Drugs impacting the renin-angiotensin-Aldosterone system

ARBs interventions

In patients being treated for hypertension, monitor for reduced BP. For patients with heart failure, monitor for a decrease in symptoms such as dyspnea, jugular vein distention, peripheral edema, and cyanosis. Patients with diabetic nephropathy should be monitored for proteinuria and changes in the glomerular filtration rate.

ARBs valsartan treatment of heart failure dosage

PO 40 mg twice per day, up to 160 mg twice per day

ARBs valsartan treatment of hypertension dosage

PO 80 or 160 mg/day alone or in conjunction with other antihypertensive

Similar to ACE inhibitors, ARBs can increase the risk for

hyperkalemia especially when taken with potassium supplements. Although this risk is lower than with ACE inhibitors, patients taking ARBs should have serum potassium levels monitored regularly. Some patients taking ARBs still may need potassium supplements if they are at risk for hypokalemia

ACE inhibitor medications are available as

single-drug formulations, or in formulations that combine an ACE inhibitor with the diuretic hydrochlorothiazide or with a calcium channel blocker.

A patient who is prescribed lisinopril asks the nurse, "Will this drug help the swelling in my legs?" Which nursing response is appropriate?

"Lisinopril may help the edema from progressing, as this drug suppresses aldosterone, which promotes sodium and water excretion."

A 25-year-old female patient is being discharged from the hospital on valsartan after a hypertensive crisis. Which information would the nurse include in the discharge teaching?

"Use contraceptives while taking valsartan." "Take your blood pressure at home to evaluate effectiveness of the medication." "Be sure to change positions slowly, especially when you get up in the morning."

The nurse is providing education to a patient who is being discharged on valsartan. Which patient responses indicate that more education is required?

"Which one of those medications is for my blood pressure? "I have to take it with food or it won't work." "I take it only when my blood pressure is over 180/80 mm Hg."

Drugs classified as ACE inhibitors may be recognized by noting the suffix

-pril, which is found in the generic names of ACE inhibitors such as lisinopril, captopril, benazepril, and enalapril. Lisinopril will be used as a prototypeof the ACE inhibitor class of drugs, and comments about specific other medications within the drug class will be included.

The nurse is administering valsartan to a patient with hypertension at 0800. Based on the onset of the drug, at which time will the nurse anticipate an effect on the patient's blood pressure?

1000

The nurse administered a dose of lisinopril at 0800, and the patient's blood pressure was 189/96 mm Hg. Based on the pharmacodynamics of the drug, at which time would the nurse anticipate the greatest reduction in blood pressure?

1400

For which patients is the use of an angiotensin-converting enzyme (ACE) inhibitor contraindicated?

32-year-old female patient who is 4 months pregnant 62-year-old male patient with a history of renal artery stenosis 29-year-old female patient with a potassium level of 5.2 mEq/L

Mechanism of Action ACE

ACE inhibitors block the enzyme that converts angiotensin I to the vasoconstrictor angiotensin II. This action also reduces the adrenal release of aldosterone, decreasing sodium and water retention by the kidneys while sparing potassium from excretion.

Drug Interactions with ACE Inhibitors: lithium

ACE inhibitors promote sodium and water excretion by the kidneys, which may cause excessive lithium levels in patients on lithium therapy. Serum lithium levels need to be monitored frequently to detect possible lithium toxicity.

The nurse is teaching a course on the mechanism of action of angiotensin-converting enzyme (ACE) inhibitors. Which teaching will the nurse include?

ACE inhibitors suppress conversion of angiotensin I to angiotensin II

Adverse effects of ARBs include: Angioedema

ARBs can cause angioedema, although this is less common with ARBs than ACE inhibitors. Patients who develop angioedema when taking ARBs should stop taking them immediately and should not use them again. Patients who develop angioedema should be given epinephrine subcutaneously.

The nurse is teaching a class on angiotensin receptor blockers (ARBs). What would the nurse include in the teaching?

ARBs lower blood pressure by preventing vasoconstriction. ARBs prevent angiotensin II from stimulating the release of aldosterone ARBs can prevent angiotensin II from inducing structural changes to the heart. ARBs are generally well absorbed. Valsartan crosses the placenta and can cause fetal death.

Mechanism of Action ARBs

ARBs work by blocking angiotensin II from connecting to its receptors in the blood vessels. Unlike ACE inhibitors, which inhibit the production of angiotensin II, ARBs block the action of angiotensin II.

