Angiotensin II Receptor Blockers (ARB)

• What are angiotensin II receptor blockers?
• How do they work?
• What are they used for?
• Side effects
• Precautions
  • Excessive hypotension
  • Hyperkalaemia
  • Primary hyperaldosteronism
  • Pregnancy
  • Breastfeeding
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)

What are angiotensin II receptor blockers?

Angiotensin II receptor blockers (ARBs) are a class of drugs used to treat hypertension.  Examples of common ARBs include candestartan, lsartan and telmisartan.  ARBs are believed to reduce blood pressure to the same extent as other antihypertensive drug classes such as, β-blockers and angiotensin converting enzyme inhibitors (ACEi).

How do angiotensin II receptor blockers work?

Angiotensin II receptor blockers bind to the Angiotensin I Receptor (AT1) and prevent the effects of angiotensin II being mediated.  AT1 mediate most of the effects of angiotensin II and those that are mediated by angiotensin receptor II are not yet established.  ARBs bind specifically to the AT1 receptor to reduce hypertension.  They have a highly specific affinity for AT1.  The biological effects of angiotensin II are contraction of blood vessels, aldosterone release, sympathetic nerve stimulation and cell growth.  These effects are inhibited by ARBs.

What are angiotensin II receptor blockers used for?

ARBs are used to treat hypertension and are especially used by those who cannot tolerate ACEi. They are also used to slow the worsening of renal disease in type II diabetics.  The maximum antihypertensive effect usually occurs around 4-6 weeks after treatment has been started.

Possible side effects

Common side effects include:

• Headaches
• Hyperkalaemia
• Dizziness

Infrequent side effects include:

• Orthostatic hypotension upon the first dose
• Diarrhoea
• Rash
• Muscle cramps
• Myalgia
• Back pain
• Insomnia
• Dyspepsia
• Reduced kidney function

Rare side effects include:

• Cough
• Migraine
• Angioedema

Precautions

Several pre-existing conditions may restrict the use of ARBs.  If not noted they could lead to serious damage or lead to the development of other conditions.

Excessive hypotension

Hypotension is when you have a lower blood pressure than normal. There is an increased risk of low blood pressure when taking ARBs and if you have a reduced volume or sodium level or have either aortic stenosis or mitral valve stenosis.

Hyperkalaemia

Hyperkalaemia is when there is an excess of potassium in the blood.  This can lead to potentially fatal arrythmias of the heart.  When taking ARBs there is an increased risk of hyperkalaemia if you are also taking drugs that increase potassium concentrations (eg cyclosporin).  It is advised that if taking drugs which increase potassium concentrations to either prevent use by switching to another drug or to monitor potassium levels carefully.

Problems with kidneys can also lead to increased risk of hyperkalaemia.  As a result, it is advised that a lower starting dose should be used and monitoring of potassium levels should also occur.

Primary hyperaldosteronism 

Primary hyperaldosteronism or Conn’s Syndrome is the excessive production of aldosterone occurring independently of the renin angiotensin system.  If the you have this condition then it can reduce the antihypertensive effect of the drug.

Pregnancy

ARBs should be avoided if pregnant as it may adversely effect the developing baby.  It is recommended that an alternative antihypertensive should be used instead. ARBs are part of the ADEC category D.

Breastfeeding

Guidelines regarding breastfeeding and ARBs use have not been produced as yet.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 

NSAIDs like cyclooxgenase-2 inhibitors can reduce the antihypertensive effect.

References

1. Chapter 6 – Cardiovascular Drugs, 6.4 Antihypertensives, 6.4.5 Angiotensin II antagonists In: Australian Medicines Handbook. Australia: Australian Medicines Handbook Pty. Ltd.; 2007
2. Costa FV, Telmisartan Standing Out in a Crowded Contest? High Blood Press Cardiovasc Prev 2006 13 (3): 85-94
3. Fitchett D, Clinical trial update: focus on the ONTARGET study. Vascular Health and Risk Management 2007 3(6) 1-8
4. Weber MA Chapter C137-Angiotensin Receptor Blockers In: Izzo JL, Sica DA, Black HR editors. Hypertension Primer: the Essentials of High Blood Pressure: Basic Science, Population Science, and Clinical Management: Lippincott Williams & Wilkins; 2008
5. Cozaar In: Donohoo E editor MIMS Online.[online] MIMS Australia Pty Ltd 2003. Available from: URL: http://www.mims.com.au
6. Part of Chapter 5.2- Adrenal imaging, Primary hyperaldosteronism (Conn’s syndrome) In: Wass JAH, Shalet SM, Gale E et al. editors. Oxford Textbook of Endocrinology and Diabetes: Oxford University Press; 2002 
7. Chapter 9 Endocrinology, The adrenal gland: Hyperaldosteronism In: Longmore M, Wilkinson IB, Rajagopalan SR editors. Oxford Handbook of Clinical Medicine: Oxford University Press; 2004
8. Prescribing medicines in pregnancy [online]. 2007 [cited 2008 Apr 6]. Available from: URL: http://www.tga.gov.au/docs/html/medpreg.htm