Learning Outcomes
By the end of this section, you should be able to:
- 19.6.1 Identify the characteristics of adjunct medications used to treat heart failure.
- 19.6.2 Explain the indications, actions, adverse reactions, and interactions of adjunct medications used to treat heart failure.
- 19.6.3 Describe nursing implications of adjunct medications used to treat heart failure.
- 19.6.4 Explain the client education related to adjunct medications used to treat heart failure.
Hydralazine and Isosorbide Dinitrate
Hydralazine and isosorbide dinitrate (BiDil) are administered as a combination drug in clients with heart failure who have optimized therapy with other medications but still have a low ejection fraction and/or symptoms. This drug combination has been shown to reduce mortality in Black clients with heart failure (Heidenreich et al., 2022). Research has not shown a decreased mortality in clients with heart failure who are not Black, but there may be some benefit to adding hydralazine and isosorbide dinitrate or to using this therapy if clients are not able to tolerate first-line therapy.
The combination of hydralazine and isosorbide dinitrate causes vasodilation, which decreases afterload, or the amount of force that the heart must pump against. Hydralazine directly vasodilates arterioles. Although the mechanism of action is not well understood, it is thought to decrease calcium release in the smooth muscles around arterioles. Because calcium is an essential component of muscle contraction, if less calcium is available, then the smooth muscle will contract less and the arteriole will not be constricted.
Isosorbide dinitrate is a part of the nitrate drug classification that was discussed in Antihypertensive and Antianginal Drugs. Nitrates cause the release of nitric oxide within the endothelium of blood vessels. Nitric oxide causes a series of events that ultimately lead to vasodilation.
Adverse Effects and Contraindications
Adverse effects include orthostatic hypotension, tachycardia, paradoxical bradycardia, flushing, peripheral edema, nausea/vomiting, headache (nitrates), blurred vision, drug-induced lupus erythematosus, hemolytic anemia, and glomerulonephritis.
Contraindications include allergy to nitrates and use with phosphodiesterase type 5 (PDE5) inhibitors.
Table 19.17 is a drug prototype table featuring hydralazine and isosorbide dinitrate. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
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Drug Class Arteriolar vasodilator/nitrate vasodilator Mechanism of Action Hydralazine directly vasodilates arterioles by causing smooth muscle relaxation. Isosorbide dinitrate causes the release of nitric oxide, which ultimately leads to vasodilation. |
Drug Dosage Heart failure: 20 mg isosorbide dinitrate with 37.5 mg hydralazine orally 3 times daily; maximum dose: 40 mg isosorbide dinitrate with 75 mg hydralazine orally 3 times daily. |
| Indications Adjunct treatment to standard therapy for self-identified Black clients with heart failure and/or clients who are not able to tolerate standard therapy Therapeutic Effects Lowers blood pressure, which decreases afterload |
Drug Interactions Phosphodiesterase type 5 (PDE5) inhibitors Food Interactions No significant interactions |
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Adverse Effects Orthostatic hypotension Dizziness Tachycardia Paradoxical bradycardia Flushing Peripheral edema Nausea/vomiting Headache (nitrates) Blurred vision Drug-induced lupus erythematosus Hemolytic anemia Glomerulonephritis |
Contraindications PDE5 inhibitors Allergy to nitrates |
Safety Alert
Hydralazine
Nitrates can cause hypotension; nitrates in combination with hydralazine can cause significant hypotension. This medication should not be taken with PDE5 inhibitors because this can lead to profound hypotension.
Nursing Implications
The nurse should do the following for clients who are taking hydralazine/isosorbide dinitrate:
- Assess the client’s drug and herbal supplements because significant hypotension may occur when used in conjunction with nitrates.
- Monitor the client’s blood pressure when initiating hydralazine/isosorbide dinitrate, and do not administer the medication if systolic blood pressure is less than 90 mm Hg.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking hydralazine/isosorbide dinitrate should:
- Monitor for signs and symptoms of low blood pressure such as dizziness or lightheadedness.
- Get up slowly during the first couple of days of taking the medication in case of orthostatic hypotension.
The client taking hydralazine/isosorbide dinitrate should not:
- Take erectile dysfunction medications with this medication because they also contain a nitrate.
Cardiac Glycosides
Cardiac glycosides used to be a first-line therapy in heart failure. Over the years, medications that are safer and more efficacious have been introduced on the market. However, cardiac glycosides may be used as adjunct therapy if first-line medications for heart failure have been optimized and the client still has a reduced ejection fraction and/or symptoms.
Digoxin is the only cardiac glycoside used in heart failure. It affects the sodium-potassium ATPase pump in such a way that causes more calcium to enter the cardiac myocyte. If there is more calcium, then the force of contraction is stronger. Because of this, digoxin is referred to as a positive inotrope. Digoxin also stimulates the parasympathetic nervous system, which affects the electrical conduction system of the heart. Parasympathetic stimulation causes the heart to beat less often. This means that there is a longer time for ventricular filling (longer diastole). This helps the heart since the cardiac myocytes receive oxygenated blood during diastole.
Digoxin can have complicated dosage instructions. There often is a loading dose and then a maintenance dose, and factors such as body weight, age, renal function, and concomitant drugs are part of the dosing consideration.
Adverse Effects and Contraindications
Adverse effects include fatal cardiac arrhythmias, sinus bradycardia, sinoatrial block, visual disturbances (yellow or green halo around lights), atrial tachycardia, and rash.
