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Pharmacologic intervention in the renin-angiotensin-aldosterone (RAA) system through
inhibition of angiotensin-converting enzyme (ACE) and selective antagonism of angiotensin II
receptors has provided substantial clinical benefit in patients with hypertension. Class of agents used for this purpose are ACEIs and All antagonists respectively. Five All antagonists are currently available in Thailand for hypertension: candesartan, irbesartan, losartan, telmisartan and valsartan. They have some structural and pharmacokinetic differences. All antagonists may offer more complete inhibition of angiotensin II than ACEIs. The mechanism of action is based on selective binding to AT1 receptors, either as competitive or non-competitive (eg. candesartan) antagonist with a lack of agonist activity at this receptor. As with All antagonists, cough and angioedema will appear to be less frequent than with ACEIs. The most common adverse effects of All antagonists involved headache, dizziness and musculoskeletal pain. Such adverse effects are mild, transient and similar to those found in placebo. All antagonists also have protective effect against some organ damages. As recent studies of All antagonists and ACEIs combination therapy for heart failure indicated advantages of the combination over therapy with either class. In addition, All antagonists may exert renal protective effects in diabetic nephropathy. Therefore, All antagonists offer an alternative to ACEIs in the management of hypertension, patients with heart failure, left ventricular dysfunction after MI, and
diabetic nephropathy especially when ACEI therapy is not tolerated. Besides, losartan, unlike others in the class, has uricosuric effect which were shown in some studies that it would be benefit in thiazide treated patients as well as in cyclosporine-treated heart transplant patients. However the clinical significance must be further investigated. Thus All antagonists are currently considered as effective antihypertensive agents with a satisfied tolerability profile as well as with protective effect against some organ damages and an apparent lack of clinically important drug interaction. All these profiles combined with their simple once daily dosage regimen, make them a drug class that is likely to find favour among clinicians and patients alike, although this may be tempered somewhat by their relatively high acquisition cost. So far, whether any advantages may be attributed to any one member of the class is still unclear, due to the lack of comparative studies within the class.
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