IVMS-CV Pharmacology -Diuretic Agents

CV Pharmacology Diuretic Agents : CV Pharmacology Diuretic Agents Prepared and Presenter: Marc Imhotep Cray, M.D. Associate Professor Pharmacology Recommended Reading:   Renal Pharmacology IAU Medical Pharmacology and Therapeutics Diuretics Notes/ PDF Formative Assessment Practice question set #1 Clinical: E-Medicine Article Hypokalemia Illustration Hot-Linked to Renal Physio and Pharm/Pharm2000

This illustration shows where some types of diuretics act, and how : 3/6/2010 2 This illustration shows where some types of diuretics act, and how See IAU Medical Pharmacology and Therapeutics Diuretics Notes/ PDF

Diuretic Agents : 3/6/2010 3 Diuretic Agents Drugs that accelerate the rate of urine formation Result: removal of sodium and water

Sodium : 3/6/2010 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

Diuretic Agents : 3/6/2010 5 Diuretic Agents Carbonic anhydrase inhibitors Loop diuretics Osmotic diuretics Potassium-sparing diuretics Thiazide and thiazide-like diuretics

Carbonic Anhydrase Inhibitors : 3/6/2010 6 Carbonic Anhydrase Inhibitors (CAIs) acetazolamide (Diamox) methazolamide 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)

Carbonic Anhydrase Inhibitors: Mechanism of Action : 3/6/2010 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

Carbonic Anhydrase Inhibitors: Mechanism of Action : 3/6/2010 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

Carbonic Anhydrase Inhibitors: Therapeutic Uses : 3/6/2010 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

Carbonic Anhydrase Inhibitors: Therapeutic Uses : 3/6/2010 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

Carbonic Anhydrase Inhibitors: Side Effects : 3/6/2010 11 Carbonic Anhydrase Inhibitors: Side Effects hyperchloremic metabolic acidosis Drowsiness Anorexia Paresthesias Hematuria Urticaria Photosensitivity Melena

Loop Diuretics : 3/6/2010 12 Loop Diuretics bumetanide (Bumex) ethacrynic acid (Edecrin) furosemide (Lasix)

Loop Diuretics: Mechanism of Action : 3/6/2010 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

Loop Diuretics: Drug Effects : 3/6/2010 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

Loop Diuretics: Therapeutic Uses : 3/6/2010 15 Loop Diuretics: Therapeutic Uses Edema associated with CHF or hepatic or renal disease Control of hypertension

Loop Diuretics: Side Effects : 3/6/2010 16 Loop Diuretics: Side Effects Body System Effect CNS Dizziness headache tinnitus blurred vision GI Nausea/vomiting, diarrhea

Loop Diuretics: Side Effects : 3/6/2010 17 Loop Diuretics: Side Effects Body System Effect Hematologic Agranulocytosis, neutropenia, thrombocytopenia Metabolic Hypokalemia, hyperglycemia, hyperuricemia

Osmotic Diuretics : 3/6/2010 18 Osmotic Diuretics mannitol (Resectisol, Osmitrol)

Osmotic Diuretics: Mechanism of Action : 3/6/2010 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

Osmotic Diuretics: Drug Effects : 3/6/2010 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

Osmotic Diuretics: Therapeutic Uses : 3/6/2010 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

Osmotic Diuretics: Side Effects : 3/6/2010 22 Osmotic Diuretics: Side Effects Convulsions Thrombophlebitis Pulmonary congestion Also headaches, chest pains, tachycardia,blurred vision, chills, and fever

Potassium-Sparing Diuretics : 3/6/2010 23 Potassium-Sparing Diuretics amiloride (Midamor) spironolactone (Aldactone) triamterene (Dyrenium)

Potassium-Sparing Diuretics: Mechanism of Action : 3/6/2010 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

Potassium-Sparing Diuretics: Drug Effects : 3/6/2010 25 Potassium-Sparing Diuretics: Drug Effects Prevent potassium from being pumped into the tubule, thus preventing its secretion Competitively block the aldosterone receptors and inhibit its action The excretion of sodium and water is promoted

Potassium-Sparing Diuretics: Therapeutic Uses : 3/6/2010 26 Potassium-Sparing Diuretics: Therapeutic Uses spironolactone and triamterene Hyperaldosteronism Hypertension Reversing the potassium loss caused by potassium-losing drugs amiloride Treatment of CHF

Potassium-Sparing Diuretics: Side Effects : 3/6/2010 27 Potassium-Sparing Diuretics: Side Effects Body System Effect CNS Dizziness, headache GI Cramps, nausea, vomiting, diarrhea Other Urinary frequency, weakness **hyperkalemia

Potassium-Sparing Diuretics: Side Effects : 3/6/2010 28 Potassium-Sparing Diuretics: Side Effects spironolactone gynecomastia, amenorrhea, irregular menses

Thiazide and Thiazide-Like Diuretics : 3/6/2010 29 Thiazide and Thiazide-Like Diuretics hydrochlorothiazide (Esidrix, HydroDIURIL) chlorothiazide (Diuril) trichlormethiazide (Metahydrin) chlorthalidone (Hygroton) metolazone (Mykrox, Zaroxolyn)

Thiazide and Thiazide-Like Diuretics: Mechanism of Action : 3/6/2010 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

Thiazide and Thiazide-Like Diuretics: Drug Effects : 3/6/2010 31 Thiazide and Thiazide-Like Diuretics: Drug Effects Lowered peripheral vascular resistance Depletion of sodium and water

Thiazide and Thiazide-Like Diuretics: Therapeutic Uses : 3/6/2010 32 Thiazide and Thiazide-Like Diuretics: Therapeutic Uses Hypertension (one of the most prescribed group of agents) Edematous states Idiopathic hypercalciuria Diabetes insipidus Adjunct agents in treatment of CHF, hepatic cirrhosis

Thiazide and Thiazide-Like Diuretics: Side Effects : 3/6/2010 33 Thiazide and Thiazide-Like Diuretics: Side Effects Body System Effect CNS Dizziness, headache, blurred vision, paresthesias, decreased libido GI Anorexia, nausea, vomiting, diarrhea

Thiazide and Thiazide-Like Diuretics: Side Effects : 3/6/2010 34 Thiazide and Thiazide-Like Diuretics: Side Effects Body System Effect GU Impotence Integumentary Urticaria, photosensitivity Metabolic Hypokalemia, glycosuria, hyperglycemia

Reference Resources : 3/6/2010 35 Reference Resources Drug Monitor - Diuretics Diagram at cvpharmacology.com Renal Physiology And Disease