ACE Inhibitors cautions

All ACE inhibitors except lisinopril must be used with caution in patients with liver failure. Lisinopril does not require liver metabolism to exert its actions.

Pharmacokinetics ACE

All ACE inhibitors, except lisinopril and captopril, convert to their active forms in the small intestine and liver. Lisinopril is active as given. All are excreted through the kidneys. Doses must be reduced in patients with kidney disease.

ARBs dosing

All ARBs are PO formulations and can be given without regard to food. Dosages vary according to individual drug. Information for valsartan is provided below.

Before beginning therapy with ARBs, patients should be given the following information:

All of the ARBs are given orally, and you may take them with or without food, although they are often better tolerated with food. If you are a woman of childbearing age you should not take ARBs while pregnant. ARBs have a high risk for fetal injury during the second and third trimesters of pregnancy and a lower risk in the first trimester. If you become pregnant while taking an ARB you should notify the health care provider immediately so that the ARB can be withdrawn immediately. If you experience edema of the tongue or throat you should seek immediate medical attention. These are symptoms of angioedema, which is a potentially fatal reaction to ARBs. Do not alter the dose of or discontinue an ARB without consulting the health care provider. Report shortness of breath, dizziness, and unusual fatigue immediately. Follow a regimen of self-monitoring BP at scheduled intervals.

Identify High-Risk Patients for ARBs

Although ARBs have a lower incidence of causing angioedema, patients with a previous history of angioedema with ACE inhibitors should not be given ARBs unless the benefits outweigh this risk. ARBs are not recommended for use during pregnancy. Patients who have renal artery stenosis release large amounts of renin, which leads to high levels of angiotensin II. This causes BP elevation and constriction of efferent glomerular arterioles, which helps maintain an adequate glomerular filtration rate. Drugs that interfere with angiotensin production or release compromise this, potentially causing chronic kidney disease. ARBs are used with extreme caution in patients with this condition.

Pharmacodynamic Profile of Lisinopril ACE

Although all ACE inhibitors work in a similar manner, the pharmacodynamics can vary by drug. Pharmacodynamics specific to lisinopril include: Onset: 1 hr Peak: 6 to 8 hr Duration: 24 hr Half-life: 12 hr

Pharmacodynamic Profile of Valsartan ARBs

Although all ARBs work in a similar manner, the pharmacodynamics can vary by drug. Pharmacodynamics specific to valsartan include: Onset: Up to 2 hr Peak: 2 to 4 hr Duration: 24 hr Half-life: 6 hr

Adverse Effects of ACE Inhibitors

Angioedema is an extreme allergic reaction where the lips, face, tongue, larynx, and limbs swell. This life-threatening reaction may occur with the first dose or within the first week of ACE inhibitor therapy. African Americans are at higher risk for angioedema. Neutropenia from ACE inhibitor therapy can progress to agranulocytosis. This adverse effect is primarily associated with captopril and is rare. Severe first-dose hypotension may occur in any patient taking an ACE inhibitor for first time. It is most frequently seen in patients with severe hypertension, history of diuretic use, or sodium or blood volume depletion. Treatment includes the nurse assisting the patient to lie down and administering intravenous (IV) saline if necessary. Patients receiving potassium-sparing diuretics, taking potassium supplements, or ingesting potassium-containing salt substitutes are at higher risk for hyperkalemia and tachycardia. Other serious adverse effects include bleeding and chronic kidney disease.

Determine Baseline Data for ARBs

Assess baseline BP and monitor BP throughout therapy with ARBs.

Adverse effects of ARBs include: Fetal harm

Because of known harmful effects to the fetus, ARBs and ACE inhibitors are contraindicated during the second and third trimesters. Because of potential increased risks during the first trimester, both classes of drugs should be discontinued as soon as a woman becomes pregnant.

Nursing interventions for patients taking ACE inhibitors or ARBs include evaluating the effectiveness of ACE inhibitor therapy or ARB therapy and monitoring for potential side effects.

Check BP to determine the drug's effectiveness in decreasing BP to the patient's goal level. Monitor patients closely for early detection of possible dramatic first-dose hypotension. Check BP periodically following initial administration. Monitor for reduction of heart failure symptoms such as shortness of breath, edema, and jugular vein distention. Monitor for neutropenia by obtaining baseline serum WBCs with differential before therapy begins and retaking measurements every 2 weeks for the first 3 months after the first dose. Monitor for symptoms of angioedema.

