Angiotensin II Receptor Blockers (ARB, ARb)


Article Author:
Robert Hill


Article Editor:
Prabhakar Vaidya


Editors In Chief:
Wanda Wright
Cynthia Oster


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
9/27/2019 10:39:28 AM

Indications

The renin-angiotensin-aldosterone system (RAAS) is intricately involved in the pathophysiology of several diseases including hypertension, congestive heart failure, and chronic kidney disease of all types including diabetic nephropathy. Pharmaceutical RAAS blockade has is a common and successful strategy in each of these conditions.[1][2][3] 

Mechanism of Action

Renin secretion is by the juxtaglomerular cells of the kidneys and catalyzes the conversion of angiotensinogen to angiotensin I (ATI) in the liver. ATI is converted to Angiotensin II (ATII) by angiotensin-converting enzyme (ACE) and other non-ACE pathways.[2]

ATII is the principal vasoactive peptide in the RAAS and acts on two receptors, AT1 and AT2. ATII activation of AT1 receptors causes an increase in blood pressure due to contraction of vascular smooth muscle, increased systemic vascular resistance, increased sympathetic activity, sodium (Na) and water retention as a result of increased Na reabsorption in the proximal convoluted tubule.[3] Sodium reabsorption in the proximal convoluted tubule is caused directly by ATII and indirectly by increased aldosterone production in the adrenal cortex which promotes distal Na reabsorption. Chronically high levels of ATII causes smooth muscle and cardiac muscle cell growth and proliferation, endothelial dysfunction, platelet aggregation, enhanced inflammatory responses and mediation of apoptosis. On the other hand, effects of ATII binding to AT2 receptors results in vasodilatation due to increased production of nitrous oxide and bradykinin.[4]   Furthermore, activation of AT2 receptors leads to renal sodium excretion. Agonism at AT2 receptors has anti-proliferative and cardiovascular protective effects.[3]

RAAS system blockade can take place at several levels. RAAS-blockers include direct renin inhibitors (DRIs) block production of renin, ACEIs block conversion of AT1 to AT2 by blocking angiotensin-converting enzyme, ARBs antagonize the effect of AII on AT1 receptors and aldosterone antagonists block the effect of aldosterone.[5][6]

Administration

Indications for the use of ARBs are similar to those for ACEIs. However, in patients who cannot tolerate ACEI therapy due to an ACEI-induced cough or angioneurotic edema, ARB therapy is appropriate and suggested as an alternative. Currently available angiotensin receptor blockers, their FDA approved indications and dosing for these indications are as follows:

Azilsartan

  • Available as 40 and 80 mg tablet

Dosing:

  • Hypertension: Initial dose: 20 mg by mouth once daily, maximum daily dose: 80 mg

Candesartan 

  • Available as 4 mg, 8 mg, 16 mg, 32 mg tablet

Dosing: 

  • Hypertension: Initial dose: 16 mg by mouth once daily, maximum daily dose: 32 mg
  • Heart failure: Initial dose: 4-8 mg by mouth once daily, maximum daily dose: 32 mg

Eprosartan

  • Available as 400 mg, 600 mg tablet

Dosing: 

  • Hypertension: Initial dose: 600 mg by mouth once daily, maximum daily dose: 900 mg

Irbesartan

  • Available as 75 mg, 150 mg, 300 mg tablet

Dosing: 

  • Hypertension: Initial dose: 150 mg by mouth once daily, maximum daily dose: 300 mg
  • Diabetic nephropathy: Initial dose: 75 mg by mouth once daily, maximum daily dose: 300 mg

Losartan

  • Available as 25 mg, 50 mg, and 10 mg tablet

Dosing:

  • Hypertension: Initial dose: 50 mg by mouth once daily, maximum daily dose: 100 mg
  • For stroke prevention in hypertensive patients with a history of left ventricular hypertrophy (this does not apply to African-American patients): Initial dose: 50 mg by mouth once daily, maximum daily dose: 100 mg
  • For the treatment of proteinuria or diabetic nephropathy: Initial dose: 50 mg by mouth once daily, maximum daily dose: 100 mg

