Congestive Heart Failure Treatment Principles

Drugs Used for Treatment of Congestive Heart Failure

• Congestive heart failure is a progressive disease characterized by a gradual reduction in cardiac performance.
• Symptoms may occur only when metabolic demand increases (e.g., during exercise or stress).
• Patients may experience episodes of acute decompensation requiring hospitalization.

Lesson Outcomes

• Students will be able to describe therapeutic objectives for congestive heart failure treatment.
• Students will be able to classify drugs used in congestive heart failure and identify common drugs within each class.
• Students will be able to describe the mechanism of action, pharmacological effects, pharmacokinetic features, and therapeutic uses of drugs used in congestive heart failure. This should include common adverse effects.
• Students will be able to describe predisposing factors, symptoms, and treatments for digitalis toxicity with digibind.

What is Heart Failure?

• Heart failure is a condition where the heart cannot pump blood at the rate needed by the body's tissues. This may happen even when the heart is filling under pressure.
• In mild to moderate cases, symptoms only appear when metabolic demands increase (e.g., during exercise).
• It's a progressive disease indicated by gradual cardiac performance decline, punctuated by acute decompensation episodes and possible hospitalizations.

Pathophysiology of Heart Failure

• Factors that may exacerbate or originate heart failure in pre-existing heart disease include myocardial ischemia, infarctions, intercurrent illnesses, arrhythmia, inappropriate therapy reduction, or administration of drugs with negative inotropic/fluid-retaining properties (e.g., NSAIDs).
• Conditions like pulmonary embolism, increased metabolic demand (e.g., pregnancy, thyrotoxicosis, anemia), and intravenous fluid overload may contribute to the condition.
• Pathophysiology involves neurohumoral activation (e.g., renin-angiotensin-aldosterone system activation, resulting in vasoconstriction and fluid retention).

Therapeutic Objectives

• Improve quality of life by relieving symptoms and slowing progression.
• Delay death (mortality) by countering harmful compensatory mechanisms while addressing the underlying cause.
• Achieving these objectives entails five treatment principles: -1. Neurohumoral Modulation -2. Preload Reduction
  -3. Afterload Reduction -4. Increasing Cardiac Contractility -5. Heart Rate Reduction

Drug/Drug Classes Involved

• ACEIs, ARBs, β-blockers, Mineralocorticoid receptor antagonists (MRAs), loop diuretics, thiazide diuretics, K+-sparing diuretics, natriuretic peptides, direct vasodilators (e.g., nitrates), CAMP-dependent inotropes, cardiac glycosides, sympathomimetics/beta agonists, direct bradycardia agents.

ACEIs and ARBs

• ACE inhibitors (ACEIs) inhibit angiotensin-converting enzyme (ACE).
• Angiotensin II production decreases when ACE is inhibited. This reduces vasoconstriction and aldosterone production
• ACEI and ARBs can reduce blood pressure and afterload, but can not reduce preload significantly
• Angiotensin receptor blockers (ARBs) block angiotensin II receptors.

Pharmacological Basis of ACEI in CHF

• ACE inhibitors reduce sympathetic activation and improve symptoms by reducing afterload.
• They prevent the formation of angiotensin II, a vasoconstrictor crucial in heart failure.
• Increased bradykinin, a vasodilator, is also a consequence of ACE inhibition.
• Preload is reduced as a result of reducing aldosterone production, curbing salt and water retention.
• Prevention of cardiac remodeling, especially after a myocardial infarction (MI), is associated with ACEIs.

Pathophysiology of Ventricular Dysfunction in Cardiac Remodeling

• Cardiac remodeling involves molecular, cellular, and interstitial changes in the heart.
• Various factors, including inflammation and oxidative stress, play a role in the remodeling process.
• Drugs that have effects on cardiac remodeling include aldosterone antagonists, ACEIs, and ARBs.

Neurohumoral Activation and Sites of Action of Drugs Used in Heart Failure

• Drugs act on the renin-angiotensin-aldosterone system; ACE inhibitors, angiotensin II receptor blockers help counteract that.

Adverse Effects of ACEIs

• These include first-dose hypotension, hyperkalemia, angioedema, and dry cough.

What You Should Know?

• Start with a low dose at bedtime to avoid hypotension.
• Gradually increase dosages.
• Consult with your doctor about increasing dosages.
• Elderly patients may require hospitalization if they cannot manage their conditions at home.
• It is essential to check blood biochemistry, including urea and creatinine, electrolytes, weekly, especially for those taking concomitant potassium-sparing medications, and after each dose increase.
• Also, follow up on potassium levels to prevent potential side effects.

