Podcast
Questions and Answers
Which of the following is NOT a major cardiovascular, pulmonary, or renal complication of heart failure?
Which of the following is NOT a major cardiovascular, pulmonary, or renal complication of heart failure?
Which of the following is a therapeutic target for treating heart failure?
Which of the following is a therapeutic target for treating heart failure?
Which of the following classes of drugs is NOT used to treat heart failure?
Which of the following classes of drugs is NOT used to treat heart failure?
Which of the following is an example of a RAAS inhibitor used to treat heart failure?
Which of the following is an example of a RAAS inhibitor used to treat heart failure?
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Which of the following classes of drugs directly increases the force of heart contractions?
Which of the following classes of drugs directly increases the force of heart contractions?
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Which of the following is an example of a diuretic used to treat heart failure?
Which of the following is an example of a diuretic used to treat heart failure?
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Which of the following drug classes primarily targets reducing preload in heart failure treatment?
Which of the following drug classes primarily targets reducing preload in heart failure treatment?
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What is a key difference in the drug treatment approach between acute and chronic heart failure?
What is a key difference in the drug treatment approach between acute and chronic heart failure?
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What is the primary goal of drug therapy in heart failure?
What is the primary goal of drug therapy in heart failure?
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Which of the following classes of drugs are primarily used to reduce afterload in heart failure treatment?
Which of the following classes of drugs are primarily used to reduce afterload in heart failure treatment?
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Which of the following drugs is a direct-acting arterial vasodilator used to reduce afterload in heart failure?
Which of the following drugs is a direct-acting arterial vasodilator used to reduce afterload in heart failure?
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Which of the following drugs is a venodilator used to reduce preload in heart failure?
Which of the following drugs is a venodilator used to reduce preload in heart failure?
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What is the mechanism of action of ACE inhibitors in heart failure treatment?
What is the mechanism of action of ACE inhibitors in heart failure treatment?
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Which of the following drugs is an example of an angiotensin receptor neprilysin inhibitor (ARNI)?
Which of the following drugs is an example of an angiotensin receptor neprilysin inhibitor (ARNI)?
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How do beta-blockers improve outcomes in heart failure?
How do beta-blockers improve outcomes in heart failure?
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What is the primary mechanism by which diuretics improve symptoms of heart failure?
What is the primary mechanism by which diuretics improve symptoms of heart failure?
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Which of the following is a common side effect of ACE inhibitors?
Which of the following is a common side effect of ACE inhibitors?
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What is a primary mechanism of action of dopamine when administered in low doses?
What is a primary mechanism of action of dopamine when administered in low doses?
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Which of the following is NOT a characteristic of dobutamine?
Which of the following is NOT a characteristic of dobutamine?
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What is the physiological target of SGLT2 inhibitors in heart failure treatment?
What is the physiological target of SGLT2 inhibitors in heart failure treatment?
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Which of the following statements accurately describes the use of sympathomimetic inotropic drugs in heart failure?
Which of the following statements accurately describes the use of sympathomimetic inotropic drugs in heart failure?
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What is the primary mechanism of action of milrinone, a phosphodiesterase (PDE3) inhibitor?
What is the primary mechanism of action of milrinone, a phosphodiesterase (PDE3) inhibitor?
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Which of the following accurately describes a characteristic of cardiac glycosides, such as digoxin?
Which of the following accurately describes a characteristic of cardiac glycosides, such as digoxin?
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What is the primary mechanism of action of carvedilol?
What is the primary mechanism of action of carvedilol?
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Which diuretic is primarily used for treating congestive heart failure (CHF)?
Which diuretic is primarily used for treating congestive heart failure (CHF)?
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What effect do beta-agonists have in acute heart failure?
What effect do beta-agonists have in acute heart failure?
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What is a potential problem associated with using loop diuretics?
What is a potential problem associated with using loop diuretics?
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Why are sympathomimetics typically used in acute failure and not chronic failure?
Why are sympathomimetics typically used in acute failure and not chronic failure?
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Which type of diuretic is considered K+-sparing?