 Olmesartan

  • Available as 5 mg, 20 mg, and 40 mg tablet

Dosing:

  • Hypertension: Initial dose: 20 mg by mouth once daily. Maximum daily dose: 40 mg

Telmisartan

  • Available as 20 mg, 40 mg, and 80 mg tablet

Dosing:

  • Hypertension: Initial dose: 40 mg by mouth once daily, maximum daily dose: 80 mg
  • For reduction of cardiovascular-related mortality in adults age 55 years and older who have risk factors for serious cardiovascular events and who cannot tolerate ACEI, stroke prophylaxis, and myocardial infarction prophylaxis.
  • Initial dose: 80 mg by mouth once daily, maximum daily dose: 80 mg

Valsartan

  • Available as 40mg, 80 mg, 160 mg and 320 mg tablet

Dosing:

  • Hypertension: Initial dose 80-160mg by mouth once daily, maximum daily dose 320 mg
  • For reducing cardiovascular mortality in otherwise stable patients with a history of left ventricular failure and or left ventricular dysfunction (LVD) following acute myocardial infarction.
  • Heart failure: Initial dose: 20 mg by mouth twice a day, maximum daily dose: 160 mg bid
  • Heart failure: Initial dose: 20-40 mg by mouth twice a day, maximum dose 160 mg bid

ARBs are available combined with other medications. A few examples are listed below.

valsartan and amlodipine

irbesartan and hydrochlorothiazide

losartan potassium and hydrochlorothiazide

valsartan and hydrochlorothiazide

valsartan and nebivolol

The combination of valsartan and sacubitril (neprilysin inhibitor) is available as Entrestoand approved for reducing the risk of cardiovascular death, decreasing hospitalization for heart failure in patients with chronic heart failure (NYHA Class II through IV) and for patients with reduced ejection fraction.

A few caveats to remember about the use of ARBs:

In patients with volume depletion or those who are on diuretics, correct volume depletion prior to starting these agents or start with a lower dose.

Consider using a lower dose in geriatric patients.

Consider q12-hour dosing in patients who experience diminished blood pressure response towards the end of a 24-hour dosing interval.

Adverse Effects

ARBs are generally well tolerated and have a low incidence of side effects. The incidence of angioedema and cough with ARBs is less than that with ACEIs because ARBs do not increase bradykinin levels though reports of rare cases of both exist with the use of ARBs. ARBs can cause hypotension and/or renal failure in patients whose arterial blood pressure or renal function is highly dependent on the RAAS. For this reason, these drugs are contraindicated in patients with bilateral renal artery stenosis or patients with heart failure who have hypotension.[7][8]

Contraindications

ARB therapy, as well as ACE use, during pregnancy, reduces perfusion of the fetal kidneys and are associated with renal dysgenesis, fetal oliguric or anuric renal failure, oligohydramnios, skeletal or skull deformities, pulmonary hypoplasia and death of the fetus. ARBs are FDA classified as a category D risk during pregnancy and patients who may become pregnant while taking ARBs should be advised on the importance of birth control. These patients should be educated on different options to control blood pressure should they become pregnant and need to switch to a different antihypertensive therapy. For patients who have become pregnant or think they have become pregnant, ARB therapy should be stopped immediately unless such therapy is considered life-saving for the mother.[8]

No published evidence exists on the safe use of ARBs during breastfeeding, and the effects of potential exposure to a nursing infant are unknown. Newborn infants are at theoretical risk of hypotension due to ARB as these drugs may end up in the breast milk. A decision to continue or stop breastfeeding is a necessary discussion between the primary care provider and the patient.  