Beta-Adrenergic Receptor Antagonists

• Were once contraindicated due to their negative inotropic activity, but they are now included in modern treatment strategies for heart failure.
• β-blockers can now be used as add-on drugs in chronically stable patients, and are not recommended in acute heart failure.

Pharmacological Basis of Beta-blockers in CHF

• Beta-blockers reduce harmful compensatory mechanisms linked to high sympathetic tone in heart failure.
• They help in mitigating norepinephrine excess-induced effects, such as arrhythmias due to poor ejection fraction.
• Improve patient survival and decrease morbidity.
• Reduces hospitalizations and reduces mortality in general.

Aldosterone Antagonists/Potassium-Sparing Diuretics

• Block aldosterone receptors in renal tubules to reduce sodium and potassium excretion.
• Resultant reduction in heart failure mortality.
• Treatment use is to avoid excessive potassium depletion and enhance natriuretic effects.
• Possible side effect is hyperkalemia (excess potassium in the blood), especially in individuals taking ACE inhibitors, ARBs, and those with renal impairment.

Loop Diuretics

• Work in the loop of Henle, blocking sodium, potassium, and chloride reabsorption.
• Used to manage moderate to severe heart failure, pulmonary edema, and acute volume overload to reduce fluid overload, oedema, and associated symptoms.
• They can cause imbalance of electrolytes.

Thiazide Diuretics

• Inhibit sodium chloride reabsorption in the distal convoluted tubule.
• Used to manage mild heart failure.
• Reduce fluid overload and edema.
• Possible adverse effects include hypokalemia, worsened diabetes, magnesium depletion, increased serum lipids, and gout.

Nesiritide

• A recombinant brain natriuretic peptide (BNP) used mainly for acute heart failure.
• Increases cyclic GMP in smooth muscle cells, facilitating vasodilation and reducing venous/arteriolar tone, leading to preload and afterload reduction.
• It is short-acting and has a rapid onset, but a shorter duration of action.

Vasodilators

• Hydralazine and Nitrates are vasodilators.
• Hydralazine is an arteriolar dilator and nitrates are predominantly venodilators.
• Usually used in combination for improved efficacy.
• They are useful due to low cost, but long-term use causes tolerance.

Inotropes

• Used for increasing the force of cardiac contraction in patients with heart failure.
• Agents like digoxin, dopamine, dobutamine, and milrinone increase cardiac contractility.

Digoxin

• Increases cardiac contractility.
• Low doses stimulate vagal efferents, decreasing sympathetic tone and conduction velocity, which is clinically useful for atrial fibrillation.
• High doses may result in arrhythmias.

Digoxin Toxicity

• Management can involve reducing or stopping the drug, managing extreme bradycardia.
• Tachycardia and hypokalemia, and electrolyte interactions (especially potassium, magnesium, and calcium imbalances due to diuretic use).

Dopamine

• Low doses increase renal blood flow and maintain glomerular filtration rate (GFR).
• Intermediate doses stimulate cardiac beta-1 receptors for enhanced contractility.
• High doses cause peripheral arterial and venous constriction by stimulating alpha receptors.

Dobutamine

• A beta-1 receptor agonist that mainly used for acute heart failure with systolic dysfunction.
• Stimulates myocardial contractility (positive inotropy).
• Side effects include tachycardia and increased myocardial oxygen consumption.

Bipyridines (Milrinone)

• Inhibit phosphodiesterase (PDE-3), increasing cyclic AMP (cAMP) levels.
• Positive inotropic and chronotropic effects leading to improved contractility.
• Vasodilatory effects lower both preload and afterload.

Levosimendan

• Acts as a calcium sensitizer that enhances contractility and a vasodilator.
• Sensitize troponin C to calcium and inhibits phosphodiesterase (PDE) enzymes.

Ivabradine

• A selective inhibitor of the If current in the sinoatrial node.
• Use in patients with heart failure and stable angina who do not tolerate beta-blockers.
• Used to slow heart rate.

Management of Acute Heart Failure(Acute Pulmonary Edema)

• Key actions include patient positioning (sitting up), high-flow oxygen administration, continuous positive airway pressure (CPAP), nitrate administration, and loop diuretics.

Prescribed and Recommended Textbooks

• The list provides multiple sources, including Goodman & Gilman's and Katzung's Basic and Clinical Pharmacology, along with other authoritative publications.

This quiz tests your knowledge on the therapeutic objectives and principles in the treatment of congestive heart failure. You will explore drug classifications, common medications, and their effects in managing heart failure. Perfect for medical students or healthcare professionals seeking to reinforce their understanding.