is doubtful.^[18]

Vasopressin antagonists[edit]

Tolvaptan, a vasopressin antagonist, may be beneficial according to a randomized controlled trial.^[19][20] Tolvaptan is a selective cell surface receptors V2 antagonist in the distal nephron which causes loss of free water.^[21] Other vasopressin antagonists act mainly on V1a cell surface receptors.

Brain (B-type) natriuretic peptide[edit]

Nesiritide, a brain (B-type) natriuretic peptide, may help patients with decompensated congestive heart failure according to a randomized controlled trial.^[22] Natriuretic peptide causes diuresis, vasodilitation, and suppression of the renin-angiotensin system and sympathetic nervous system.^[22]

Medical uses[edit]

Diuretics may be used to treat hypertension, heart failure, and other illnesses.^[23] Occasionally high doses or combinations of diuretics are needed.^{[23][24][25][26]}

Adverse effects[edit]

Many diuretics, aimed at sodium and water retention, may reduce potassium to dangerous levels. In addition to monitoring, it may be necessary, for example, to combine thiazide diuretics with supplemental potassium or potassium-sparing diuretics.

Hydrochlorothiazide at doses above 25 mg per day may be associated with sudden cardiac death.^[27] This risk may be reduced by adding a potassium-sparing diuretic.^[27]

References[edit]