ARBs may lead to hyperkalemia in patients with renal disease or patients taking agents likely to cause hyperkalemia (K+ supplements, K+ sparing diuretics, ACEIs, DRIs, non-steroidal anti-inflammatory agents) and care should be exercised prescribing ARBs in these patients or avoided altogether.

ARBs potentiate the blood pressure lowering effect of other antihypertensive drugs and may require adjustment of drug dosage of either the ARB or the other antihypertensive drugs.

Use of ARBs along with ACEIs or DRIs comes with a higher incidence of hypotension, acute renal failure or hyperkalemia. Combination use of these agents is to be avoided.

There are rare reported cases of adverse effects including urticaria, anaphylaxis, vasculitis, neutropenia, leukopenia, liver function test abnormalities and others.[9]

Monitoring

ARB therapy puts the patient at an increased risk for hypotension, renal impairment, and hyperkalemia and therefore patient's blood pressure, renal function, and serum electrolytes should be monitored closely for the duration of ARB use.[10] Primary care providers should pay specific attention to the full medication list. Lithium concentrations may increase with concomitant use of ARBs.[11][12]

Enhancing Healthcare Team Outcomes

The proper and successful management of hypertension often requires a whole-person approach that should include a nurse, primary care provider, pharmacist, and specialty physicians able to treat a patient in a wide variety of different causes and etiologies of high blood pressure. It may require diversified help from medical specialties as diabetes, heart failure, renal compromise, and obesity often accompany patients with hypertension. Although ARB therapy is one of many options in the treatment of hypertension and concomitant conditions of diabetes and or heart failure, early treatment in the face of such a diagnosis has proven to have great success in treating hypertension.[2] (Level I) If possible, high blood pressure should be diagnosed and treated early as heart disease continues to affect patients at a younger age.[13]

Along with proper pharmacotherapy in the treatment of hypertension, physicians overseeing ARB therapy should encourage patients to begin a weight loss program. Decreased inflammation and a reduction in systolic hypertension are all possible benefits of patients controlling their weight.[14] (Level ll)


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Angiotensin II Receptor Blockers (ARB, ARb) - Questions

Take a quiz of the questions on this article.

Take Quiz
Which antihypertensive agent blocks the angiotensin II receptor?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following angiotensin II receptor blockers has been found to be effective in preventing migraine headaches in a randomized, double-blind, placebo-controlled crossover trial?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following medications is NOT associated with dry cough?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is an angiotensin II receptor blocker?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 66-year-old male patient with past medical history significant for diabetic nephropathy is diagnosed with hypertension and left ventricular hypertrophy. The patient has been prescribed an angiotensin II receptor blocker. Which of the following parameters should you be most concerned about monitoring?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient has been prescribed with Telmisartan (Micardis) for her hypertension. What type of drug is Micardis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient has been prescribed with telmisartan for her hypertension. What type of drug is telmisartan?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which type of drugs is used to treat hypertension?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with arterial hypertension is started on a new medication for candidiasis. He reports his candidiasis has improved but his blood pressure is elevated. Which is true regarding the effect of the medication?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 67-year-old male with pre-existing diabetes mellitus was recently diagnosed with hypertension and started on a new blood pressure medication. After several months he developed a dry, cumbersome cough. He was then switched to a medication that is known to have a decreased incidence of dry cough with a similar mechanism of action. Why does this new medication not cause a dry cough?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 29-year-old patient with a past medical history significant for controlled hypertension presents with fatigue and several episodes of vomiting in the last 2 weeks. She also reports she has started a new relationship. A pregnancy test returns with a positive result. You notice on her active medication list she is taking candesartan. Why should she stop taking this medication?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 67-year-old male who is taking losartan 50 mg per day for hypertension develops an acute gout attack. Which of the following medications used for treating gout may place him at risk for developing hyperkalemia?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is true regarding angiotensin II receptor blockers?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 74-year-old female was recently found to have hypertension. You decide to treat her with an angiotensin II receptor blocker (ARB). What is an important consideration when prescribing an ARB to an elderly patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
The combined use of ACE inhibitors and angiotensin II receptor blockers may result in all of the following except which one?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Angiotensin II Receptor Blockers (ARB, ARb) - References

