Chapter 46 - Drugs For Heart Failure

CHAPTER 46

DRUGS

FOR

HEART FAILURE

Heart failure (HF) is a serious, progressive disorder characterized by ventricular dysfunction, reduced cardiac output, insufficient tissue perfusion, and signs of fluid retention. - commonly referred to as congestive heart failure - causes fluid accumulation (congestion) in the lungs and peripheral tissues - principal drugs employed for treatment are angiotensin-converting enzyme (ACE) inhibitors, diuretics, beta blockers, and digoxin

I.

PATHOPHYSIOLOGY

OF

HEART FAILURE

- syndrome is characterized by signs of inadequate tissue perfusion (fatigue, shortness of breath, exercise intolerance) and/or signs of volume overload - major underlying causes of HF are chronic hypertension and myocardial infarction - other causes include valvular disease, coronary artery disease, congenital heart disease, dysrhthmias, and aging of the myocardium - HF is a chronic disorder that requires continuous treatment with drugs A.

SIGNS

SYMPTOMS - decreased tissue perfusion results in reduced exercise tolerance, fatigue, and shortness of breath - shortness of breath may also stem from pulmonary edema - increased sympathetic tone produces tachycardia - increased ventricular filling, reduced systolic ejection, and myocardial hypertrophy result in cardiomegaly (increased heart size) - combination of increased venous tone plus increased blood volume helps cause pulmonary edema, peripheral edema, hepatomegaly (increased liver size) and distention of the jugular veins - weight gain results from fluid retention

II.

OVERVIEW

A.

ACE INHIBITORS

B.

ARBS

C.

AND

OF

DRUGS

USED TO

AND OTHER

TREAT HEART FAILURE

VASODILATORS

DIURETICS - first line drugs for all patients with signs of volume overload (or with a history of volume overload)

- by reducing blood volume, can decrease venous pressure, arterial pressure (afterload), pulmonary edema, peripheral edema, and cardiac dilation - excessive diuretics is hazardous and must be avoided 1.

Thiazide Diuretics – hydrochorothiazide - produce moderate diuresis - oral agents used for long-term therapy of HR when edema is

not too great - cannot be used if cardiac output is greatly reduced -principal adverse effect is hypokalemia which increases the risk of digoxin-induced dysrhythmias 2.

High-Ceiling (Loop) Diuretics – furosemide - produce profound diuresis - can promote fluid loss even when GFR is low - preferred to thiazides when cardiac output is greatly reduced - administration may be oral or IV - drug of choice for patients with severe HF - can cause hypokalemia, increasing the risk of digoxin toxicity - can cause severe hypotension secondary to excessive

volume reduction 3.

Potassium-Sparing Diuretics – spironolactone, triamterene - promote only scant diuresis - employed to counteract potassium loss caused by thiazide and loop diuretics, lowering the risk of digoxin-induced dysrhythmias - principal adverse effect is hyperkalemia - caution is need if combined with ACE inhibitors - spironlactone prolongs survival in patients with HF primarily by blocking receptors for aldosterone, not by causing diuresis D.

BETA BLOCKERS - names end in “ol” - carvedilol, metoprolol, and bisoprolol - when added to conventional therapy can improve left ventricular (LV) ejection fraction, increase exercise tolerance, slow progression of HF, reduce the need for hospitalization, and, most importantly, prolong survival - mechanism underlying benefits possibly include protecting the heart from excessive sympathetic stimulation and protecting against dysrhythmias - full benefits may not be seen for 1 – 3 months

- principal adverse effects are: fluid retention and worsening of HF fatigue hypotension bradycardia or heart block - carvedilol (Coreg) and metoprolol (Lopressor, Toprol XL) are the only beta blockers approved E.

INOTROPIC AGENTS - drugs that increase the force of myocardial contraction - given to improve performance of the failing heart - type available: cardiac glycosides, sympathomimetics, and phophodiesterase (PDE) inhibitors - sympathomimetics and PDE inhibitors currently available must be administered by IV infusion - use is generally restricted to acute care of hospitalized patients 1.

Cardiac Glycosides – digoxin - used widely for long-term therapy - do not prolong life - cardiac glycosides are the only intropic agents that can be taken orally, therefore, suited for long-term therapy 2.

Sympathomimetic Drugs: Dopamine and Dobutamine a. Dopamine – intropin - can activate: beta1-adrenergic receptors in the heart – increases heart rate, creating a risk of tachycardia dopamine receptors in the kidney – dilates renal blood vessels, increasing renal blood flow and urine output at high doses, alpha1-adrenergic receptors in blood vessels – increases vascular resistance (afterload), reducing cardiac output - administered by continuous infusion - constant monitoring of BP, electrocardiogram (EKG) and urine output is required - employed as a short-term rescue measure for severe, acute cardiac failure b. receptors

Dobutamine – dobutrex - causes selective activation of beta1-adrenergic

- can increase myocardial contractility, improving cardiac performance - can cause tachycardia - does not activate alpha1 receptors, therefore, does not increase vascular resistance - generally preferred to dopamine for short-term treatment of acute HF - administered by continuous infusion e.