Drug Interactions with ACE Inhibitors: diuretics and other antihypertensive agents

Diuretics can increase the risk for first-dose hypotension. Diuretics are usually discontinued 2 to 3 days before the patient starts an ACE inhibitor. A diuretic may be added at a later point if BP goals are not reached with ACE inhibitors alone. Using multiple drugs to reduce hypertension may result in a very strong hypotensive effect. When a patient starts an ACE inhibitor, other antihypertensive medication dosages may need to be lowered.

ACE inhibitors doses

Dosages are low initially and then may be gradually increased depending on response. Enalaprilat is the only ACE inhibitor available for parenteral use. All other ACE inhibitors are administered orally. Captopril and moexipril should be taken at least 1 hour before food ingestion. All other ACE inhibitors may be taken with food if desired. Dosages should be decreased in patients with impaired renal function. Starting and maintenance dosages depend on the indication for use.

The nurse is completing discharge teaching, which includes the direction, "Do not stop the angiotensin-converting enzyme (ACE) inhibitor abruptly." Which effect would the nurse tell the patient to expect if the medication were stopped suddenly?

Dramatic increase in blood pressure

ACE Inhibitors interventions

Due to the risk for neutropenia, serum WBCs with differential should be obtained every 2 weeks for the first 3 months after initiating ACE inhibitor therapy and periodically thereafter. Monitor serum potassium levels for early detection of possible hyperkalemia. Closely monitor serum lithium levels in patients receiving lithium therapy. Validate avoidance of NSAIDs, which may impair ACE inhibitors (a drug-drug interaction). Validate avoidance of potassium-containing salt substitutes.

Drug Interactions with ACE Inhibitors: drugs raising potassium levels

Due to their impact on the RAAS, ACE inhibitors spare potassium while promoting sodium and water excretion by the kidneys. Potassium supplements and diuretics that spare potassium, such as spironolactone, are usually discontinued before the patient starts an ACE inhibitor to reduce the risk for hyperkalemia.

Precautions for ACE inhibitors

Inform the health care provider and pharmacist if there is a history of angioedema or other allergies to ACE inhibitors. In addition, inform the health care provider if a history of heart disease, kidney disease, systemic lupus erythematosus, scleroderma, or liver impairment exists. Do not take ACE inhibitors if pregnancy occurs. Women of childbearing age should avoid pregnancy while taking ACE inhibitors due to risk for major fetal harm.

ACE inhibitors reduce BP by the following means:

Inhibiting the enzyme that converts angiotensin I to angiotensin II Suppressing aldosterone from expanding blood volume, which promotes potassium retention and sodium and water excretion ACE inhibitors have minimal effect on cardiac output and heart rate.

Pharmacokinetics ARBS

Most ARBs are well absorbed and extensively metabolized. Valsartan is protein bound and excreted in the urine, feces, and breast milk.

Drug Interactions with ACE Inhibitors: nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs impair the BP-lowering impact of ACE inhibitors and should be avoided. Examples of NSAIDs include aspirin and ibuprofen.

Adverse effects for ACE inhibitors

Notify the health care provider if a nonproductive cough develops, but do not discontinue drug use without medical consultation. If dizziness or lightheadedness occurs, lie down immediately for safety. Angioedema, a severe allergic reaction to lisinopril, can occur up to a week after the first dose. Seek medical intervention immediately if swelling of the lips, face, or throat occurs. Diabetic patients taking insulin or PO hypoglycemic agents may experience lowered blood sugar levels, which can cause hypoglycemic events.

Determine Baseline Data ACE

Obtain baseline BP. Obtain baseline serum white blood cells (WBCs) with differential due to the risk for neutropenia with ACE inhibitors. Without early detection, neutropenia may lead to agranulocytosis, a potentially fatal condition where the body fails to defend against infection. This risk occurs mainly with captopril. Obtain baseline lithium level for patients taking lithium due to the risk for lithium toxicity. Review diet, medication, and over-the-counter drug histories for recent use of diuretics, potassium supplements, and salt substitutes containing potassium because ACE inhibitors can increase potassium levels.

ARBs Cautions

Older patients and those who have renal dysfunction have increased sensitivity to the effects of ARBs. ARBs should be used cautiously in these patients.

ACE inhibitors lisinopril dosage

Oral (PO) 10 mg initially; 10 - 40 mg/day

ACE Inhibitors contraindications

Patients who are pregnant; ACE inhibitors can cause major fetal harm. Patients with a history of angioedema, a medical emergency manifested by swelling of the tongue, lips, pharynx, and eyes. Patients with high serum potassium. Patients with renal artery stenosis.