References

Hernández-Hernández R,Sosa-Canache B,Velasco M,Armas-Hernández MJ,Armas-Padilla MC,Cammarata R, Angiotensin II receptor antagonists role in arterial hypertension. Journal of human hypertension. 2002 Mar     [PubMed]
Maggioni AP, Efficacy of Angiotensin receptor blockers in cardiovascular disease. Cardiovascular drugs and therapy. 2006 Aug     [PubMed]
Cernes R,Mashavi M,Zimlichman R, Differential clinical profile of candesartan compared to other angiotensin receptor blockers. Vascular health and risk management. 2011     [PubMed]
Maggioni AP,Latini R, The angiotensin-receptor blockers: from antihypertensives to cardiovascular all-round medications in 10 years? Blood pressure. 2002     [PubMed]
Weber MA, The angiotensin II receptor blockers: opportunities across the spectrum of cardiovascular disease. Reviews in cardiovascular medicine. 2002 Fall     [PubMed]
Malacco E,Santonastaso M,Varì NA,Gargiulo A,Spagnuolo V,Bertocchi F,Palatini P, Comparison of valsartan 160 mg with lisinopril 20 mg, given as monotherapy or in combination with a diuretic, for the treatment of hypertension: the Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril (PREVAIL) study. Clinical therapeutics. 2004 Jun     [PubMed]
Rodgers JE,Patterson JH, Angiotensin II-receptor blockers: clinical relevance and therapeutic role. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2001 Apr 15     [PubMed]
Ventura M,Maraschini A,D'Aloja P,Kirchmayer U,Lega I,Davoli M,Donati S, Drug prescribing during pregnancy in a central region of Italy, 2008-2012. BMC public health. 2018 May 15     [PubMed]
Wadelius M,Marshall SE,Islander G,Nordang L,Karawajczyk M,Yue QY,Terreehorst I,Baranova EV,Hugosson S,Sköldefors K,Pirmohamed M,Maitland-van der Zee AH,Alfirevic A,Hallberg P,Palmer CN, Phenotype standardization of angioedema in the head and neck region caused by agents acting on the angiotensin system. Clinical pharmacology and therapeutics. 2014 Oct     [PubMed]
Kumar S,Ram CV, Angiotensin receptor blockers: current status and future prospects. Indian heart journal. 2007 Nov-Dec     [PubMed]
Balit CR,Gilmore SP,Isbister GK, Unintentional paediatric ingestions of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists. Journal of paediatrics and child health. 2007 Oct     [PubMed]
Prasa D,Hoffmann-Walbeck P,Barth S,Stedtler U,Ceschi A,Färber E,Genser D,Seidel C,Deters M, Angiotensin II antagonists - an assessment of their acute toxicity. Clinical toxicology (Philadelphia, Pa.). 2013 Jun     [PubMed]
Perk J,De Backer G,Gohlke H,Graham I,Reiner Z,Verschuren M,Albus C,Benlian P,Boysen G,Cifkova R,Deaton C,Ebrahim S,Fisher M,Germano G,Hobbs R,Hoes A,Karadeniz S,Mezzani A,Prescott E,Ryden L,Scherer M,Syvänne M,Scholte op Reimer WJ,Vrints C,Wood D,Zamorano JL,Zannad F, European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). European heart journal. 2012 Jul     [PubMed]
Paulis L,Foulquier S,Namsolleck P,Recarti C,Steckelings UM,Unger T, Combined Angiotensin Receptor Modulation in the Management of Cardio-Metabolic Disorders. Drugs. 2016 Jan     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of CNS-Adult Health. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for CNS-Adult Health, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in CNS-Adult Health, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of CNS-Adult Health. When it is time for the CNS-Adult Health board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study CNS-Adult Health.