CVS_HF I PDF

 Heart failure (HF)I Objectives:- By the end of lec. 1 and 2 the student will be able to classify groups of drugs used in heart failure with their detailed mechanism of action, indications and adverse effect. Heart failure (HF) is a complex, progressive...

 Heart failure (HF)I Objectives:- By the end of lec. 1 and 2 the student will be able to classify groups of drugs used in heart failure with their detailed mechanism of action, indications and adverse effect. Heart failure (HF) is a complex, progressive disorder in which the heart is unable to pump sufficient blood to meet the needs of the body. Its serious symptoms are dyspnea, fatigue, and fluid retention. It is often accompanied by abnormal increases in blood volume and interstitial fluid (hence the term “congestive” HF, because symptoms include dyspnea from pulmonary congestion in left HF and peripheral edema in right HF). Two major types of Hf may be distinguished. Approximately 50% of younger patients have systolic failure with reduced mechanical pumping (contractility) and reduced ejection fraction (HFrEf), the remaining group have diastolic failure with stiffening and loss of adequate relaxation playing a major role in reducing filling and cardiac output. Underlying causes of HF include 1) arteriosclerotic heart disease 2) myocardial infarction 3) hypertensive heart disease 4) valvular heart disease 5) dilated cardiomyopathy 6) congenital heart disease. Goals of pharmacologic intervention in HF The goals are to: -  Alleviate symptoms.  Slow disease progression,  In addition, improve survival. 1  Accordingly, ten classes of drugs have been shown to be effective: 1) angiotensin-converting enzyme (ACE) inhibitors. 2) angiotensin receptor blockers. 3) aldosterone antagonists. 4) β-blockers. 5) diuretics. 6) direct vaso- and venodilators. 7) hyperpolarization-activated cyclic nucleotide-gated channel blockers. 8) inotropic agents. 9) the combination of a neprilysin inhibitor with an angiotensin receptor blocker. 10) recombinant B-type natriuretic peptide Compensatory physiological responses in HF The failing heart evokes four major compensatory mechanisms to enhance cardiac output.  Increased sympathetic activity: Baroreceptors sense a decrease in blood pressure and activate the sympathetic nervous system, which stimulates B-adrenergic receptors in the heart. This results in an increased heart rate and a greater force of contraction of the heart muscle. In addition, vasoconstriction enhances venous return and increases cardiac preload. These compensatory responses increase the work of the heart and, therefore, can contribute to further decline in cardiac function.  Activation of the renin-angiotensin system: A fall in cardiac output decreases blood flow to the kidney, stimulating the release of renin, with a resulting increase in the formation of angiotensin II and release of aldosterone. This results in increased peripheral resistance and retention of sodium and water. Blood volume increases, and more blood is returned to the heart. If the heart is unable to pump this extra volume, venous pressure increases and peripheral edema and pulmonary edema occur. These compensatory responses increase the work of the heart and, therefore, can contribute to further decline in cardiac function. 2  Activation of natriuretic peptides:- An increase in preload also increases the release of natriuretic peptides. Natriuretic peptides, which include atrial, B-type, and C-type, have differing roles in HF; atrial and B-type natriuretic peptides are the most important. Activation of the natriuretic peptides ultimately results in vasodilation, natriuresis, inhibition of renin and aldosterone release, and a reduction in myocardial fibrosis. This beneficial response may improve cardiac function and HF symptoms.  Myocardial hypertrophy: The heart increases in size, and the chambers dilate and become more globular. Initially, stretching of the heart muscle leads to a stronger contraction of the heart. Acute (Decompensated) HF If the mechanisms listed above adequately restore cardiac output, the HF is said to be compensated. These compensations increase the work of the heart and contribute to further decline in cardiac performance. If the adaptive mechanisms fail to maintain cardiac output, the HF is termed decompensated. Therapeutic strategies in HF Chronic HF is typically managed by:  Reduction in physical activity  Low dietary intake of sodium (