ARBs contraindications

Patients who are pregnant; ARBs can cause major fetal harm. Patients who have a history of angioedema. Patients with renal failure.

Adverse effects of ARBs include: Chronic kidney disease

Patients with bilateral renal artery stenosis or stenosis in the artery to a single remaining kidney should take ARBs or ACE inhibitors with extreme caution because these drugs can cause chronic kidney disease.

Patients who are at high risk for serious adverse events for ACE include:

Patients with depleted sodium or blood volume Patients with impaired renal function, who may require smaller doses for safety Patients who are taking potassium supplements or who have recently used potassium-sparing diuretics Patients with collagen vascular diseases such as systemic lupus erythematosus and scleroderma Patients who are pregnant, because ACE inhibitors are not recommended for use in pregnancy

A patient who is hospitalized following a planned orthopedic surgery has been taking a routine dose of lisinopril since the operative day. Which action will the nurse take when a sudden onset of facial swelling is noted?

Prepare to administer epinephrine subcutaneously.

The RAAS regulates blood pressure (BP) in the body through vasoconstriction and increases in blood volume. The system includes the following steps.

Renin forms angiotensin I. ACE converts angiotensin I to angiotensin II. Angiotensin II, a potent vasoconstrictor, triggers the adrenal cortex to secrete aldosterone. Aldosterone enhances excretion of potassium and resorption of sodium and water in the kidneys, increasing blood volume.

General teaching for ACE inhibitors

Take the ACE inhibitor at generally the same time every day; this will make it easier to remember to take the drug. All ACE inhibitors may be taken with food except captopril and moexipril, which must be taken at least 1 hour before eating. Avoid using NSAIDs, as they impair the effectiveness of ACE inhibitors at reducing hypertension. Notify the health care provider of any early symptoms of infection as there is a risk for neutropenia, especially with captopril. Frequent blood draws will be needed to monitor for serious side effects. Do not stop taking the medication abruptly. The health care provider needs to coordinate any discontinuation of ACE inhibitor therapy. The initial dose is usually low and is then increased gradually depending on response to treatment. Avoid the use of commonly available salt substitutes, as many contain potassium, and use could increase the risk for excessive serum potassium.

Side Effects and of ACE Inhibitors

The most common side effect of ACE inhibitor therapy is a persistent, irritated cough caused by the accumulation of angiotensin I (bradykinin). The effect is associated with all drugs classified as ACE inhibitors. This "ACE Cough" can be resolved if the health care provider discontinues ACE inhibitor therapy for the patient. Other side effects include nausea, vomiting, headache, dizziness, fatigue, and changes in the taste of food.

The nurse is preparing to administer captopril to a patient. Which patient action would cause the nurse to hold the medication?

The patient is eating breakfast. Food decreases captopril absorption by 35%, so the medication should be taken on an empty stomach. The nurse would hold the medication and administer at least 1 hour after food intake.

What crosses the placenta and can cause fetal death in pregnancy.

Valsartan

Drug Interactions with ARBs

When ARBs are administered with other antihypertensive agents, the antihypertensive effects build up and can cause hypotension. Doses of drugs such as diuretics, sympatholytics, vasodilators, ACE inhibitors, and calcium channel blockers may need to be reduced when ARBs are added to the drug regimen for patients with hypertension.

ARBs

are used to block the effects of angiotensin II on the target tissues. ARBs act to prevent systemic vasoconstriction of arterioles and veins and thereby lower BP. They block angiotensin II-induced renal vasoconstriction to prevent sodium and water retention. ARBs also prevent angiotensin II from stimulating aldosterone release. ARBs can prevent angiotensin II from altering cardiac structure.

ARBs dilate the blood vessels, causing

blood to pool in the lower vessels. Because of this, patients should take caution when rising and changing positions.

Toxic drug effects of ARBs include:

chest pain, hypotension, tachycardia, and bradycardia (if overdose occurs, supportive treatment with IV fluids is indicated)

There are several ARBs on the market; examples include

losartan, valsartan, and irbesartan. Valsartan will be the prototype ARB reviewed in this lesson.

ACE inhibitors lisinopril indication

treatment of hypertension

Side effects of ARBs include:

weakness and fatigue, diarrhea, hypoglycemia, dizziness, urinary tract infection, and anemia