Drugs for Heart Failure Flashcards Preview

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Flashcards in Drugs for Heart Failure Deck (105):
1

•impaired ability of the ventricle to fill with or eject blood

HEART FAILURE

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•inability of the heart to pump blood to meet the metabolic demands of the body

HEART FAILURE

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•formerly called CHF

HEART FAILURE

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HEART FAILURE
•common cause:

–Left systolic dysfunction secondary to CAD (~70%)

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•primary manifestations: HF

–dyspnea
–fatigue
–fluid retention

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–pulmonary congestion

•Left Ventricular Failure

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–pulmonary edema

•Left Ventricular Failure

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–dyspnea, orthopnea

•Left Ventricular Failure

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–systemic congestion

•Right Ventricular Failure

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–peripheral edema

•Right Ventricular Failure

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–jugular venous distention

•Right Ventricular Failure

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–due to NE → increased HR (can only increase O2 demand)

•tachycardia & increased contractility

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–increased preload → increased SV (leads to congestion)

•Frank-Starling mechanism

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–to redistribute blood flow (increases afterload)

•vasoconstriction

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–changes in cardiac muscle mass, size, shape, structure, function

•ventricular hypertrophy & remodelling

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GOALS OF PHARMACOLOGIC INTERVENTION

•To alleviate symptoms, slow disease progression, and improve survival

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•6 classes of drugs:


•1) inhibitors of the renin-angiotensin system
•2) ß-adrenoreceptor blockers
•3) diuretics
•4) direct vasodilators
•5) inotropic agents
•6) aldosterone antagonists

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BENEFICIAL EFFECTS OF DRUGS FOR HF

•Reduction of the load on the myocardium
•Decreased extracellular fluid volume
•Improved cardiac contractility
•Slowing the rate of cardiac remodeling

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•Agents of choice in HF

ACE INHIBITORS

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•Block ACE (conversion of angiotensin I to II)

ACE INHIBITORS

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•Diminish the rate of bradykinin inactivation

ACE INHIBITORS

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•Decrease vascular resistance, venous tone, BP

ACE INHIBITORS

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•Reduce preload and afterload -> increased cardiac output

ACE INHIBITORS

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•Indicated in patients with all stages of left ventricular failure

ACE INHIBITORS

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•Should be taken on an empty stomach

ACE INHIBITORS

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•Pro-drugs that require activation by hydrolysis via hepatic enzymes (except ______)

ACE INHIBITORS
Captopril

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• are adequately but incompletely absorbed following oral administration

ACE INHIBITORS

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•Monopeptide, orally active compounds that are extremely potent competitive antagonists of the AT1 receptor

ARBs

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•Advantage of more complete blockade of angiotensin action

ARBs

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•Do not affect bradykinin levels

ARBs

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•Similar actions with ACEIs but not therapeutically identical

ARBs

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•Alternative to the ACEIs

ARBs

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•All require only once-daily dosing

ARBs

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only ARB that undergoes extensive first-pass effect, along with conversion to its active metabolite

Losartan:

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•All are highly protein-bound

ARBs

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•All have large Vd (except ______)

candesartan

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•Ability to prevent the myocardial changes because of the chronic inactivation of the sympathetic nervous system –decreasing HR and inhibiting the release of renin

BETA-BLOCKERS

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•Prevent direct deleterious effects of NE on the cardiac muscle fibers -> decreasing remodeling, hypertrophy, and cell death

BETA-BLOCKERS

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is recommended for all patients with heart disease except those who are at high risk but have no symptoms and those who are in acute HF

BETA-BLOCKERS

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nonselective ß-adrenoreceptor antagonist that also blocks alpha-adrenoreceptors

•Carvedilol:

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long-acting ß1-selective antagonist


•Metoprolol:

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•Reduce morbidity and mortality associated with HF

Carvedilol and Metoprolol

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•Treatment should be started at low doses and gradually titrated to effective doses based on patient tolerance

Carvedilol and Metoprolol

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•Additional benefit of antihypertensive action

Carvedilol and Metoprolol

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•Relieve pulmonary congestion and peripheral edema

DIURETICS

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•Useful in reducing the symptoms of volume overload (e.g., orthopnea, PND)

DIURETICS

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•Decrease plasma volume -> decreased venous return to the heart (preload) -> decreased cardiac workload and oxygen demand

DIURETICS

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•Decrease afterload by reducing plasma volume decreased BP

DIURETICS

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relatively mild diuretics and lose efficacy if patient creatinine clearance is less than 50 mL/min

•Thiazide diuretics:

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used for patients who require extensive diuresis and those with renal insufficiency; most commonly used diuretics in HF

•Loop diuretics:

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–Overdoses can lead to profound hypovolemia

DIURETICS

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•Dilation of venous blood vessels leads to a decrease in cardiac preload by increasing the venous capacitance

DIRECT VASODILATORS

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reduce systemic arteriolar resistance and decrease afterload

•Arterial dilators

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commonly used venous dilators for patients with congestive HF

•Nitrates:

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if the patient is intolerant of ACEIs or ß-blockers, or if additional vasodilator response is required

•Hydralazine+ ISDN:

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enhance cardiac muscle contractility -> increased cardiac output

INOTROPIC DRUGS
•Positive inotropic agents

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–Result of an increased cytoplasmic Ca concentration that enhances the contractility of cardiac muscle

INOTROPIC DRUGS
•Positive inotropic agents

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•Digitalis or digitalis glycosides (digitalis/foxglove plant)

I. DIGITALIS GLYCOSIDES

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•Group of chemically similar compounds that can increase the contractility of the heart muscle

