19.2: Drugs Affecting the Renin-Angiotensin-Aldosterone System
By the end of this section, you should be able to:
- 19.2.1 Identify the characteristics of drugs affecting the renin-angiotensin-aldosterone system that are used to treat heart failure.
- 19.2.2 Explain the indications, actions, adverse reactions, and interactions of drugs affecting the renin-angiotensin-aldosterone system that are used to treat heart failure.
- 19.2.3 Describe nursing implications of drugs affecting the renin-angiotensin-aldosterone system that are used to treat heart failure.
- 19.2.4 Explain the client education related to drugs affecting the renin-angiotensin-aldosterone system that are used to treat heart failure.
Angiotensin-Converting (ACE) Enzyme Inhibitors
As mentioned in Antihypertensive and Antianginal Drugs, Angiotensin-converting enzyme (ACE) inhibitors are a classification of drugs that block the body’s production of angiotensin II. Angiotensin II is one of the products of the renin-angiotensin-aldosterone system (RAAS) (see Figure 19.4), and it stimulates multiple end-organ effects. Two of these effects that are important in heart failure are constriction of arterioles and sodium and water retention of the kidneys. Vasoconstriction causes increased afterload, and sodium and water retention cause increased preload. In heart failure, the heart is already struggling to maintain an adequate cardiac output. Both increased afterload and increased preload will make this task more difficult. ACE inhibitors have been shown to decrease morbidity and mortality in clients with heart failure (Heidenreich et al., 2022).
Special Considerations
ACE Inhibitors
Black clients with hypertension demonstrate a lower response to ACE inhibitor monotherapy. ACE inhibitors interfere with the renin-angiotensin-aldosterone system, which causes high blood pressure when renin levels are high. Black clients often have hypertension but also have lower levels of renin. Therefore, concomitant therapy may be required to increase response to antihypertensive therapies.
(Source: Astra Zeneca, 2012)
Adverse Effects and Contraindications
ACE inhibitors are relatively safe to use and have a low incidence of serious adverse effects. Adverse effects include angioedema, non-productive cough, neutropenia (low neutrophils in the blood), agranulocytosis (low granulocytes in the blood), proteinuria (protein in the urine), and rash. Hypotension may develop. Clients may develop an ACE inhibitor–associated cough (a persistent, dry, itchy cough). Hyperkalemia (elevated potassium level in the blood) may develop.
ACE inhibitors cause fetal toxicity and should be immediately discontinued if pregnancy occurs. Clients with renal impairment should use cautiously. Clients with a previous hypersensitivity reaction to an ACE inhibitor should not be prescribed this classification of drug.
Table 19.4 is a drug prototype table for ACE inhibitors featuring lisinopril. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Angiotensin-converting enzyme (ACE) inhibitor Mechanism of Action Inhibits the enzyme that converts angiotensin I to angiotensin II and thereby suppresses the renin-angiotensin-aldosterone system |
Drug Dosage
2.5–40 mg orally twice daily. |
|
Indications
Hypertension Heart failure Reduction of mortality in acute myocardial infarction Therapeutic Effects Lowers blood pressure Increases blood supply and oxygen to the heart |
Drug Interactions
Aliskiren Lithium Sacubitril Food Interactions Alcohol Tobacco |
|
Adverse Effects
Angioedema Hyperkalemia Fatigue Orthostatic hypotension Asthenia Diarrhea Nausea/vomiting Headache Dizziness/vertigo Cough Rash Abdominal pain Angina |
Contraindications
Hypersensitivity History of angioedema Pregnancy (fetal toxicity) Caution: Aortic stenosis Diabetes Syncope Orthostatic hypotension Impaired renal function Breastfeeding |
Nursing Implications
The nurse should do the following for clients who are taking ACE inhibitors:
- Assess the client’s blood pressure and pulse on an ongoing basis with initial dosing and intermittently during drug therapy.
- Assess and monitor the client 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.
Safety Alert
ACE Inhibitors
Taking ACE inhibitors with potassium-containing salt substitutes or consuming large amounts of high-potassium foods increases the risk of hyperkalemia. Having a blood potassium level above 6.0 mmol/L is considered a medical emergency and can result in cardiac arrest.
