IVMS-CV Pharmacology -Diuretic Agents

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Individualized Webcam facilitated and e-Classroom USMLE Step 1 Tutorials with Dr. Cray. 1 BMS Unit is 4 hr. General Principles and some Organ System require multiple units to complete in preparation for the USMLE Step 1 A HIGH YIELD FOCUS IN Biochemistry / Cell Biology, Microbiology / Immunology and the 4 P’s-Phiso, Pathophys, Path and Pharm. Webcam Facilitated USMLE Step 2 Clinical Knowledge and Clinical Skills diadactic tutorials /1 Unit is 4 hours, individualized one-on-one and group sessions, Including all Internal Medicine sub-sub-specitialities. For questions or more information.. drcray@imhotepvirtualmedsch.com

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IVMS-CV Pharmacology -Diuretic Agents

  1. 1. CV Pharmacology Diuretic Agents Reading/eNotes: Renal Pharmacology Clinical: e-Medicine article Hypokalemia IllustrationHot-LinkedtoRenalPhysioandPharm/Pharm2000 Prepared and presented by Marc Imhotep Cray, M.D. Basic Medical Sciences & CK Teacher
  2. 2. 2 Illustration shows where some types of diuretics act, and how
  3. 3. 3 Diuretic Agents  Drugs that accelerate the rate of urine formation  Result: removal of sodium and water
  4. 4. 4 Sodium As goes sodium so goes water  20 to 25% of all sodium is reabsorbed into the bloodstream in the loop of Henle  5 to 10% in the distal tubules,  3% in collecting ducts  If not absorbed, it is excreted with the urine
  5. 5. 5 Diuretic Agents 1. Carbonic anhydrase inhibitors 2. Loop diuretics 3. Osmotic diuretics 4. Potassium-sparing diuretics 5. Thiazide and thiazide-like diuretics
  6. 6. 6 Carbonic Anhydrase Inhibitors (CAIs) 1. acetazolamide (Diamox) 2. methazolamide 3. Dichlorphenamide  MOA: these agents block formation of H+ and HCO3- from CO2 and H2O.  The end result is that bicarbonate is excreted in the urine. (see notes page for more)
  7. 7. 7 Carbonic Anhydrase Inhibitors: Mechanism of Action  The enzyme carbonic anhydrase helps to make H+ ions available for exchange with sodium and water in the proximal tubules  CAIs block the action of carbonic anhydrase, thus preventing the exchange of H+ ions with sodium and water
  8. 8. 8  Inhibition of carbonic anhydrase reduces H+ ion concentration in renal tubules  As a result, there is increased excretion of bicarbonate, sodium, water, and potassium  Reabsorption of water is decreased and urine volume is increased Carbonic Anhydrase Inhibitors: Mechanism of Action
  9. 9. 9 Carbonic Anhydrase Inhibitors: Therapeutic Uses  Adjunct agents in the long-term management of open-angle glaucoma  Used with miotics to lower intraocular pressure before ocular surgery in certain cases  Also useful in the treatment of:  Glaucoma  Edema  Epilepsy  High-altitude sickness
  10. 10. 10  Acetazolamide is used in the management of edema secondary to CHF when other diuretics are not effective  CAIs are less potent diuretics than loop diuretics or thiazides—metabolic acidosis they induce reduces their diuretic effect in 2 to 4 days Carbonic Anhydrase Inhibitors: Therapeutic Uses
  11. 11. 11 Carbonic Anhydrase Inhibitors: Side Effects hyperchloremic metabolic acidosis Drowsiness Anorexia Paresthesias Hematuria Urticaria Photosensitivity Melena
  12. 12. 12 Loop Diuretics  bumetanide (Bumex)  ethacrynic acid (Edecrin)  furosemide (Lasix)
  13. 13. 13 Loop Diuretics: Mechanism of Action  Act directly on the ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption  Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance
  14. 14. 14 Loop Diuretics: Drug Effects  Potent diuresis and subsequent loss of fluid  Decreased fluid volume causes:  Reduced BP  Reduced pulmonary vascular resistance  Reduced systemic vascular resistance  Reduced central venous pressure  Reduced left ventricular end-diastolic pressure  Potassium depletion
  15. 15. 15 Loop Diuretics: Therapeutic Uses  Edema associated with CHF or hepatic or renal disease  Control of hypertension