Digoxin has a narrow therapeutic index and a high potential for toxicity. Signs and symptoms of digoxin toxicity include anorexia, nausea, vomiting, visual changes, and cardiac arrhythmias.
Contraindications include acute myocardial infarction, ventricular fibrillation, Wolff-Parkinson-White syndrome, myocarditis, hypokalemia, and hypomagnesemia.
Table 19.18 is a drug prototype table for cardiac glycosides featuring maintenance dosing for digoxin. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
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Drug Class Cardiac glycoside Mechanism of Action Blocks the sodium-potassium ATPase pump, which ultimately causes potassium to remain in the cardiac myocyte longer, leading to a stronger force of contraction Increases parasympathetic stimulation of the heart (mechanism unclear), which decreases heart rate |
Drug Dosage Heart failure maintenance dosing: 0.125–0.5 mg orally once daily. |
| Indications Continued heart failure symptoms even though first-line medications for heart failure have been optimized Therapeutic Effects Increases force of contraction Lowers heart rate |
Drug Interactions Quinidine Calcium channel blockers Nonsteroidal anti-inflammatory drugs Amiodarone Beta blockers Diuretics (may affect potassium levels, which may potentiate the effectiveness of digoxin) Food Interactions Foods high in potassium |
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Adverse Effects Fatal cardiac arrhythmias Sinus bradycardia Sinoatrial block Visual disturbances (yellow or green halo around lights) Atrial tachycardia Rash |
Contraindications Acute myocardial infarction Wolff–Parkinson–White syndrome Ventricular fibrillation Hypokalemia Hypomagnesemia |
Safety Alert
Cardiac Glycosides
Cardiac glycosides can cause fetal death in the second trimester. Clients of childbearing age should not become pregnant while taking cardiac glycosides.
Digoxin has a high potential for toxicity with life-threatening consequences.
Nursing Implications
The nurse should do the following for clients who are taking digoxin:
- Assess pulse for 1 minute prior to administering digoxin. If heart rate is less than 60 beats per minute, do not administer the dose.
- Monitor serum digoxin levels and for signs and symptoms of digoxin toxicity. Also monitor serum potassium levels.
- Assess and monitor for adverse effects, drug and food interactions, and contraindications.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking digoxin should:
- Monitor their pulse prior to taking digoxin and contact their health care provider if their pulse is <60 beats per minute.
- Monitor for signs of digoxin toxicity (anorexia, nausea, vomiting, green/yellow halos around lights). They should contact their health care provider immediately if they experience these symptoms.
- Notify their health care provider about symptoms such as dizziness, lightheadedness, or fainting because these could be related to low blood pressure.
Ivabradine
Ivabradine (Corlanor) was introduced fairly recently as an adjunct therapy for clients who are optimized on first-line heart failure medications but still have a reduced ejection fraction and/or symptoms.
Ivabradine is an If current inhibitor that affects the cardiac pacemaker current (If) directly, causing a decreased heart rate and longer diastole. A decreased heart rate lowers the heart’s demand for oxygen, and longer diastole allows for increased oxygenation of cardiac myocytes.
Adverse Effects and Contraindications
Adverse effects include bradycardia, atrial fibrillation, elevated blood pressure, heart block, prolonged QT segment, torsade de pointes, and luminous phenomena (enhanced brightness of light or halo around light). Fetal toxicity has occurred in animal studies.
Contraindications include acute decompensated heart failure, hypotension, history of conduction problems (such as sick sinus syndrome), bradycardia, and liver dysfunction. Ivabradine has been shown to cause fetal toxicity in animal studies; therefore, clients should not be pregnant or become pregnant while taking ivabradine.
Table 19.19 is a drug prototype table featuring ivabradine. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
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Drug Class If current inhibitor Mechanism of Action Blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel that regulates cardiac pacemaker current |
Drug Dosage Heart failure: 5–7.5 mg orally twice daily; maximum dose: 7.5 mg orally twice daily. |
| Indications Stable heart failure with an ejection fraction ≤35% to reduce the risk of hospital admission for worsening heart failure Therapeutic Effects Slows heart rate Allows for longer period of diastole Increases oxygenation of cardiac myocytes |
Drug Interactions Metabolized by CYP450 enzymes/verapamil Diltiazem Food Interactions Grapefruit juice |
| Adverse Effects Bradycardia Atrial fibrillation Elevated blood pressure Heart block Prolonged QT segment Torsade de pointes Luminous phenomena (enhanced brightness of light or halo around light) Fetal toxicity |
Contraindications Acute decompensated heart failure Hypotension History of conduction problems (e.g., sick sinus syndrome, etc.) Bradycardia Liver dysfunction Pregnancy |
Safety Alert
Ivabradine
Clients of childbearing age should take measures not to become pregnant while taking ivabradine due to teratogenic effects (causing harm to embryo or fetus).
Nursing Implications
The nurse should do the following for clients who are taking ivabradine:
- Tell clients to report dizziness or shortness of breath because those may be related to bradycardia and/or atrial fibrillation.
- Inform clients that ivabradine must be taken with food.
- Teach clients about food and drug interactions.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking ivabradine should:
- Report feeling dizzy, lightheaded, or an erratic heartbeat to the health care provider.
- Avoid grapefruit juice.
- Notify the health care provider if pregnant, planning on getting pregnant, or breastfeeding prior to starting ivabradine.