ANGIOTENSIN-CONVERTING ENZYME INHIBITORS Dana Bartlett, RN, BSN, MSN, MA, CSPI Dana Bartlett is a professional nurse and author. His clinical experience includes 16 years of ICU and ER experience and over 20 years of as a poison control center information specialist. Dana has published numerous CE and journal articles, written NCLEX material, written textbook chapters, and done editing and reviewing for publishers such as Elsevier, Lippincott, and Thieme. He has written widely on the subject of toxicology and was a contributing editor, toxicology section, for Critical Care Nurse journal. He is currently employed at the Rocky Mountain Poison Control Center. ABSTRACT The class of angiotensin converting enzyme (ACE) inhibitors are widely prescribed for conditions of primary hypertension. Hypertension is a very common disease that affects approximately 75 million Americans or roughly 1 in 3 adults. ACE inhibitors also have distinct, specific advantages for treating hypertensive patients who have chronic kidney disease, diabetes mellitus, heart failure, and myocardial infarction. They are known to prevent mortality related to a cardiovascular event. Except for captopril and lisinopril, the ACE inhibitors are pro-drugs, changed in the liver to a pharmacologically active metabolite. ACE inhibitors may differ in their pharmacokinetic properties, such as peak blood levels and effect on blood pressure depending on the drug. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1 Policy Statement This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities. Continuing Education Credit Designation This educational activity is credited for 2.5 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity. Pharmacology content is 2.5 hours. Statement of Learning Need It is important for health clinicians to have current information about ACE inhibitors, specifically, the pharmacological profile, therapeutic uses, adverse effects, contraindications, warnings, and for the treatment of certain disease states. Additionally, patient monitoring during therapy with an ACE inhibitor, and how to manage ACE inhibitor-induced angioedema and ACE inhibitor overdose will impact patient care outcomes. Course Purpose To increase health clinician knowledge of the recommended use, benefits and risks of ACE Inhibitor medication use. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 2 Target Audience Advanced Practice Registered Nurses and Registered Nurses (Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion) Course Author & Planning Team Conflict of Interest Disclosures Dana Bartlett, RN, BSN, MSN, MA, CSPI, William S. Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC All have no disclosures Acknowledgement of Commercial Support There is no commercial support for this course. Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article. Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3 1. The renin-angiotensin system (RAS) regulates blood pressure by, among other things, a. causing the kidneys to convert pre-renin to renin. b. synthesizing renin to angiotensin I in the kidneys. c. increasing renal blood flow. d. increasing serum sodium. 2. _______________ binds to specific receptors, and it increases blood pressure by its action as a potent vasoconstrictor. a. Angiotensin I b. Renin c. Angiotensin II d. Sodium 3. The angiotensin converting enzyme (ACE) inhibitors have the net effect of a. decreasing the activity of renin. b. lowering blood pressure. c. increasing the vasoconstrictive action of angiotensin II. d. increasing serum sodium levels in the body. 4. True or False: The ACE inhibitors and the angiotensin receptors blockers (ARBs) both lower blood pressure by their effects on the RAS using the same methods. a. True b. False 5. Treatment of __________________ is a primary use of ACE inhibitors. a. hypotension b. aortic stenosis c. cholestatic jaundice d. cardiovascular diseases nursece4less.com nursece4less.com nursece4less.com nursece4less.com 4 Introduction The angiotensin converting enzyme inhibitors are one of the most widely used antihypertensive medications, and they are a first-line choice for treating primary hypertension according to the Eighth Joint National Committee guideline for the management of high blood pressure in the general non-black population and in patients 18 years or older who have chronic kidney disease. The angiotensin converting enzyme inhibitors are also often used to treat hypertension associated with specific clinical conditions, diabetic nephropathy, and their use is considered standard care for patients who have recently had an ST segment elevation myocardial infarction. ACE Inhibitors And The Renin-Angiotensin System The antihypertensive effect of the angiotensin-converting enzyme (ACE) inhibitors is mediated through the renin-angiotensin system (RAS), one of many homeostatic mechanisms the body uses to regulate blood pressure. The RAS also regulates fluid, potassium, and sodium balances. The RAS is very complex, and it has other physiological effects aside from blood pressure control, but this discussion will focus on the RAS and hypertension. The effect of the RAS on blood pressure is complex, but the basic process is highlighted below. • Decreased renal blood flow, volume depletion, decrease in serum sodium, and sympathetic stimulation cause the kidneys to convert pre- renin to renin. Renin is an enzyme that converts angiotensinogen, a compound that is synthesized by the liver, to angiotensin I. • Angiotensin I (no direct biological actions and a precursor) is then changed to angiotensin II by ACE. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5 • Angiotensin II binds to specific receptors, and it increases blood pressure by its action as a potent vasoconstrictor, increasing the secretion of the hormone aldosterone, and aldosterone increases renal tubular reabsorption of sodium and water, and stimulating the sympathetic nervous system. The net result is an increase in blood pressure, and the RAS is the primary way long-term control of blood pressure is attained. The ACE inhibitors inhibit the activity of ACE. This decreases the production of angiotensin II, increases the activity of renin, and decreases the secretion of aldosterone. The net effect is a lowered blood pressure. The RAS can also be manipulated to lower blood pressure by preventing angiotensin II from binding to the angiotensin I and angiotensin II receptors. These are G protein-coupled receptor for which angiotensin II is a ligand, and the angiotensin receptors blockers (ARBs) like valsartan prevent ligand binding to the receptor and thus diminish the vasoconstrictive action of angiotensin II. The ACE inhibitors and the ARBs both lower blood pressure by their effects on the RAS by but different methods. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6 Pharmacological Profile Of Ace Inhibitors Angiotensin-converting enzyme inhibitors are available as tablets and a solution for injection. ACE inhibitors are also available combined with a thiazide diuretic or with a calcium channel blocker. The ACE inhibitors currently available in the United States are listed in Table 1. The generic name is followed by the trade name. Table 1: ACE Inhibitors Benazepril (Lotensin) Captopril (Capoten) Enalapril (Vasotec) Fosinopril (Monopril) Lisinopril (Prinivil, Zestril) Moexipril (Univasc) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril Mavik) Pharmacological Category Angiotensin-Converting Enzyme (ACE) Inhibitor, antihypertensive. Uses There are slight differences in the prescribing information for the ACE inhibitors, but they are not significant. The four primary uses for ACE inhibitors are: 1) Treatment of hypertension, 2) Treatment of heart failure, symptomatic, reduced ejection fraction, 3) Improving left ventricular function and decreasing mortality after acute myocardial infarction, and 4) Treatment of diabetic nephropathy. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7 US Boxed Warning Drugs that act on the RAS can cause injury, fetal toxicity, and death to a developing fetus. Discontinue an ACE inhibitor as soon as it is known the patient is pregnant. Contraindications The potential for allergic cross-reactivity between ACE inhibitors is unclear, so administration of one ACE inhibitor to patient who has had an allergic reaction to another is inadvisable. Patients With Diabetes Mellitus and Taking Renin Inhibitor Aliskiren The concomitant use of an ACE inhibitor and aliskiren in patients who have diabetes mellitus is contraindicated. Aliskiren itself has the potential to cause hyperkalemia, hypotension, and renal impairment, this risk is increased if the patient is given an ACE inhibitor,1,2 and hypotension, hyperkalemia, and renal impairment are potential adverse effects