CHAPTER

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25Diuretics

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Clinical Indication

• Diuretics are used to treat anuria, hypertension, and edema.

• There are six classes of diuretics:– Osmotic agents– Carbonic anhydrase inhibitors– Thiazide and thiazide-like compounds– Organic acids– Potassium-sparing diuretics– ADH antagonists

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Renal Function

• The kidneys are responsible for urine production.

• The working units of the kidney are known as nephrons.

• The nephron is composed of several segments.

• Urine is produced through filtration, reabsorption, and secretion.

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Renal Function

• The renal mechanism for water conservation is dependent upon tubular reabsorption of sodium ions.

• The nephrons secrete hydrogen ions, potassium ions, and weak acids and bases to regulate acid-base balance of the body.

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Renal Dysfunction

• Renal disease and cardiovascular dysfunction alter the functioning of the kidney, leading to:– Decreased urine flow– Decreased urine volume (oliguria)– No urine production (anuria)– Uremia– Edema– Hypotension

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Osmotic Diuretics

• Filtered by glomerulus but not reabsorbed by renal tubules, creating osmotic gradient.

• Stimulate urine flow, producing mild diuresis with no electrolyte imbalance.

• Adverse effects include nausea, dizziness, headache, and chills. Mannitol is contraindicated in patients with edema from cardiovascular insufficiency, pulmonary edema, or intracranial bleeding.

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Carbonic Anhydrase Inhibitors

• Increase sodium and water excretion by inhibiting carbonic anhydrase:– No hydrogen ions to exchange for sodium

ions– Decreased sodium reabsorption– Sodium ions and increased water excreted in

urine– Increased loss of potassium in urine– Decreased bicarbonate in blood (acidosis)

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Carbonic Anhydrase Inhibitors

• Used in the treatment of CHF or drug- induced edema

• Reduce pressure with glaucoma

• Useful in the treatment of epilepsy

• Adverse effects: – Drowsiness– Headache– GI distress– Acidosis

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Osmotics/Carbonic Anhydrase Inhibitors

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Thiazide and Thiazide-like Diuretics

• Inhibit sodium transport in the distal portion of the nephron, causing substantial loss of sodium and water

• Produce intense diuresis

• Can eliminate edema of any cause

• Useful in treatment of mild to moderate hypotension

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Thiazide and Thiazide-like Diuretics

• Mobilization of sodium causes potassium excretion as well (hypokalemia).

• Side effects include:– Hyponatremia– Orthostatic hypotension– Hyperglycemia– Muscle spasms or cramps– GI distress– Headache

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Thiazide and Thiazide-like Diuretics

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http://www.drugs.com/drug-class/thiazide-diuretics.html

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Organic Acid Diuretics (loop diuretics)

• Inhibit sodium and chloride ion transport in the loop of Henle

• Tremendous loss of sodium, chloride, and water

• Highly bound to plasma proteins

• Used for treatment of edema in patients who have become thiazide resistant

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Organic Acid Diuretics

• Side effects are similar to thiazide diuretics:– Nausea– Hypotension– Hypokalemia– Hyperuricemia– Hyperglycemia

• Additional side effects include:– Ototoxicity

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Potassium-Sparing Diuretics

• Inhibit potassium secretion in DCT

• Produce mild diuresis without electrolyte or acid-base disturbances

• Side effects:– Nausea– Diarrhea – Hyperkalemia– Gynecomastia

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Organic Acid/Potassium-Sparing Diuretics

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ADH Antagonists

• ADH regulates water balance in the body.

• ADH antagonists block the ADH receptors in the kidneys.

• Inhibition of ADH receptors causes excretion of free water without electrolyte loss.

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Miscellaneous Diuretics

• Xanthine derivatives are naturally occurring drugs that produce mild diuretic responses.

• They stimulate urine flow by increasing blood flow to kidneys.

• Side effects include CNS stimulation, hypotension, and headache.

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Special Considerations

• Most diuretics cause electrolyte and acid-base imbalance:– Potassium loss is most common.– Patients should supplement potassium.

• Blood pressure may be altered.

• Blood glucose levels may be altered.

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Drug Interactions and Incompatibilities

• Diuretics are involved in a number of drug interactions due to their MOA:– Bind to plasma proteins– Alter acid-base balance– Stimulate renal excretion

• Diuretics when mixed in IVs with other solutions can cause precipitate formation.

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Preferred Treatment

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