Module 2: Drugs for Heart Failure Flashcards
Two Major Forms of Heart Failure
- Heart failure (HF) with left ventricular (LV)
systolic dysfunction - Diastolic heart failure, also known as heart
failure with preserved LV ejection fraction
Note: In this chapter, we focus primarily
on the treatment of form #1
What causes/contributes to heart failure?
Inadequate tissue perfusion
Volume overload
Chronic hypertension
Myocardial infarction
Valvular heart disease
Coronary artery disease
Congenital heart disease
Dysrhythmias
Aging of the myocardium
Cardiac remodeling
Physiologic adaptations to reduced cardiac
output (CO)
Cardiac dilation
Increased sympathetic tone
Water retention and increased blood volume
Natriuretic peptides
List of drugs for heart failure
Diuretics
RAAS inhibitors
Angiotensin-converting enzyme inhibitors
Angiotensin II receptor blockers
Aldosterone antagonists
Direct renin inhibitors
Beta blockers
Digoxin
Dopamine
Hydralazine
Diuretics
Thiazide diuretics
-work in the distal convoluted tubule of the kidney. They inhibit the sodium-chloride transporter, leading to increased excretion of sodium and water
-Generally used in mild to moderate cases of heart failure. They are less potent than loop diuretics but are effective in reducing fluid overload.
Examples: Hydrochlorothiazide, chlorthalidone.
High-ceiling (loop) diuretics
-Loop diuretics act on the ascending limb of the loop of Henle in the kidney. They inhibit the sodium-potassium-chloride transporter, leading to a significant increase in the excretion of sodium, chloride, and water.
-called “high-ceiling” because their diuretic effect is greater and continues to increase with higher doses. They are often used in more severe cases of heart failure or when there is significant fluid retention.
Examples: Furosemide, bumetanide, torsemide.
Potassium-sparing diuretics
-work by either blocking aldosterone receptors (mineralocorticoid receptor antagonists) or by directly affecting sodium channels in the collecting ducts of the kidney. They help the body retain potassium while still excreting sodium and water.
-Often used in combination with other diuretics to mitigate potassium loss. They can be particularly beneficial in heart failure patients who are at risk of developing hypokalemia.
Examples: Spironolactone, eplerenone (aldosterone antagonists), amiloride, and triamterene.
Drugs that Inhibit the RAAS
They block an enzyme in your body (angiotensin-converting enzyme) that’s involved in producing a substance called angiotensin II, which normally tightens your blood vessels.
Hemodynamic Benefits (How they help your heart and blood flow):
-Arteriolar Dilation: They help your small arteries relax or widen (dilate). This makes it easier for blood to flow and lowers blood pressure.
-Venous Dilation: They also help the veins relax, which decreases the amount of work your heart has to do.
Suppression of Aldosterone Release: Aldosterone is a hormone that makes your body hold onto salt and water. ACE inhibitors reduce its release, helping to lower blood pressure and reduce the strain on your heart.
Impact on Cardiac Remodeling:
-“Cardiac remodeling” refers to changes in the size, shape, and function of the heart after injury (like a heart attack) or due to heart disease.
-ACE inhibitors can prevent or reverse some of these changes, which is really good for the heart. It means your heart can pump blood more efficiently and stay healthier.
Adverse effects
* Hypotension
* Hyperkalemia
* Intractable cough - severe cough that resists treatment
* Angioedema - deep swelling beneath skin’s surface, often around eyes and lips. Sometimes on hands, feet, or genitals
* Renal failure if patient has bilateral renal artery stenosis
* Can cause fetal injury
Angiotensin II receptor blockers (ARBs)
Clinical trials have shown that ARBs improve LV
ejection fraction, reduce HF symptoms, increase
exercise tolerance, decrease hospitalization, enhance quality of life, and reduce mortality
Aldosterone antagonists
Spironolactone [Aldactone] and eplerenone [Inspra]
Current studies recommend adding an aldosterone antagonist to standard HF therapy in patients with moderately severe or severe symptoms
Direct renin inhibitors (DRIs)
Benefits in HF should be equal to those of ACE
inhibitors or ARBs
Aliskiren [Tekturna] is being tested in HF
Not yet approved for HF treatment
Lisinopril: Often prescribed for high blood pressure and heart failure, and it’s also used in patients who have had a heart attack.