Which type of diuretic is considered K+-sparing?
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What is a primary benefit of using aldosterone antagonists in CHF?
What is a primary benefit of using aldosterone antagonists in CHF?
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Which receptor affinity is higher for dopamine?
Which receptor affinity is higher for dopamine?
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Which inotropic drug class is primarily used for refractory heart failure?
Which inotropic drug class is primarily used for refractory heart failure?
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What is the primary action of diuretics in managing CHF?
What is the primary action of diuretics in managing CHF?
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Study Notes
Heart Failure Drugs - Lecture 09
- Heart failure drugs aim to improve cardiac function and reduce symptoms, decreasing morbidity and mortality.
- Addressing underlying issues (e.g., valve disease, CAD, arrhythmias) is crucial.
- Reducing clinical symptoms and morbidity (pulmonary congestion, systemic edema, dyspnea).
- Improving cardiovascular function (organ perfusion, cardiovascular functional reserve).
- Reducing mortality.
Learning Objectives
- Understanding major cardiovascular, pulmonary, and renal complications of heart failure.
- Defining therapeutic targets and goals for treating heart failure.
- Describing how different drug classes (vasodilators, RAAS inhibitors, beta-blockers, inotropics, diuretics, SGLT2 inhibitors) are used in heart failure treatment, with examples of specific drugs.
- Differentiating drug treatment strategies for both acute and chronic heart failure, and comparing treatment between HFrEF and HFpEF.
Cardiovascular, Pulmonary, and Renal Signs/Symptoms
- Reduced cardiac output and organ perfusion.
- Reduced exercise tolerance.
- Dyspnea.
- Pulmonary edema.
- Impaired lung gas exchange.
- Fluid retention (increased blood volume).
- Renal sodium retention.
- Elevated systemic vascular resistance.
- Sympathetic activation.
- Cardiac remodeling.
- Arrhythmias.
Drug Treatment - Physiological Targets
- Renin-angiotensin-aldosterone system (RAAS) inhibitors (ACEIs, ARBs, ARNIs) to reduce afterload, preload, blood volume, and remodeling.
- Cardiac sympathetic activation reduction with beta-blockers to reduce remodeling and arrhythmias.
- Volume overload and edema reduction with diuretics to reduce blood volume, venous pressures, and preload.
- SGLT2 inhibitors are included to benefit cardiac metabolic function.
Vasodilators
- RAAS inhibitors, neprilysin inhibitors, and direct-acting arterial and venous dilators.
Vasodilator Effects on Frank-Starling Curves
- Mixed vasodilators reduce afterload and preload, impacting stroke volume and ejection fraction (EF).
- Arterial vasodilators reduce afterload (e.g., hydralazine).
- Venous vasodilators reduce preload (e.g., isosorbide dinitrate).
Reducing Afterload in Systolic Dysfunction
- Reducing afterload with an arterial vasodilator drug leads to decreased end-systolic volume (ESV), end-diastolic volume (EDV), improved stroke volume, and improved ejection fraction.
- Failing hearts are more responsive to afterload changes than normal hearts.
Specific Drugs: ACE Inhibitors
- MOA: Block the formation of angiotensin II.
- Actions: Dilate arteries and veins, reduce sympathetic activity, decrease vasopressin release, and attenuate cardiac remodeling.
- Examples: lisinopril and enalapril.
Specific Drugs: ARBs
- MOA: Block angiotensin II type 1 (AT1) receptors.
- Actions: Similar to ACEIs in reducing afterload, preload, and remodeling.
- Examples: valsartan and losartan.
Specific Drugs: Neprilysin Inhibitors
- MOA: Inhibit neprilysin, increasing circulating natriuretic peptide (ANP), attenuating the RAAS system, and dilating vessels.
- Sacubitril (combined with valsartan) is an ARNI used in acute heart failure.
Specific Drugs: Hydralazine and Isosorbide Dinitrate
- Hydralazine: Direct-acting arterial vasodilator, decreasing afterload.
- Isosorbide dinitrate: Nitrodilator primarily dilating veins, reducing preload.