Clients of childbearing age should take measures not to become pregnant while taking ivabradine due to teratogenic effects (causing harm to embryo or fetus).
Client Teaching Guidelines
The client taking an ACE inhibitor should:
- Avoid foods high in potassium and salt substitutes (because these are high in potassium) due to the aldosterone release.
- Report side effects such as cough, angioedema, or anaphylactic reactions to their health care provider.
- Notify their health care provider if they experience abdominal pain, joint or muscle aches, muscle weakness, change in the amount of urine produced, or trouble breathing.
- Be aware that a persistent cough may develop when taking ACE inhibitors.
- Notify their health care provider if pregnant, planning on getting pregnant, or breastfeeding prior to starting an ACE inhibitor.
- Report symptoms such as chest pain, slurred speech, hemiparesis, and difficulty speaking or walking to their health care provider immediately because these may be symptoms of a heart attack or stroke.
- Notify their health care provider about symptoms such as dizziness, lightheadedness, or fainting because these could be related to low blood pressure.
Angiotensin II Receptor Blockers
Angiotensin II receptor blockers (ARBs) are a classification of drugs that bind to and inhibit angiotensin II type I receptors. ARBs work directly at the receptor site to block angiotensin II from binding with receptors on the cells (see Figure 19.4). The effect of ARBs is similar to that of ACE inhibitors; however, the side effects are lessened. This means that the potential for angioedema is decreased. Also, there is no side effect of cough.
Angiotensin II receptor blockers decrease blood pressure and therefore decrease afterload. This is beneficial in treating heart failure since decreased afterload means the heart does not have to work as hard to generate stroke volume.
Table 19.5 lists common ARBs used in the management of heart failure and typical routes and dosing for adult clients. A comprehensive list of ARBs can be found in Antihypertensive and Antianginal Drugs.
| Drug | Routes and Dosage Ranges |
|---|---|
|
Candesartan
( Atacand ) |
4 mg orally daily; maximum dose: 32 mg daily. |
|
Losartan
( Cozaar ) |
25–150 orally mg daily. |
|
Valsartan
( Diovan ) |
20–160 orally mg daily. |
Adverse Effects and Contraindications
Adverse effects of ARBs include dizziness, muscle cramps, weakness, heartburn, diarrhea, leg swelling, headaches, and weight loss. Serious adverse effects include angioedema, hypotension, hepatic impairment, and hyperkalemia.
ARBs cause fetal toxicity and should not be taken during pregnancy. Clients with hepatic impairment should use ARBs cautiously. Clients with a previous hypersensitivity reaction or angioedema to an ARB inhibitor should not be prescribed this classification of drug. Clients with a history of mood disturbances or who are at risk for mood disturbances should be monitored closely for suicidal ideation.
Table 19.6 is a drug prototype table for ARBs featuring losartan. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Angiotensin II receptor blocker (ARB) Mechanism of Action Blocks the binding of angiotensin II to the angiotensin I receptor, thereby decreasing vasoconstriction and lowering blood pressure |
Drug Dosage
25–150 mg orally daily. |
|
Indications
Hypertension Heart failure Nephropathy in clients with type 2 diabetes Therapeutic Effects Lowers blood pressure Increases blood supply and oxygen to the heart |
Drug Interactions
Aliskiren Lithium Potassium-sparing diuretics (may increase hyperkalemia) Food Interactions Alcohol Tobacco |
|
Adverse Effects
Hyperkalemia Dizziness Syncope Increased thirst Decreased urinary output Irregular heartbeat Angioedema |
Contraindications
Hypersensitivity Pregnancy (fetal toxicity) Caution: Hepatic impairment Renal impairment Hypotension Hypovolemia Hyperkalemia |
Special Considerations
ARBs
The RAAS has been associated with increased risk of mood disorders. The use of ARBs may be associated with an increased risk of suicide compared with other antihypertensive therapies.
Black clients with hypertension demonstrate a lower response to ARB monotherapy. Concomitant therapy may be required to increase response to antihypertensive therapies.
Older adults and clients with hepatic impairment should start on a low initial dose because the drug is metabolized by the liver.