Enalapril: Used to treat high blood pressure, heart failure, and sometimes kidney disease in people with diabetes.
Ramipril: Commonly used for high blood pressure, heart failure, and to improve survival after a heart attack.
Captopril: One of the first ACE inhibitors developed, used for high blood pressure, heart failure, and kidney problems caused by diabetes.
Benazepril: Mainly prescribed for high blood pressure and also sometimes for heart failure.
Beta Blockers
Action
With careful control of dosage, can improve patient’s status
Protect from excessive sympathetic stimulation
Protect against dysrhythmias
Adverse effects
Fluid retention or worsening of HF
Fatigue
Hypotension
Bradycardia or heart block
Digoxin and Cardiac Glycosides
Positive inotropic actions
Increase myocardial contractile force
Alter electrical activity of the heart
Favorably affect neurohormonal systems
Second-line agents
Inotropic Agents
Sympathomimetics
Sympathomimetics are a class of drugs that mimic the effects of the sympathetic nervous system, often referred to as the “fight or flight” response. Dopamine, marketed under the brand name Intropin, is a well-known sympathomimetic drug.
Dopamine [Intropin]
* Catecholamine
Dopamine is a catecholamine, a type of hormone and neurotransmitter naturally produced in the body. As a medication, it is synthesized for medical use.
- Activates beta1-adrenergic receptors in the heart,
kidney, and blood vessels
Dopamine activates beta1-adrenergic receptors primarily found in the heart. Activation of these receptors increases heart rate and contractility, which can improve cardiac output (the volume of blood the heart pumps per minute). - Increases heart rate
- Dilates renal blood vessels
At moderate doses, dopamine dilates renal (kidney) blood vessels. This can help improve kidney function and urine output, which is particularly important in critically ill patients or those with compromised kidney function.
The dilation of renal blood vessels can also help maintain kidney perfusion, especially in states of shock where blood flow to the kidneys may be compromised. - Activates alpha1 receptors
At higher doses, dopamine activates alpha1 receptors, which are located in various blood vessels. Activation of these receptors causes vasoconstriction, or narrowing of the blood vessels, which can increase blood pressure.
This effect is useful in treating certain conditions like hypotension (low blood pressure) and shock, where blood pressure needs to be increased to maintain adequate organ perfusion.
Inotropic Agents Cont
Dobutamine:
-Synthetic Catecholamine: Dobutamine is a man-made drug that mimics some of the actions of natural catecholamines (like dopamine) in the body.
-Selective Activation of Beta1-Adrenergic Receptors: It primarily works on beta1-adrenergic receptors in the heart. Activation of these receptors increases the heart’s contractility (the strength of its contractions) and heart rate.
Use: Dobutamine is often used in situations like acute heart failure or cardiogenic shock, where the heart needs help to pump more effectively. It’s particularly useful because it improves cardiac output (the volume of blood the heart pumps) without significantly increasing heart rate.
Phosphodiesterase Inhibitors (Milrinone [Primacor]):
-Inodilator: Milrinone is often referred to as an inodilator because of its two primary actions: it increases myocardial contractility (inotropy) and promotes vasodilation (widening of blood vessels).
Mechanism: It works by inhibiting the enzyme phosphodiesterase-3 in cardiac and vascular smooth muscle. This action increases the amount of calcium available for myocardial contraction, thereby enhancing the heart’s pumping ability, while also relaxing vascular smooth muscles, leading to vasodilation.
Use: Milrinone is reserved for patients with a severe reduction in cardiac output, which leads to decreased organ perfusion. It’s used in critical care settings, like severe heart failure or cardiogenic shock, where the heart is struggling to maintain an adequate output.
Side Effects: Important side effects include the potential for arrhythmias (irregular heartbeats) and myocardial ischemia (reduced blood supply to the heart muscle).
