CV Pharmacology Diuretic Agents Illustration Hot-Linked to Renal Physio and Pharm/Pharm2000
Reading/eNotes: Renal Pharmacology Clinical: e-Medicine article Hypokalemia
Prepared and presented by Marc Imhotep Cray, M.D. Basic Medical Sciences & CK Teacher
Illustration shows where some types of diuretics act, and how
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Diuretic Agents ď Ž
ď Ž
Drugs that accelerate the rate of urine formation Result: removal of sodium and water
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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 4
Diuretic Agents 1. 2. 3. 4. 5.
Carbonic anhydrase inhibitors Loop diuretics Osmotic diuretics Potassium-sparing diuretics Thiazide and thiazide-like diuretics
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Carbonic Anhydrase Inhibitors (CAIs) 1. acetazolamide (Diamox) 2. methazolamide 3. Dichlorphenamide ď Ž MOA: these agents block formation of H+ and HCO3- from CO2 and H2O. ď Ž The end result is that bicarbonate is excreted in the urine. (see notes page for more) 6
Carbonic Anhydrase Inhibitors: Mechanism of Action ď Ž
ď Ž
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
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Carbonic Anhydrase Inhibitors: Mechanism of Action
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
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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
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Carbonic Anhydrase Inhibitors: Therapeutic Uses ď Ž
ď Ž
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
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Carbonic Anhydrase Inhibitors: Side Effects hyperchloremic metabolic acidosis Drowsiness Anorexia Paresthesias Hematuria Urticaria Photosensitivity Melena 11
Loop Diuretics
bumetanide (Bumex) ethacrynic acid (Edecrin) furosemide (Lasix)
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Loop Diuretics: Mechanism of Action ď Ž
ď Ž
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
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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 14
Loop Diuretics: Therapeutic Uses ď Ž
ď Ž
Edema associated with CHF or hepatic or renal disease Control of hypertension
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Loop Diuretics: Side Effects Body System CNS
Effect Dizziness headache tinnitus blurred vision
GI Nausea/vomiting, diarrhea 16
Loop Diuretics: Side Effects Body System Hematologic
Metabolic
Effect Agranulocytosis, neutropenia, thrombocytopenia Hypokalemia, hyperglycemia, hyperuricemia 17
Osmotic Diuretics ď Ž
mannitol (Resectisol, Osmitrol)
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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
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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 20
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
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Osmotic Diuretics: Side Effects
Convulsions Thrombophlebitis Pulmonary congestion Also headaches, chest pains, tachycardia, blurred vision, chills, and fever
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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 23
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 24
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 25
Potassium-Sparing Diuretics: Therapeutic Uses spironolactone and triamterene
Hyperaldosteronism
Hypertension
Reversing potassium loss caused by potassium-losing drugs
amiloride
Treatment of CHF 26
Potassium-Sparing Diuretics: Side Effects Body System
Effect
CNS
Dizziness, headache
GI Other
Cramps, nausea, vomiting, diarrhea Urinary frequency, weakness **hyperkalemia 27
Potassium-Sparing Diuretics: Side Effects spironolactone ď Ž
gynecomastia, amenorrhea, irregular menses
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Thiazide and Thiazide-Like Diuretics
hydrochlorothiazide (Esidrix, HydroDIURIL)
chlorothiazide (Diuril)
trichlormethiazide (Metahydrin)
chlorthalidone (Hygroton)
metolazone (Mykrox, Zaroxolyn) 29
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
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Thiazide and Thiazide-Like Diuretics: Drug Effects ď Ž ď Ž
Lowered peripheral vascular resistance Depletion of sodium and water
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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 32
Thiazide and Thiazide-Like Diuretics: Side Effects Body System
Effect
CNS
Dizziness, headache, blurred vision, paresthesias, decreased libido Anorexia, nausea, vomiting, diarrhea
GI
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Thiazide and Thiazide-Like Diuretics: Side Effects Body System
Effect
GU Integumentary Metabolic
Impotence Urticaria, photosensitivity Hypokalemia, glycosuria, hyperglycemia
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Additional Resources
Drug Monitor - Diuretics Diagram at cvpharmacology.com Renal Physiology And Disease
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