Beta-blockers
- Traditionally considered contraindicated in heart failure.
- Newer beta-blockers show efficacy in reducing risk of hospitalization and death.
- Benefits are noted after several months, and are commonly used with diuretics and ACE inhibitors.
Beta-blockers in CHF
- Specific drugs: carvedilol, metoprolol, and other beta blockers.
- Rationale: Excessive sympathetic activation in heart failure downregulates beta-1 receptors, reducing inotropic reserve.
Diuretics
- Increase Na+ and H2O excretion by kidneys.
- Actions: Reduce blood volume, CVP, ventricular preload, and pulmonary and systemic edema; and reduce systemic vascular resistance (SVR) with prolonged therapy.
- Potential problems: potassium loss, excessive volume reduction.
- Examples: furosemide (loop diuretic), thiazide diuretics, and potassium-sparing diuretics such as spironolactone and eplerenone.
Cardiostimulatory (Inotropic) Drugs
- Beta-agonists, PDE inhibitors, and digoxin.
- Drugs are used for patients with refractory, late-stage heart failure and acute cardiogenic shock.
Sympathomimetics
- Mimic the effects of sympathetic activation by stimulating beta-adrenoceptors and increasing intracellular calcium.
- Used in acute heart failure except in end-stage.
Dopamine
- Immediate precursor for norepinephrine synthesis in sympathetic nerve terminals.
- Low doses: cause systemic vasodilation and renal vasodilation, positive inotropy and chronotropy.
- High doses: α1-mediated vasoconstriction, increasing systemic resistance and producing hypertension.
Dobutamine (Dopamine Analog)
- Primarily beta-1 adrenoceptors.
- Used in acute heart failure, cardiogenic shock, and refractory heart failure.
- Short half-life, loss of efficacy with beta-1 receptor downregulation, and potential arrhythmogenicity.
Inodilators – phosphodiesterase (PDE3) inhibitors
- MOA: Increase cAMP levels in the heart and vasculature.
- Actions: Systemic vasodilation, mild-to-moderate positive inotropy, but often have increased chronic mortality as well as the potential for arrhythmias.
- Used in acute heart failure.
Cardiac Glycosides (digoxin)
- Inhibits Na+/K+-ATPase, increasing intracellular Ca++.
- Stimulates inotropy, increases ejection fraction, and decreases heart rate.
- Inhibits sympathetic activity. -Low therapeutic index.
Pharmacokinetics
- Digoxin has a half-life of 40 hours and is eliminated by the kidneys.
- Digitalization (reaching steady-state without loading doses) takes 5-7 days.
- Renal function and lean body mass are essential considerations.
- Toxicity increased by decreased potassium, magnesium, and increased calcium.
SGLT2 Inhibitors
- Most recent class used in heart failure, primary use for type 2 diabetes.
- MOA: Inhibit sodium-glucose co-transporter-2 (SGLT2) in the kidneys, increasing glucose excretion and promoting renal sodium and water excretion (natriuresis), lowering arterial blood pressure, and improving diastolic function.
Acute vs. Chronic Therapy in HFrEF
- Acute Systolic Failure: loop diuretics, arterial and mixed vasodilators, sympathomimetics (beta agonists), and PDE inhibitors.
- Chronic Systolic Failure: diuretics (usually a loop diuretic), K+-sparing diuretics, ACEI, ARB, ARNI, newer beta-blockers, digoxin, and SGLT2 inhibitors.
HFpEF: Drug Treatment Guidelines
- No clear guidelines; drugs primarily treat comorbidities (e.g., hypertension, atrial fibrillation, diabetes).
- Beta-blockers and calcium-channel blockers (e.g., verapamil).
- SGLT2 inhibitors.
- Aldosterone receptor antagonists.
- Diuretics for severe edema.
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Description
Test your knowledge on the pharmacological treatment of heart failure. This quiz covers drug classes, therapeutic targets, and their effects on the cardiovascular system. Assess your understanding of key concepts related to managing heart failure through medication.