Ivabradine (Corlanor)
For use in patients with stable, symptomatic
heart failure with:
LVEF <35%
Sinus rhythm
Heart rate > 70 BPM
Can be used for patient’s who have a
contradindication to beta blocker use
Vasodilators
Vasodilators are a class of medications that relax and widen (dilate) blood vessels, improving blood flow and reducing the workload on the heart.
*Isosorbide Dinitrate plus Hydralazine:
-This combination is often used in chronic management, particularly for heart failure.
Isosorbide dinitrate is a nitrate that helps widen blood vessels, while hydralazine relaxes arterial walls. Together, they help improve blood flow and reduce the heart’s workload.
*Intravenous Vasodilators for Acute Care:
These are used in hospital settings for immediate relief of symptoms related to heart conditions like acute heart failure or angina (chest pain).
*Nitroglycerin:
A commonly used vasodilator for acute heart conditions, especially angina.
*Principal Adverse Effects:
-Hypotension (Low Blood Pressure): Nitroglycerin can cause a significant drop in blood pressure.
-Reflex Tachycardia: As a response to low blood pressure, the heart rate may increase (tachycardia).
*Sodium Nitroprusside [Nitropress]:
Often used in hypertensive emergencies or acute heart failure because it’s a potent vasodilator.
-Principal Adverse Effect:
-Profound Hypotension: It can cause a very rapid and significant drop in blood pressure.
*Nesiritide [Natrecor]:
Used in the treatment of acute decompensated heart failure.
-Principal Adverse Effect:
-Symptomatic Hypotension: Nesiritide can lead to a drop in blood pressure, which may cause symptoms like dizziness or fainting.
Cardiac (Digitalis) Glycosides
**Digoxin, known by brand names such as Lanoxin, Lanoxicaps, and Digitek, is a cardiac glycoside with a long history of use in treating certain heart conditions
Naturally Occurring Compound:
-Digoxin is derived from the leaves of the digitalis plant (foxglove). It’s been used for centuries to treat heart conditions.
Effects on the Heart:
-Mechanical Properties: Digoxin increases the strength of heart muscle contractions. This helps the heart pump more effectively, which is particularly beneficial in heart failure.
-Electrical Properties: It also has specific effects on the heart’s electrical conduction system. It can slow the heart rate and improve the rhythm, making it useful in conditions like atrial fibrillation.
-Increased Cardiac Output:
By enhancing myocardial contractility (the ability of the heart muscle to contract), digoxin increases cardiac output, which is the amount of blood the heart pumps in a minute. This can be helpful in patients with heart failure, where the heart’s pumping ability is impaired.
-Adverse Effects:
Severe Dysrhythmias: One of the major concerns with digoxin is its potential to cause abnormal heart rhythms (dysrhythmias). These can be serious and even life-threatening.
-Narrow Therapeutic Index: Digoxin has a narrow therapeutic window, meaning the difference between a therapeutic dose and a toxic dose is small. This necessitates careful dosing and regular monitoring of blood levels.
Other potential side effects include gastrointestinal disturbances, neurological effects, and visual disturbances.
Digoxin [Lanoxin]
***Positive Inotropic Action:
“Inotropic action” refers to the effect on the heart’s force of contraction. A “positive inotropic action” means that digoxin increases the strength of the heart’s contractions.
This helps the heart pump more effectively, which is particularly useful in conditions like heart failure.
Increases Force of Ventricular Contraction and Myocardial Contractility:
By increasing the force with which the ventricles (the heart’s main pumping chambers) contract, digoxin improves the overall ability of the heart to pump blood (myocardial contractility).
This is crucial for patients whose heart muscle is weakened.
Relationship of Potassium to Inotropic Action:
Digoxin’s effectiveness is closely linked to the body’s potassium levels. If potassium levels are too high or too low, it can affect how well digoxin works and might increase the risk of side effects.
Maintaining normal potassium levels is important for the safe and effective use of digoxin.
Hemodynamic Benefits:
Increased Cardiac Output: As digoxin strengthens heart contractions, it helps increase the volume of blood the heart pumps, known as cardiac output.
