Angiotensin Receptor Blocker
By Dr. Mahnoor Javed (Pharm-D)
ANGIOTENSIN II is a very potent chemical formed in the blood that causes muscles surrounding blood vessels to contract, thereby narrowing the vessels. This narrowing increase the pressure within the vessels and can cause high blood pressure (hypertension). Angiotensin receptor II blockers are medications that block the action of angiotensin II by preventing angiotensin II receptors on the muscles surrounding blood vessels. As a result, blood vessels enlarge (dilate) and blood pressure is reduced. Reduced blood pressure helps the heart to pump blood easily and can improve heart failure. ARBs have effects that are similar to angiotensin converting enzyme (ACE) inhibitors, but ACE inhibitors act by preventing the formation of angiotensin II rather than by blocking the binding of angiotensin II to muscles on blood vessels.
Examples of Angiotensin receptor blockers
The ARBs currently available are:
- Telmisartan (Tasmi, Telsan)
- Valsartan (Diovan)
- Candesartan (Advant, Blopress)
- Ibersartan (Aprovel, Avapro)
- Losartan (Cozaar, Eziday)
- Olmesartan (Benicar)
- Azilsartan (Edarbi)
- Eprosartan (Tevetan)
Mechanism of Action
The mechanism of action is very different from ACE inhibitors. ARBs are receptor antagonist that block type 1 angiotensin II (AT1) receptors on blood vessels and other tissues such as the heart. These receptors are coupled to the Gq-protein and IP3 signal transduction pathway that stimulates vascular smooth muscles contraction. Because ARBs do not inhibit ACE, they do not cause an increase in bradykinin, which contributes to the vasodilation produced by ACE inhibitors and also some of the side effects of ACE inhibitors (cough and angioedema).
Clinical Applications
- ARBs are used for controlling high blood pressure, treating heart failure and preventing kidney failure in people with diabetes or high blood pressure.
- ARBs also may prevent diabetes and reduce the risk of stroke in patients with high blood pressure and an enlarged heart.
- ARBs also may prevent the recurrence of atrial fibrillation.
ARBs have the following actions:
- Dilate arteries and veins and thereby reduce arterial pressure and preload and afterload on the heart.
- Down regulate sympathetic adrenergic activity by blocking the effects of angiotensin II on the sympathetic nerve release and reuptake of norepinephrine.
- Promote renal excretion of sodium and water (natriuretic and diuretic effects) by blocking the effects of angiotensin II in the kidney and by blocking angiotensin II stimulation of aldosterone secretion.
- Inhibit cardiac and vascular remodeling associated with chronic hypertension, heart failure and myocardial infarction.
Therapeutic Uses Of Angiotensin II Receptor Antagonists
All ARBs are approved for the treatment of hypertension. In addition, irbesartan and losartan are approved for diabetic nephropathy, losartan is approved for stroke prophylaxis, and valsartan is approved for heart failure patients who are intolerant of ACE inhibitors. The efficacy of ARBs in lowering blood pressure is comparable with that of other established antihypertensive drugs, with an adverse-effect profile similar to that of placebo. ARBs also are available as fixed-dose combinations with hydrochlorothiazide.
Losartan is well tolerated in patients with heart failure and is comparable to enalapril with regard to improving exercise tolerance. Both valsartan and candesartan reduce mortality and morbidity in heart failure patients. Current recommendations are to use ACE inhibitors as first-line agents for the treatment of heart failure and to reserve ARBs for patients who cannot tolerate or have an unsatisfactory response to ACE inhibitors. At present, there is conflicting evidence regarding the benefit of combining an ARB and an ACE inhibitor in heart failure patients.
In part via blood pressure–independent mechanisms, ARBs are renoprotective in type 2 diabetes mellitus and many experts now consider them the drugs of choice for renoprotection in diabetic patients. ARBs are superior to B1 adrenergic receptor antagonists in reducing stroke in hypertensive patients with left ventricular hypertrophy. Irbesartan appears to maintain sinus rhythm in patients with persistent, long-standing atrial fibrillation. Losartan is reported to be safe and highly effective in the treatment of portal hypertension in patients with cirrhosis without compromising renal function.
Adverse Effects
ARBs are well tolerated by most people.
The most common side effects are:
- Cough
- Elevated potassium levels in the blood (hyperkalemia)
- Low blood pressure
- Dizziness
- Headache
- Drowsiness
- Diarrhea
- Abnormal taste sensation (metallic or salty taste)
- Rash
- Orthostatic hypotension
- Fatigue
- Indigestion
- Increase blood glucose levels.
- Flu-like symptoms
Serious side effects
The most serious but rare side effects are:
- Kidney failure
- Liver failure
- Serious allergic reaction
- Decrease in WBCs
- Angioedema
- Rhabdomyolysis
The incidence of discontinuation of ARBs owing to adverse reactions is comparable with that of placebo. Unlike ACE inhibitors, ARBs do not cause cough, and the incidence of angioedema with ARBs is much less than with ACE inhibitors.
As with ACE inhibitors, ARBs have teratogenic potential and should be discontinued before the second trimester of pregnancy. ARBs should be used cautiously in patients whose blood pressure or renal function is highly dependent on the renin–angiotensin system (e.g., renal artery stenosis). In such patients, ARBs can cause hypotension, oliguria, progressive azotemia, or acute renal failure.
ARBs may cause hyperkalemia in patients with renal disease or taking K+ supplements or K+-sparing diuretics.
ARBs enhance the blood pressure–lowering effect of other antihypertensive drugs, a desirable effect but one that may necessitate dosage adjustment.
Contraindications
- Pregnancy
- ACE Inhibitors
- Patients with bilateral renal artery stenosis may experience renal failure if ARBs are administered.
Interactions
- Since ARBs may increase blood levels of potassium, the use of potassium supplements may result in excessive blood potassium levels and cardiac arrhythmias.
- They increase blood concentration of lithium.
- Rifampin reduces the blood levels of losartan, fluconazole reduces the conversion of losartan to its active form.
- ARBs should not be combined with ACE inhibitors because such a combination increases the risk of hypotension, hyperkalemia and renal impairment.
How should I take them?
- ARBs can be taken on full or empty stomach. Follow the label instructions while taking these medications. The number of doses you take each day, the time allowed between doses and how long one should continue the medication depends on the type of ARB prescribed as well as the condition.
- While taking this medication, have your blood pressure and kidney function checked regularly, as recommended by your doctor.
References
Basic & Clinical Pharmacology
(12th edition by Bertram G. Katzung, Susan B. Masters, and Anthony J. Trevor)
www.medicinenet.com/angiotensin_ii_receptor_blockers/article.htm
https://cvpharmacology.com/vasodilator/ARB
https://www.webmd.com/hypertension-high-blood-pressure/guide/treatment-angiotensin-ii
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