Diuretics: Types, Sites of Action, and Clinical Uses in Hypertension and Edema

What is diuresis?

An increase in urine volume.

What is natriuresis?

An increase in renal sodium excretion.

List the clinical uses of diuretics.

Hypertension, Edema, Congestive Heart Failure (CHF), Kidney Disease, Hepatic Cirrhosis, Hypercalcemia, Diabetes Insipidus

What is the action of Acetazolamide?

Decreases NaHCO3 reabsorption and H2O reabsorption; metabolic acidosis

What are the clinical uses of Acetazolamide?

Acute Mountain Sickness, Metabolic Alkalosis, Glaucoma, Urinary Alkalinization

What are the toxicities associated with Acetazolamide?

Hyperchloremic metabolic acidosis, renal stones, renal potassium wasting, drowsiness/ paresthesia

What is the mechanism of action of loop diuretics? (used in edema)

• Inhibit the Na+/K+/2Cl- cotransporter in the thick ascending limb

•Reduce NaCl, K+, and divalent cation (Ca2+ and Mg2+) reabsorption

•Increase renal blood flow

•Rapid response after I.V. administration

Name loop diuretics

Furosemide, bumetanide, ethacrynic acid

What are the toxicities of loop diuretics?

Dehydration, hypokalemic metabolic alkalosis, ototoxicity, hyperuricemia, hypomagnesemia

CI: sulfa allergies

What is the action of thiazide diuretics?

• Inhibit NaCl reabsorption in the distal convoluted tubule.

• Enhance Ca2+ reabsorption in kidney

•May open Ca2+ -activated K+ channels leading to vasodilation

•Decrease in peripheral resistance may result from negative Na+ balance

List thiazide-like diuretics

•Chlorthalidone

•Indapamide

•Metolazone

What are common toxicities of thiazide diuretics?

•Hypokalemia

•Hypokalemic metabolic alkalosis

•Hyperuricemia

•Hypercalcemia

•Impaired carbohydrate tolerance

•Hyperlipidemia

•Hyponatremia

•Erectile dysfunction

What is the action of potassium-sparing diuretics like Amiloride and Triamterene?

Inhibit Na+ channels in the apical membrane of the collecting tubule; reduced Na+ entry into these cells also reduces K+ excretion (K+ sparing)

What are the contraindications for Amiloride? For Triamterene?

Potassium supplements and ACE inhibitors; both and kidney stones

What is the action of Spironolactone?

Blocks actions of aldosterone; Inhibition of 5a-reductase

Clinical uses: Hypertension or CHF w/other diuretics

What are the toxicities associated with Spironolactone?

•Hyperkalemia

•Hyperchloremic metabolic acidosis

•Gynecomastia

•Impotence

•Benign prostatic hyperplasia

What is Eplerenone used for?

Hypertension, alone or in combination with other medications; full therapeutic effect should be observed within 4 weeks

What is a common adverse reaction of Eplerenone?

•Hyperkalemia

•Hypertriglyceridemia

What is the duration of action for loop diuretics dependent on?

Renal function.

What is the effect of thiazides on calcium reabsorption?

Enhance Ca2+ reabsorption in the kidney

What is a contraindication for thiazide diuretics?

Sulfa allergies

What is the clinical use of Triamterene?

Edema associated with CHF, hepatic cirrhosis, nephrotic syndrome

Does not have efficacy in lowering BP when used alone

What is the mechanism of action of thiazide-like diuretics?

They inhibit NaCl reabsorption

Potassium-Sparing Diuretics

spironolactone, triamterene, amiloride

What are the clinical uses of Amiloride?

- Adjunctive treatment with thiazide or loop diuretic in CHF or hypertension

- has some efficacy in reducing BP

What are the toxicities of amiloride and triamterene?

Hyperkalemia, hyperchloremic metabolic acidosis

What are the contraindications for spironolactone?

•K+ supplements, ACE inhibitors

•Chronic renal insufficiency

What is the action for eplerenone?

Selective antagonism of mineralocorticoid receptor in kidney, heart, blood vessels, and brain

CIs for Eplerenone

•K+ supplements, K+-sparing diuretics, ACE inhibitors

•Chronic renal insufficiency

•Diabetes associated with microalbuminuria

•CYP450 3A4 inhibitors (e.g., ketoconazole)

Diuretics That Act in the Proximal Tubule

carbonic anhydrase inhibitors