Decreased Sympathetic Tone: It can reduce the activity of the sympathetic nervous system (the body’s “fight or flight” response), which is often overactive in heart failure.
Increased Urine Production: By improving heart function, digoxin can help reduce fluid buildup in the body, leading to increased urine production.
Decreased Renin Release: It can also help decrease the release of renin, a hormone that can contribute to fluid retention and high blood pressure, both of which are concerns in heart failure.
Neurohormonal Benefits:
Modulates Neurohormonal System Activity: Digoxin helps balance the activity of the body’s neurohormonal system, which includes various hormones and nerve signals that control heart function.
Suppresses Renin Release in the Kidney: By reducing renin release, digoxin helps control blood pressure and fluid balance. Renin is an enzyme that plays a key role in the body’s regulation of blood pressure, blood volume, and sodium balance.
Decreases Sympathetic Outflow from the CNS: The sympathetic nervous system, which increases heart rate and blood pressure during stress (“fight or flight” response), is less activated. This decrease in sympathetic outflow can reduce the workload on the heart.
Increases Sensitivity of Cardiac Baroreceptors: Baroreceptors are sensors in blood vessels that detect blood pressure and help regulate it. By increasing their sensitivity, digoxin can help stabilize blood pressure and heart rate.
Electrical Effects:
Alters Electrical Properties of the Heart: Digoxin has a direct impact on the electrical conduction system of the heart, which controls the heart rhythm.
Increases Firing Rate of Vagal Fibers: The vagus nerve plays a critical role in slowing the heart rate. Digoxin increases the activity of this nerve, which can slow down the heart rate, beneficial in conditions like atrial fibrillation.
Increases Responsiveness of Sinoatrial (SA) Node to Acetylcholine: The SA node is the natural pacemaker of the heart. By increasing its responsiveness to acetylcholine (a neurotransmitter that reduces heart rate), digoxin can further help in slowing down an excessively fast heart rate.
Digoxin (Lanoxin) Adverse Effects
Adverse Effects - Cardiac Dysrhythmias:
Digoxin can cause various types of heart rhythm disturbances, ranging from minor irregularities to severe arrhythmias that can be life-threatening.
Predisposing Factors:
**Hypokalemia (Low Potassium Levels): Low potassium levels can enhance the effects of digoxin on the heart, increasing the risk of dysrhythmias.
**Elevated Digoxin Level:
Digoxin has a narrow therapeutic range, meaning the difference between an effective dose and a toxic dose is small. Overdose or elevated levels of digoxin in the blood can lead to dysrhythmias.
Heart Disease: Patients with underlying heart disease are more susceptible to digoxin-induced dysrhythmias.
Diagnosing Digoxin-Induced Dysrhythmias:
Diagnosis typically involves monitoring heart rhythm through an electrocardiogram (ECG), assessing for symptoms of digoxin toxicity, and measuring blood levels of digoxin.
Symptoms of toxicity can include nausea, vomiting, dizziness, blurred vision, and confusion, alongside specific ECG changes.
Managing Digoxin-Induced Dysrhythmias:
Immediate Reduction or Discontinuation of Digoxin: If dysrhythmias are suspected to be caused by digoxin toxicity, reducing the dose or stopping the drug is often the first step.
Correcting Electrolyte Imbalances: Addressing low potassium or magnesium levels, which can contribute to the risk of dysrhythmias, is crucial.
Medications: In some cases, medications may be required to stabilize the heart rhythm.
Antidote for Severe Cases: In severe cases of digoxin toxicity, an antidote (digoxin immune Fab) can be used to bind and neutralize digoxin, reducing its effects on the heart
Noncardiac adverse effects
* Anorexia, nausea, vomiting, fatigue
Digoxin (Lanoxin) Drug Interactions
**Drug interactions
Diuretics
ACE inhibitors and ARBs
Sympathomimetics
Quinidine
Verapamil
**Pharmacokinetics
Absorption
Distributed widely and crosses placenta
Eliminated primarily by renal excretion
Half-life about 1.5 days