I. DIGITALIS GLYCOSIDES

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•Influence Na and Ca ion flows in the cardiac muscle -> increased contraction of AV myocardium (positive inotropic action)

I. DIGITALIS GLYCOSIDES

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•Narrow therapeutic index

I. DIGITALIS GLYCOSIDES

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most widely used agent digitalis glycoside

•Digoxin:

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•Digoxin (Lanoxin®)

DIGITALIS GLYCOSIDES

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•Digitalis purpurea, Digitalis lanata

DIGITALIS GLYCOSIDES

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•inhibit Na+/K+ - ATPase pump

DIGITALIS GLYCOSIDES

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•Increases the force of cardiac contraction -> decreased EDV -> increased efficiency of contraction (EF) -> improved circulation -> reduced sympathetic activity -> reduced peripheral resistance -> decreased HR

Digoxin

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•Increased vaga ltone -> decreased HR -> diminished myocardial oxygen demand

Digoxin

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•Slows down AV conduction velocity (use in AF)

Digoxin

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•Severe LVSD after initiation of ACEI and diuretic therapy

Digoxin

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•HF with atrial fibrillation


Digoxin

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•Only digitalis glycoside available in the US

Digoxin

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•Very potent, with a narrow margin of safety

Digoxin

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•Long half-life of ~36 hours

Digoxin

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•Mainly eliminated intact by the kidney, requiring dose adjustment based on CrCl

Digoxin

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•Large Vd: accumulates in muscle

Digoxin

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•Dosage based on lean BW

Digoxin

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•Loading dose regimen is used when acute digitalization is needed

Digoxin

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•Cardiac: arrhythmia (slowing of AV conduction associated with atrial arrhythmias)

Digoxin

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GI: anorexia, N/V

Digoxin

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•CNS: headache, fatigue, confusion, blurred vision, alteration of color perception, halos on dark objects

Digoxin

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PREDISPOSING FACTORS OF DIGOXIN TOXICITY

•Hypothyroidism
•Hypoxia
•Renal failure
•Myocarditis

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MANAGEMENT OF DIGOXIN TOXICITY

•Discontinuation of cardiac glycoside therapy
•Determination of serum K levels
•Oral K supplementation (if indicated)
•Close monitoring of digoxin levels in renal insufficiency -> dose adjustments
•Administration of antiarrhythmic drugs
•Digoxin immune Fab

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•Dobutamine and dopamine

II. BETA-ADRENERGIC AGONISTS

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•Intravenous inotropic agent administered at the hospital

II. BETA-ADRENERGIC AGONISTS

–250 mg/20 mL vial
–250 mg/250 mL pre-mix (1:1)
–500 mg/250 mL pre-mix (2:1)
•Dobutamine and dopamine

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•Positive inotropic effect and vasodilation

II. BETA-ADRENERGIC AGONISTS
•Dobutamine and dopamine

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•Treatment of acute HF

II. BETA-ADRENERGIC AGONISTS
•Dobutamine and dopamine

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III. PHOSPHODIESTERASE INHIBITORS



II. PHOSPHODIESTERASE INHIBITORS
•Inamrinone (formerly Amrinone)
•Milrinone

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•Long-term treatment = higher risk of mortality

II. PHOSPHODIESTERASE INHIBITORS
•Inamrinone (formerly Amrinone)
•Milrinone

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•Short-term IV milrinone: not associated with increased risk of mortality; symptomatic benefit in refractory HF

II. PHOSPHODIESTERASE INHIBITORS
•Inamrinone (formerly Amrinone)
•Milrinone

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•Direct antagonist of aldosterone -> prevents salt retention, myocardial hypertrophy, hypokalemia

ALDOSTERONE ANTAGONISTS (Spironolactone)

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•Reserved for the most advanced cases of HF

ALDOSTERONE ANTAGONISTS (Spironolactone)

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•AEs: GI disturbances (e.g., gastritis, peptic ulcer); CNS effects (lethargy, confusion); endocrine abnormalities (e.g., gynecomastia, decreased libido, menstrual irregularities)

ALDOSTERONE ANTAGONISTS (Spironolactone)

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•Competitive antagonist of aldosterone at mineralocorticoid receptors

ALDOSTERONE ANTAGONISTS (Eplerenone)

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•Lower incidence of endocrine-related SE due to reduced affinity for glucocorticoid, androgen, and progesterone receptors

ALDOSTERONE ANTAGONISTS (Eplerenone)

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•Reduces mortality in patients with LVSD and HF after acute MI

ALDOSTERONE ANTAGONISTS (Eplerenone)

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At risk for developingHF. No identified structural or functional abnormality; no signs and symptoms.

Stage A

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Developed structural heart diseasethat is strongly associated with the development of HF, but without signs and symptoms.

Stage B

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SymptomaticHF associated with underlying structural heart disease

Stage C

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Advanced structural heart disease and markedsymptoms of HF at rest despite maximal medical therapy

Stage D

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No limitation of physical activity. Ordinary physicalactivity does not cause undue fatigue, palpitation, or dyspnea

Class I

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Slight limitation of physical activity. Comfortableat rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea

Class II

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Marked limitation of physicalactivity. Comfortable at rest, but less than ordinary activity results in fatigue, palpitation, or dyspnea

Class III

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Unable to carry on anyphysical activity without discomfort. Symptoms at rest. If any physical activity is undertaken, discomfort is increased.

Class IV

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Stageof heart failurebased on structure and damage to heart muscle

ACC/AHAStages of Heart Failure

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Severity based on symptoms and physical activity

NYHA Functional Classification