IVMS-CV Pharmacology -Diuretic Agents

CV PharmacologyDiuretic AgentsPrepared and Presenter: Marc Imhotep Cray, M.D.Associate Professor PharmacologyRecommended Reading:Renal PharmacologyIAU Medical Pharmacology and TherapeuticsDiuretics Notes/PDFFormative AssessmentPractice question set #1Clinical:E-Medicine ArticleHypokalemiaIllustration Hot-Linked to Renal Physio and Pharm/Pharm20009/29/20092This illustration shows where some types of diuretics act, and howSee IAU Medical Pharmacology and TherapeuticsDiuretics Notes/PDF9/29/20093Diuretic AgentsDrugs that accelerate the rate of urine formationResult: removal of sodium and water9/29/20094SodiumAs 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 urine9/29/20095Diuretic Agents1.Carbonic anhydrase inhibitors2.Loop diuretics3.Osmotic diuretics4.Potassium-sparing diuretics5.Thiazide and thiazide-like diuretics9/29/20096Carbonic Anhydrase Inhibitors(CAIs)1.acetazolamide (Diamox)2.methazolamide3.DichlorphenamideMOA:these agents block formation of H+ and HCO3-from CO2 and H2O. The end result is that bicarbonateis excreted in the urine. (see notes page for more)9/29/20097Carbonic 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 water9/29/20098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 increasedCarbonic Anhydrase Inhibitors: Mechanism of Action9/29/20099Carbonic 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 sickness9/29/200910Acetazolamide is used in the management of edema secondary to CHF when other diuretics are not effectiveCAIsare less potent diuretics than loop diuretics or thiazides—metabolic acidosis they inducereduces their diuretic effect in 2 to 4 daysCarbonic Anhydrase Inhibitors: Therapeutic Uses9/29/200911Carbonic Anhydrase Inhibitors: Side Effectshyperchloremic metabolic acidosisDrowsinessAnorexiaParesthesiasHematuriaUrticariaPhotosensitivityMelena9/29/200912Loop Diureticsbumetanide (Bumex)ethacrynic acid (Edecrin)furosemide (Lasix)9/29/200913Loop 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 vesselsand reduced peripheral vascular resistance9/29/200914Loop 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 depletion9/29/200915Loop Diuretics: Therapeutic UsesEdema associated with CHF or hepatic or renal diseaseControl of hypertension9/29/200916Loop Diuretics: Side EffectsBody System EffectCNSDizzinessheadache tinnitusblurred visionGINausea/vomiting, diarrhea9/29/200917Loop Diuretics: Side EffectsBody System EffectHematologicAgranulocytosis, neutropenia, thrombocytopeniaMetabolicHypokalemia, hyperglycemia,hyperuricemia9/29/200918Osmotic Diureticsmannitol (Resectisol, Osmitrol)9/29/200919Osmotic 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 tissues9/29/200920Osmotic 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 pressure9/29/200921Osmotic 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 edema9/29/200922Osmotic Diuretics: Side EffectsConvulsionsThrombophlebitisPulmonary congestionAlso headaches, chest pains, tachycardia,blurred vision, chills, and fever9/29/200923Potassium-Sparing Diureticsamiloride (Midamor)spironolactone (Aldactone)triamterene (Dyrenium)9/29/200924Potassium-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 aldosterone9/29/200925Potassium-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 promoted9/29/200926Potassium-Sparing Diuretics: Therapeutic Usesspironolactone and triamtereneHyperaldosteronismHypertensionReversing the potassium loss caused by potassium-losing drugsamilorideTreatment of CHF9/29/200927Potassium-Sparing Diuretics: Side EffectsBody System EffectCNSDizziness, headacheGICramps, nausea, vomiting, diarrheaOtherUrinary frequency,weakness**hyperkalemia9/29/200928Potassium-Sparing Diuretics: Side Effectsspironolactonegynecomastia, amenorrhea, irregular menses9/29/200929Thiazide and Thiazide-Like Diureticshydrochlorothiazide (Esidrix, HydroDIURIL)chlorothiazide (Diuril)trichlormethiazide (Metahydrin)chlorthalidone (Hygroton)metolazone (Mykrox, Zaroxolyn)9/29/200930Thiazide 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 relaxation9/29/200931Thiazide and Thiazide-Like Diuretics: Drug EffectsLowered peripheral vascular resistanceDepletion of sodium and water9/29/200932Thiazide 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 cirrhosis9/29/200933Thiazide and Thiazide-Like Diuretics: Side EffectsBody SystemEffectCNSDizziness, headache, blurred vision, paresthesias,decreased libidoGIAnorexia, nausea, vomiting,diarrhea9/29/200934Thiazide and Thiazide-Like Diuretics: Side EffectsBody SystemEffectGUImpotenceIntegumentaryUrticaria, photosensitivityMetabolicHypokalemia, glycosuria,hyperglycemia 9/29/200935Reference ResourcesDrug Monitor -DiureticsDiagram at cvpharmacology.comRenal Physiology And Disease