  16. 16. 16 Loop Diuretics: Side Effects Body System Effect CNS Dizziness headache tinnitus blurred vision GI Nausea/vomiting, diarrhea
  17. 17. 17 Loop Diuretics: Side Effects Body System Effect Hematologic Agranulocytosis, neutropenia, thrombocytopenia Metabolic Hypokalemia, hyperglycemia, hyperuricemia
  18. 18. 18 Osmotic Diuretics  mannitol (Resectisol, Osmitrol)
  19. 19. 19 Osmotic Diuretics: Mechanism of Action  Work in the proximal tubule  Nonabsorbable, producing an osmotic effect  Pull water into the blood vessels and nephrons from the surrounding tissues
  20. 20. 20 Osmotic Diuretics: Drug Effects  Reduced cellular edema  Increased urine production, causing diuresis  Rapid excretion of water, sodium, and other electrolytes, as well as excretion of toxic substances from the kidney  Reduces excessive intraocular pressure
  21. 21. 21 Osmotic Diuretics: Therapeutic Uses  Used in the treatment of patients in the early, oliguric phase of ARF  To promote the excretion of toxic substances  Reduction of intracranial pressure  Treatment of cerebral edema
  22. 22. 22 Osmotic Diuretics: Side Effects  Convulsions  Thrombophlebitis  Pulmonary congestion Also headaches, chest pains, tachycardia, blurred vision, chills, and fever
  23. 23. 23 Potassium-Sparing Diuretics  Do not share any obvious chemical similarities, except for steroid-structure, of the aldosterone antagonists  Those in clinical use include:  Epithelial sodium channel blockers:  Amiloride  Triamterene  Aldosterone antagonists:  Spironolactone  Eplerenone
  24. 24. 24 Potassium-Sparing Diuretics: Mechanism of Action  Work in collecting ducts and distal convoluted tubules  Interfere with sodium-potassium exchange  Competitively bind to aldosterone receptors  Block the reabsorption of sodium and water usually induced by aldosterone
  25. 25. 25 Potassium-Sparing Diuretics: Drug Effects  Prevent potassium from being pumped into tubule, thus preventing its secretion  Competitively block aldosterone receptors and inhibit its action  Excretion of sodium and water is promoted
  26. 26. 26 Potassium-Sparing Diuretics: Therapeutic Uses spironolactone and triamterene  Hyperaldosteronism  Hypertension  Reversing potassium loss caused by potassium-losing drugs amiloride  Treatment of CHF
  27. 27. 27 Potassium-Sparing Diuretics: Side Effects Body System Effect CNS Dizziness, headache GI Cramps, nausea, vomiting, diarrhea Other Urinary frequency, weakness **hyperkalemia
  28. 28. 28 Potassium-Sparing Diuretics: Side Effects spironolactone  gynecomastia, amenorrhea, irregular menses
  29. 29. 29 Thiazide and Thiazide-Like Diuretics  hydrochlorothiazide (Esidrix, HydroDIURIL)  chlorothiazide (Diuril)  trichlormethiazide (Metahydrin)  chlorthalidone (Hygroton)  metolazone (Mykrox, Zaroxolyn)
  30. 30. 30 Thiazide and Thiazide-Like Diuretics: Mechanism of Action  Inhibit tubular resorption of sodium and chloride ions  Action primarily in the ascending loop of Henle and early distal tubule  Result: water, sodium, and chloride are excreted  Potassium is also excreted to a lesser extent  Dilate the arterioles by direct relaxation
  31. 31. 31 Thiazide and Thiazide-Like Diuretics: Drug Effects  Lowered peripheral vascular resistance  Depletion of sodium and water
  32. 32. 32 Thiazide and Thiazide-Like Diuretics: Therapeutic Uses  Hypertension (one of most prescribed group of agents)  Edematous states  Idiopathic hypercalciuria  Diabetes insipidus  Adjunct agents in treatment of CHF, hepatic cirrhosis
  33. 33. 33 Thiazide and Thiazide-Like Diuretics: Side Effects Body System Effect CNS Dizziness, headache, blurred vision, paresthesias, decreased libido GI Anorexia, nausea, vomiting, diarrhea
  34. 34. 34 Thiazide and Thiazide-Like Diuretics: Side Effects Body System Effect GU Impotence Integumentary Urticaria, photosensitivity Metabolic Hypokalemia, glycosuria, hyperglycemia
  35. 35. 35 Additional Resources  Drug Monitor - Diuretics  Diagram at cvpharmacology.com  Renal Physiology And Disease

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