Phosphodiesterase (PDE) Inhibitors Inamrinone – inocor - called an inodilator because it increases myocardial contractility and promotes vasodilation - increased contractility results from intracellular accumulation of cyclic AMP secondary to inhibition of PDE-3 (enzyme that normally degrades cAMP) - improvements in cardiac function elicited by amrinone are superior to those elicited by dopamine or dobutamine - administered by IV infusion - not suited for outpatient use - only for short-term treatment - should be protected from light and should not be mixed with glucose containing solutions F.

SPIRONOLACTONE: ALDOSTERONE RECEPTOR BLOCKER - aldactone - can reduce symptoms, decrease hospitalization, and prolong life in moderate to severe HF - helps HF by blocking receptors for aldosterone - benefits in HF do not result primarily from diuresis and potassium retention, instead they result from blockade of receptors for aldosterone, primarily in the heart and blood vessels Aldosterone’s Harmful Effects: • promotion of myocardial remodeling (which impairs pumping) • promotion of myocardial fibrosis (which increases the risk of dysrhythmias) • activation of the sympathetic nervous system and suppression of norepinephrine uptake in the heart (both of which can promote dysrhythmias and ischemia) • promotion of vascular fibrosis (which decreases arterial compliance)

• promotion of baroreceptors dysfunction - spironolactone blocks aldosterone actions - when added to regimen, residual effects are nearly eliminated - adverse effects gynecomastia – breast enlargement, which develops in men - is cosmetically troublesome and painful - is caused by blocking receptors for testosterone hyperkalemia – caused by decreasing renal excretion of potassium - potassium levels should be monitored

III.

CARDIAC (DIGITALIS) GLYCOSIDES

- naturally occurring compounds (and one of the most dangerous) that have profound effects on the mechanical and electrical properties of the heart - by improving mechanical function of the heart, can reduce symptoms of HF - by altering electrical properties of the heart, can suppress dysrhythmias – or cause them - toxicity results from the drug’s propensity to cause dysrhythmias - these drugs are used with respect, caution and skill A.

DIGOXIN - lanoxin, lanoxicaps, digitek are indicated for HF and dysrhythmias - patient telemetry must be monitored - for HF, can reduce symptoms, increase exercise tolerance, and decease hospitalization - does not prolong life - when used by women, it may actually shorten the life span 1.

Digoxin’s Mechanical Effects on the Heart - exerts a positive inotropic action - - increases the force of ventricular contraction, increasing cardiac output 2. Digoxin’s Adminstration – therapeutic range is 0.5 – 1.1 ng/ml (levels above 2.0 ng/ml are toxic) - can be administered orally and intravenously - intramuscular administration causes severe pain and tissue damage – should be avoided - prior to administration, the rate and regularity of the heart beat should be determined - if heart rate is less than 60 beats/min or if a change in rhythm is detected – DO NOT ADMINISTER and call the physician - cardiac status should be monitored continuously for 1 – 2 hours

IV.

MANAGEMENT

OF

HEART FAILURE

A.

STAGE A - no symptoms of HF - no structural or functional cardiac abnormalities - do have behaviors or conditions strongly associated with developing HF - associated factors: hypertension diabetes coronary artery disease family history of cardiomyopathy personal history of alcohol abuse, rheumatic fever, or treatment with a cardiotoxic drug - should cease behaviors that cause HF risk, especially smoking and alcohol abuse B. STAGE B - no signs or symptoms of HF - structural heart disease that is strongly associated with development of HF - changes include: LV hypertrophy or fibrosis LV dilation or hypocontractility valvular heart disease previous myocardial infarction - goal is to prevent development of symptomatic HF - approach is to implement measures that can prevent further cardiac injury, retarding the progression of remodeling and LV dysfunction - specific measures include all for Stage A and treatment with an ACE inhibitor plus a beta blocker for all patients with a reduced ejection fraction, history of myocardial infarction or both C.

STAGE C - symptoms of HF - - including dyspnea, fatigue, peripheral edema, and distention of the jugular vein - structural heart disease Treatment Goals: relief of pulmonary and peripheral congestive symptoms improvement of functional capacity and quality of life slowing of cardiac remodeling and progression of LV dysfunction prolongation of life Drug Therapy:

Diuretics, ACE inhibitors, Beta Blockers, Digoxin

Drugs to Avoid:

antidysrhythmic agents, calcium channel blockers,

NSAIDs D.

STAGE D

- have advanced structural heart disease and marked symptoms of HF at rest, despite treatment with maximal doses of medications used in Stage C - best long-term solution is a heart transplant - management focuses largely on control of fluid retention - intake and output should be monitored closely - should weigh every day - patients should not be discharged until a stable and effective oral diuretic regimen has been established