Acvp ivms cv pharmacology diuretic agents

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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