heart failure drug, dr anggel

Drug used in Heart Failure

Drug used in Heart Failure

Anggelia Puspasari, MDPharmacology and Therapeutic Dept.Medical Faculty University of Jambi

DefinitionHeart (or cardiac) failure is the pathophysiological state in which the heart is unable to pump blood at a rate commensurate with the requirements of the metabolizing tissues or can do so only from an elevated filling pressure. usually, but not always, caused by a defect in myocardial contractionBraunwald: Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed., Copyright 2001 W. B. Saunders Company

Patophysiology (neurohumoral response)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1128747/

Patophysiology (RAA SYSTEM EFFECT)


Patophysiology ( sympathetic effect)


Sign and Symptom (Farmingham Study)Major CriteriaParoxysmal nocturnal dyspneaNeck vein distentionRalesRadiographic cardiomegalyAcute pulmonary edemaS3 gallopCentral venous pressure>16 cm H2 OHepatojugular refluxPulmonary edema, visceral congestion, or cardiomegaly at autopsyWeight loss 4.5 kg in 5 days in response to treatment of congestive heart failureFrom Ho KL, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: The Framingham Study. J Am Coll Cardiol 22(Suppl A):6A, 1993.

Sign and Symptom (Farmingham Study)Minor CriteriaBilateral ankle edemaNocturnal coughDyspnea on ordinary exertionHepatomegalyPleural effusionDecrease in vital capacity by one third from maximal value recordedTachycardia (rate 120 beats/min)

The diagnosis of congestive heart failure in this study required that two major or one major and two minor criteria be present concurrently. Minor criteria were acceptable only if they could not be attributed to another medical condition.

From Ho KL, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: The Framingham Study. J Am Coll Cardiol 22(Suppl A):6A, 1993.

Goal TreatmentDecompensated HF the goals are to stabilize the patient clinically, restore organ perfusion, return filling pressure to optimal levels, and begin the conversion to chronic therapy. Chronic stable HF the goal are to enhance survival and minimize symptoms.diuretics, vasodilators, and positive inotropic agents are used for both purposes, while neurohormonal/cytokine inhibitors are primarily used to enhance survival.

Braunwald: Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed., Copyright 2001 W. B. Saunders Company

PharmacotherapyDiureticsCarbonic anhydrase inhibitors (acetazolamide)Na+, K+, 2Cl-- cotransporter inhibitors ("loop" diuretics)Na+/Cl-- cotransporter inhibitors (thiazides)Epithelial Na+ channel inhibitors (triamterene, amiloride)Type I (mineralocorticoid/glucocorticoid) receptor antagonists (spironolactone)Vasopressin V2 receptor antagonistsNatriuretic peptides


DiureticSlowed progression of ventricular remodelling by reducing ventricullar filling pressure.Controlling congestive symptom and improving exercise capacity.Except aldosteron antagonist, doesnt reduced mortality.

GOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS - 11th Ed. (2006) Bertram G Katzung, Basic Clinical Pharmacology (9th Ed)

"loop" diuretics

Loop diuretics inhibit a specific ion transport protein, the Na+-K+-2Cl- symporter on the apical membrane of renal epithelial cells in the ascending limb of the loop of Henle .Furosemide, bumetanide, torsemide, and ethacrynic acid.Bioavailability furosemid 40-70%, bumetanide and torsemid 80%Furosemid and bumetanide short actingFurosemid DHF.loading dose 40 mg.maintanance dose 10 mg/hr


Aldosterone antagonistWeak diureticReducing mortality in moderate to severe HFIn HF patient, increasing aldosterone (20x)Spironolactone 12,5 mg-25 mg once dailyRALES study showed reduced mortality and hospitalized caused DCHFPrecaution with creatinin serum more than 2,5 mg/dl and ACEI givinghiper K


PharmacotherapyVasodilatorsNitrovasodilators"Directly acting" or unknown mechanism vasodilatorsCalcium channel blockersATP-regulated K+ channel activatorsVasodilator prostaglandinsNatriuretic peptidesNeurohormonal inhibitors


NitrovasodilatorDecreased preload through venodilatationDecreased afterload through arterialdilatationLongterm used in HF hydralazin and Isosorbid dinitratCCB effective arterial dilatation predominant, older generation shown inotropic (-) effect but 2nd generation like amlodipine, nicardipine and felodipine have fewer inotropic (-) effect safe for treating angina due to HF GOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS - 11th Ed. (2006) Bertram G Katzung, Basic Clinical Pharmacology (9th Ed)Braunwald: Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed., Copyright 2001 W. B. Saunders Company

PharmacotherapyPositive Inotropic AgentsDigitalis derivativesBeta-adrenergic receptor agonistsPhosphodiesterase inhibitorsPhosphodiesterase inhibitors with calcium sensitizer actionPure calcium sensitizers


Digitalized derivatedNaKATPase Blockade, prevent Ca effluks.Parasymphatic agonist receptor predominant.atrial >>>>>in toxic level symphatic predominant.Quabain, digoxin and digitoxinWidely distributed, digoxin well absorbed after oral administrationQuabain and digoxin excrete unexchange by kidneyGOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS - 11th Ed. (2006) Bertram G Katzung, Basic Clinical Pharmacology (9th Ed)

Digitalized derivatedEffect all excitable tissue especially smooth muscle and nervous systemAdverse effect: GI tract (anorexia, nausea, vomitting, diarrhoe), nervous system (disorientation, hallucination), rare effect gynaecomastia.Electrolit imbalance + digitalisinduced arrythmiaGOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS - 11th Ed. (2006) Bertram G Katzung, Basic Clinical Pharmacology (9th Ed)

Beta-adrenergic receptor agonists and others inotropic positive drug

Beta 1 selective agonist.dobutamine and dopamine.Dobutamine, increased CO and decreased ventricular filling pressuresome CHF patient needed intermitten infusion especially with low BP, inadequat MAP.Dobutamine have rapid eliminationDrug inhibit PDE like amrinone, inamrinone have positive inotropic effect and vasodilatation effect.limited efficacyGOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS - 11th Ed. (2006) Bertram G Katzung, Basic Clinical Pharmacology (9th Ed)

PharmacotherapyNeurohormonal or Cytokine InhibitorsRenin-angiotensin-aldosterone inhibitorsAntiadrenergic compoundsEndothelin antagonistsNeutral endopeptidase inhibitorsTumor necrosis factor-alpha inhibitorBraunwald: Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed., Copyright 2001 W. B. Saunders Company

Renin-angiotensin-aldosterone inhibitors

ACE inhibitordecreased PVR (arteriole dilatation predominant)so decreased afterload.ACE inhibitorreduced aldosteron secretionso reduced water and salt retention, decreased preloadReduced long term remodelling of the heart and vessel.Initial dose captopril 6,25 mg and lisinopril 5 mgARB have similar but more limited benefitGOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS - 11th Ed. (2006) Bertram G Katzung, Basic Clinical Pharmacology (9th Ed)

RAA system inhibitor

Antiadrenergic compounds

Beta blocker, augmented sympt blockade..reduced HR and remodelling of the heartBisoprolol, carvedilol and metoprololused in stable heart failure patientb receptor antagonists are now recommended for routine use in patients with an ejection fraction

heart failure drug, dr anggel

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