Drugs for Congestive Heart Failure

Ramesha Tahir

Learning Objectives• Heart failure1) Definition2) Causes3) Sign and symptoms4) Compensatory mechanism in heart failure5) Types of heart failure6) Classes of heart failure7) Stages of heart failure and order of therapy8) Classification of heart failure drugs9) Mechanism of action of drug of choice10) Adverse effects

Heart Failure DefinitionHeart failure (HF) is a complex , progressive disorder in which heart unable to pump sufficient blood to meet the needs of body . Causes of heart failure Heart failure is Due to an impaired ability of heart to adequately filled with And/or eject Blood. Underlying Causes of HF include• Arteriosclerotic heart disease• Myocardial infarction• Hypertensive heart disease • Valvular heart disease • Dilated cardiomyopathy• Congenital heart disease

S&S of Heart Failure

• Dyspnea • Fatigue • Edema• Lack of appetite • Nausea• Confusion• Impaired

thinking • Increased heart

rate

Angiotensin II receptor antagonists/Blockers‘s MOA

• Angiotensin receptors are a class of G protein-coupled receptors which are activated by angiotensin II.

• ARBs block the renin-angiotensin-aldosterone system (RAAS) by competitive antagonism of the AT1 receptor, thereby decreasing afterload and preventing LV remodeling.

• Blockage of AT1 receptors directly causes vasodilation, reduces secretion of vasopressin, and reduces production and secretion of aldosterone, among other actions. The combined effect reduces blood pressure.

• The use of ARBs increases survival and decreases hospitalization rates, but these agents are not superior to ACEIs.

• It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, and it does not affect the response to bradykinin

MOA

RECEPTOR TYPE

LOCATION Effects

AT1 Heart,blood vessels, kidney, adrenal cortex, lung and brain

Vasoconstriction, aldosterone synthesis and secretion, increased vasopressin secretion, cardiac hypertrophy, augmentation of peripheral noradrenergic activity, vascular smooth muscle cells proliferation, decreased renal blood flow, renal renin inhibition, sodium and fluid retention, modulation of central sympathetic nervous system activity, cardiac contractility

AT2 Myometrium,adrenal gland, fallopian tube,fetal kidney and intestine.

Inhibition of cell growth, fetal tissue development, and maybe vasodilation and left ventricular hypertrophy

AT3 & AT4 Role in regulation of the CNS extracellular matrix, as well as modulation of oxytocin release(AT4)

Classification of Anti-Cardiac Failure Drugs

ACE Inhibitors

• Captopril• Enalpril• Fosinopril• Lisinopril• Quinapril• Ramipril

Angiotensin Receptor Blockers(ARBs)• LOSARTAN(Prototype Drug)• Candesartan• Telmisartan• Valsartan• Olmesartan• Irbisartan• Azilsartan

Inotropic Agents• Digoxin• Dobutamine• Inamrinone• Milripone• DopamineAldosterone Antagonists• Eplerenone• Spironolactone

Direct Vasodilators• Hydralazine• Isosorbide dinitrate• Isosorbide mononitrate• Sodium Nitroprusside

Diuretics• Loop Diuretics• Bumetanide• Furosemide• Torsemide• Thiazide Diuretics• Hyderochlorothiazide(HCTZ)• Other Diuretics• Metolazone

β Adrenoreceptor Blocker• Selective β1 Blocker• Atenolol• Metoprolol• Non-Selective β Blocker• Carvedilol• Carteolol

Compenosatory physiological response of HF

Categories of Heart Failure• Types of Heart Failure

• Right heart failure compromises pulmonary flow to the lungs.• Left heart failure compromises aortic flow to the body and brain. Mixed

presentations are common; left heart failure often leads to right heart failure in the longer term.

• Whether the abnormality is due to insufficient contraction (systolic dysfunction), or due to insufficient relaxation of the heart (diastolic dysfunction), or to both.

• Whether the problem is primarily increased venous back pressure (preload), or failure to supply adequate arterial perfusion (afterload).

• Whether the abnormality is due to low cardiac output with high systemic vascular resistance or high cardiac output with low vascular resistance (low-output heart failure vs. high-output heart failure).

American College of Cardiology/American Heart Association STAGES vs New York Heart Association Functional Classification

Order of Therapy in stages of HF

Adverse Effects

Renal Insufficiency

Hypotension

Refrences• www.drugs.com• www.Wikipedia.com• Chap # 16