Functions of RAAS
1.Regulation of blood pressure, blood volume, and fluid and electrolyte balance
2.Mediates pathophysiologic changes associated with hypertension, heart failure, and myocardial infarction
Formation of Angiotensin II by Renin and Angiotensin-Converting Enzyme (ACE) (Fig 44-1)
1.Renin�Catalyzes formation of angiotensin I from angiotensinogen, which is rate-limiting step of angiotensin II formation
2.Regulation of renin release�Increase due to decrease in BP, blood volume, plasma sodium content, or renal perfusion pressure; decr
Action of Angiotensin II
1. Vasoconstriction�Extremely potent vasoconstrictor; acts directly on vascular smooth muscle especially in arterioles and less in veins, by action in the CNS to increase sympathetic outflow, by increasing release of NE from neurons and by acting on adren
Classes of medication inhibit RAAS function
1. ACE inhibitors
2. Angiotensin receptor blockers
3. Aldosterone antagonists
4. Direct renin inhibitors
5. Beta-blockers
Enalapril (Vasotec) Medication Class
Angiotensin Converting Enzyme Inhibitor; ACE inhibitor
Enalapril (Vasotec) Mechanism of Action
-Inhibit the action of the enzyme ACE resulting in decreased production of angiotensin II (and therefore decreased release of aldosterone). The same enzyme also causes the breakdown of the vasodilator bradykinin. So ACE inhibitors also cause an increase i
Enalapril (Vasotec) Therapeutic Uses
-Enalapril itself is approved for hypertension, heart failure, and asymptomatic left ventricular dysfunction
1.Hypertension
a.Decreases angiotensin II which results in vasodilation
b.Increases bradykinin which results in vasodilation
c.Decreases aldostero
Enalapril (Vasotec) Adverse Effects
1.First-dose hypotension - from vasodilation
2.Cough - Persistent, dry, nonproductive, irritating cough; related to increase in bradykinin
3.Hyperkalemia - Decreased aldosterone action causes potassium retention by kidney
4.Fetal injury - Contraindicated
Enalapril (Vasotec) Precautions, Warnings, and Contraindications
1.Contraindicated during pregnancy.
2.Contraindicated in patients with bilateral renal artery stenosis or stenosis to a single remaining kidney.
3.Contraindicated if patient has had a previous reaction (angioedema) to an ACE inhibitor.
-Use caution in pat
Enalapril (Vasotec) Drug Interactions
Diuretics, antihypertensive agents, drugs that raise potassium levels, lithium, NSAIDs
Enalapril (Vasotec) Pharmacokinetics
Prodrug. Undergoes renal excretion.
Enalapril (Vasotec) Nursing Implications
1.Preadministration Assessment: BP, renal function, volume status, pregnancy status, potassium. Identify patients in which ACE inhibitors would be contraindicated including history of angioedema from ACE inhibitor or bilateral renal artery stenosis. Check
Other drugs that are similar to prototype Enalapril (Vasotec)
1.Benazepril (Lotensin)
2.Captopril (Capoten) - Take at least one hour before meals. Can also cause adverse effects of dysgeusia, rash, and neutropenia.
3.Fosinopril (Monopril)
4.Lisinopril (Prinivil, Zestril)
5.Moexipril (Univasc) - Take at least one hou
Losartan (Cozaar) Medication Class
Angiotensin II Receptor Blocker (ARB)
Losartan (Cozaar) MOA
Blocks action of angiotensin II at receptors in blood vessels, adrenals and all other tissues; does not inhibit kinase II so no increase in bradykinin
Losartan (Cozaar) Uses
-List is for class of ARBs. Losartan itself is approved for use in hypertension, stroke prevention, and diabetic nephropathy.
1. Hypertension - through block of angiotensin II actions; note that there is no increase in vasodilatory bradykinin here though
Losartan (Cozaar) Adverse Effects
1. ARBs do not cause cough because there is no increase in bradykinin.
2. Hyperkalemia
3. Angioedema
4. Fetal harm
5. Renal failure
Losartan (Cozaar) Precautions, Warnings, and Contraindications
1. Contraindicated during pregnancy.
2. Contraindicated in patients with bilateral renal artery stenosis or stenosis to a single remaining kidney.
3. Contraindicated if patients has had a previous reaction (angioedema) to an ARB.
-Use caution in patients
Losartan (Cozaar) Drug Interactions
Diuretics, antihypertensive agents, drugs that raise potassium levels, lithium, NSAIDs
Losartan (Cozaar) Pharmacokinetics
metabolized to active metabolite.
Losartan (Cozaar) Nursing Implications
1.Preadministration Assessment: BP, renal function, potassium, volume status, pregnancy status. Watch for patients in which an ARB would be contraindicated. Check for drug interactions.
2.Administration: Oral
3.Monitoring: BP, renal function, potassium
Other drugs that are similar to prototype Losartan (Cozaar)
1. Candesartan (Atacand)
2. Eprosartan (Teveten)
3. Irbesartan (Avapro)
4. Olmesartan (Benicar)
5. Telmisartan (Micardis)
6. Valsartan (Diovan)
7. Azilsartan (Edarbi)
Eplerenone (Inspra) Medication Class
Aldosterone antagonist
Eplerenone (Inspra) Mechanism of Action
Blocks action of aldosterone in kidney as well as nonrenal sites
Eplerenone (Inspra) Therapeutic Uses
Hypertension and heart failure
Eplerenone (Inspra) Adverse Effects
Hyperkalemia
Eplerenone (Inspra) Precautions, Warnings, and Contraindications
Contraindicated in patients with hyperkalemia, impaired renal function, type 2 diabetes with microalbuminuria.
Eplerenone (Inspra) Drug Interactions
Inhibitors of CYP3A4, drugs that raise potassium levels, potassium supplements, salt substitutes, lithium
Eplerenone (Inspra) Pharmacokinetics
Metabolized by CYP3A4
Eplerenone (Inspra) Nursing Implications
1.Preadministration Assessment: Potassium, renal function. Watch for contraindications and drug interactions.
2.Administration: Oral
3.Monitoring: Potassium, renal function
Other drugs that are similar to prototype Eplerenone (Inspra)
1. Spironolactone (Aldactone) - Also potassium sparing diuretic (Chapter 41)
Aliskiren (Tekturna) Medication Class
Direct renin inhibitor
Aliskiren (Tekturna) Mechanism of Action
Inhibits the conversion of angiotensinogen to angiotensin I by renin
Aliskiren (Tekturna) Therapeutic Uses
Hypertension
Aliskiren (Tekturna)
Angioedemia, hyperkalemia, fetal injury, GI effects
Aliskiren (Tekturna) Precautions, Warnings, and Contraindications
Do not use during pregnancy. Watch renal function and potassium. Do not use in combination with ACE inhibitors or ARBs in diabetic patients.
Aliskiren (Tekturna) Drug Interactions
Drugs that raise potassium levels, antihypertensive agents
Aliskiren (Tekturna) Pharmacokinetics
Eliminated by hepatic metabolism and urinary excretion.
Aliskiren (Tekturna) Nursing Implications
1.Preadministration Assessment: BP, potassium, renal function
2.Administration: Oral
3.Monitoring: BP, potassium renal function