(Source: Colvin et al., 2020)
Nursing Implications
The nurse should do the following for clients who are taking ARBs:
- Monitor the client’s blood pressure as prescribed.
- Monitor the client for interactions because many medications and herbal supplements interact with ARBs.
- Monitor the client for adverse effects, including electrolyte imbalances and alterations in liver and renal function.
- 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 an ARB should:
- Avoid foods high in potassium and salt substitutes (because these substitute potassium for sodium) due to the aldosterone release.
- Report side effects such as cough, angioedema, or anaphylactic reactions to the health care provider.
- Notify their health care provider if they experience abdominal pain, joint or muscle aches, muscle weakness, change in the amount of urine produced, or trouble breathing.
- Notify their health care provider if pregnant, planning on getting pregnant, or breastfeeding prior to starting an ARB.
- Notify their health care provider about symptoms such as dizziness, lightheadedness, or fainting because these could be related to low blood pressure.
Angiotensin Receptor/Neprilysin Inhibitors
Recently, a new classification of heart failure medication was developed, angiotensin receptor/neprilysin inhibitors (ARNIs) . This combination medication is a first-line medication for many classifications of heart failure. It is a combination of an ARB and a new type of medication, a neprilysin inhibitor. There currently is only one medication in the ARNI class: sacubitril/valsartan ( Entresto ).
In heart failure with reduced ejection fraction, there is a lot of stress on the left ventricle as well as left ventricular dilation. This is due to an increased preload. When the ventricle dilates to a point that is no longer helpful to the heart, the myocytes release brain natriuretic peptide (BNP). BNP stimulates a compensatory mechanism that leads to vasodilation and decreased sodium and water absorption. Vasodilation and diuresis decrease afterload and preload, which makes the workload of the heart decrease.
Neprilysin is an enzyme that breaks down BNP. The inhibition of neprilysin means that BNP can stay in the body’s circulatory system longer. If BNP stays in the system longer, then vasodilation and decreased sodium and water reabsorption will last longer, which will decrease afterload and preload. This will decrease the workload of the heart.
Adverse Effects and Contraindications
Adverse effects of ARNIs include angioedema, hypotension, renal impairment, and hyperkalemia.
ARNIs contain ARBs and cause fetal toxicity; they should not be taken during pregnancy. Clients with hepatic impairment should use ARNIs cautiously. Clients with a previous hypersensitivity or angioedema reaction to an ARB inhibitor should not be prescribed this classification of drug. Clients with a history of mood disturbances or who are at risk for mood disturbances should be monitored closely for suicidal ideation.
Clinical Tip
Reviewing Medications
It is important for the nurse to review all of a client’s medications. Clients should not take ACE inhibitors, ARBs, or ARNIs at the same time. Clients should be prescribed only one of these classifications of medication at a time.
Table 19.7 is a drug prototype table for angiotensin receptor/neprilysin inhibitors featuring sacubitril/valsartan. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Angiotensin receptor/neprilysin inhibitor Mechanism of Action Causes angiotensin receptor blockade and inhibition of the enzyme that breaks down BNP |
Drug Dosage
Initial dose: 49 mg/51 mg orally twice daily; maximum dose: 97 mg/103 mg twice daily. |
|
Indications
Heart failure Therapeutic Effects Vasodilation |
Drug Interactions
Potassium-sparing diuretics (may lead to increased serum potassium) Nonsteroidal anti-inflammatory drugs (NSAIDs; may lead to increased risk of renal impairment) Lithium (increased risk of lithium toxicity) ACE inhibitors (increased risk of angioedema) Food Interactions No significant interactions |
|
Adverse Effects
Angioedema Hypotension Hyperkalemia Cough Dizziness Renal failure |
Contraindications
Pregnancy (fetal toxicity) History of angioedema with ACE inhibitor or ARB therapy |
Nursing Implications
The nurse should do the following for clients who are taking ARNIs:
- Monitor the client’s blood pressure as prescribed.
- Monitor the client for medication and herbal supplement interactions.
- Report adverse effects, including electrolyte imbalances and alterations in liver and renal function, to the health care provider.
