1. CHAPTER © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 25 Diuretics

2. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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 25-2

3. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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. 25-3

4. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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. 25-4

5. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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 25-5

6. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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. 25-6

7. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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) 25-7

8. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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 25-8

9. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 1-9 https://upload.wikimedia.org/wikipedia/common s/7/72/Renal_Diuretics.gif

10. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. Osmotics/Carbonic Anhydrase Inhibitors 25-10

11. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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 25-11

12. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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 25-12

13. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. Thiazide and Thiazide-like Diuretics 25-13

14. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 1-14 http://www.drugs.com/drug-class/thiazide- diuretics.html

15. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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 25-15

16. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 1-16 https://quizlet.com/1905791/organic-acid- diureticsloop-diuretics-flash-cards/

17. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. Organic Acid Diuretics Side effects are similar to thiazide diuretics: –Nausea –Hypotension –Hypokalemia –Hyperuricemia –Hyperglycemia Additional side effects include: –Ototoxicity 25-17

18. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. Potassium-Sparing Diuretics Inhibit potassium secretion in DCT Produce mild diuresis without electrolyte or acid-base disturbances Side effects: –Nausea –Diarrhea –Hyperkalemia –Gynecomastia 25-18

19. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. Organic Acid/Potassium - Sparing Diuretics 25-19

20. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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. 25-20

21. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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. 25-21

22. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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. 25-22

23. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 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. 25-23

24. © 2012 The McGraw-Hill Companies, Inc. All rights reserved. Preferred Treatment ADH Antagonists Euvolemic and hypervolemic hyponatremia Carbonic Anhydrase Inhibitors Glaucoma, edema with alkalosis and mountain sickness Loop Diuretics Pulmonary and peripheral edema, hypertension and acute renal failure Thiazides Hypertension, mild heart failure, and nephrolithiasis Osmotic Diuretics Improve renal failure, reduce intracranial pressure, glaucoma Potassium- sparing Diuretics Hypokalemia due to other diuretics and post MI 25-24