- 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 an ARNI should:
- Avoid foods high in potassium and salt substitutes (because these are high in potassium) due to the aldosterone release.
- Report side effects such as cough, angioedema, and anaphylactic reactions to the health care provider.
- Notify their health care provider if they experience abdominal pain, joint or muscle aches, muscle weakness, change in the amount of urine produced, or trouble breathing.
- Notify their health care provider if pregnant, planning on getting pregnant, or breastfeeding prior to starting an ARNI.
- Notify their health care provider about symptoms such as dizziness, lightheadedness, or fainting because these could be related to low blood pressure.
Mineralocorticoid Receptor Antagonists
Mineralocorticoid receptor antagonists (MRAs) (also known as aldosterone antagonists ) are often categorized as diuretics because they ultimately do cause diuresis. When the RAAS is activated, one of the end results is the stimulation of the adrenal glands to secrete aldosterone. (See Figure 19.4 earlier in the chapter.) Aldosterone binds to receptors on cells in the distal tubule of the nephron, which then causes them to reabsorb sodium and water. During this process, potassium secretion increases. Aldosterone antagonists block the receptor so that aldosterone can’t bind there. The end result is increased sodium and water excretion into the urine, and potassium reabsorption. Aldosterone antagonists are referred to as potassium-sparing diuretics .
MRA medications have been found to reduce the risk of all-cause mortality in clients with heart failure (Heidenreich et al., 2022).
Table 19.8 lists the two MRAs used in heart failure and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
|
Spironolactone
( Aldactone ) |
12.5–25 mg orally daily; maximum dose: 50 mg daily. |
|
Eplerenone
( Inspra ) |
25–50 mg orally daily. |
Adverse Effects and Contraindications
Adverse effects of MRAs include hyperkalemia, hypotension, worsening renal failure, electrolyte abnormalities, and gynecomastia (breast enlargement and/or sensitivity).
MRAs should not be taken during pregnancy. Because MRAs cause potassium retention, they should not be used by clients who have kidney disease. MRAs must be used carefully with other medications, such as ACE inhibitors and ARBs, that may cause hyperkalemia.
Table 19.9 is a drug prototype table for MRAs featuring spironolactone. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Mineralocorticoid receptor antagonist (MRA) Mechanism of Action Binds to receptors in the nephron so that aldosterone is not able to bind, which leads to increased diuresis |
Drug Dosage
12.5–25 mg orally daily; maximum dose: 50 mg daily. |
|
Indications
Heart failure Hypertension Edema associated with hepatic cirrhosis or nephrotic syndrome Therapeutic Effects Diuresis |
Drug Interactions
Agents that increase serum potassium Lithium (increased risk for lithium toxicity) NSAIDs Digoxin Aspirin (may reduce the efficacy of spironolactone) Food Interactions No significant interactions |
|
Adverse Effects
Hyperkalemia Hypotension Worsening renal failure Electrolyte abnormalities Gynecomastia |
Contraindications
Hyperkalemia Addison’s disease Pregnancy Concomitant use of eplerenone |
Safety Alert
MRAs
MRAs can cause significant hyperkalemia. The client should have their serum electrolytes monitored regularly while taking MRAs. If hyperkalemia occurs, the drug may have to be discontinued.
Nursing Implications
The nurse should do the following for clients who are taking MRAs:
- Monitor the client for medication and/or food interactions.
- Monitor the client for adverse effects, including electrolyte imbalances and alteration renal function.
- 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 an MRA should:
- Avoid foods high in potassium and salt substitutes (because these are high in potassium) due to the aldosterone release.
- Notify their provider if they are taking an ACE inhibitor, ARB, or other potassium-sparing drugs.
- Notify their health care provider if pregnant, planning on getting pregnant, or breastfeeding prior to starting an MRA.
- Notify their health care provider about breast enlargement and/or tenderness.
- Notify their health care provider about symptoms such as dizziness, lightheadedness, or fainting because these could be related to low blood pressure.
FDA Black Box Warning
Drugs Affecting the Renin-Angiotensin-Aldosterone System
Fetal toxicity can occur when taking ACE inhibitors during the second and third trimesters of pregnancy or when taking ARBs or ARNIs during pregnancy.