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Olmesartan medoxomil propyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl] imidazole-4-carboxylate (Benicar, Olmetec) uses the tetra-zole ring system as its acidic system, which participates in receptor binding.14 When administered to a patient, the drug is rapidly and completely bioactivated by ester hydrolysis of the medoxomil during absorption from the gastrointestinal tract. Once the prodrug is converted to the active form, virtually no further metabolism occurs. In September 2007, the Food and Drug Administration (FDA) approved its use as a combination product with the calcium channel blocker am-lodipine for the management of hypertension. This combination product is sold under the tradename of Azor.

Valsartan. Valsartan, N-(1-oxopentyl)-N-[[2'-(1#-tetra-zol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-l-valine (Diovan), like losartan, possesses the acidic tetrazole system, which most likely plays a role, similar to that of the acidic groups of an-giotensin II, in binding to the angiotensin II receptor. In addition, the biphenyl system that serves to separate the tetrazole from the aliphatic nitrogen is still present. In addition, there is a carboxylic acid side chain in the valine moiety that also serves to bind to the angiotensin II receptor.15

o renin inhibitors

Renin is a circulating enzyme that is secreted by the kidneys in response to decreases in glomerular filtration rate, which is typically a result of low blood volume. It is a 340-amino acid protein that participates in the renin-angiotensin system. It is responsible for cleaving angiotensinogen, which is produced in the liver, to angiotensin I. As indicated previously in this chapter, angiontensin I is converted to an-giotensin II, which plays an important role in regulating blood pressure, among other physiological events. Inhibitors of renin have usefulness in managing cardiovascular diseases such as hypertension and heart failure because of their ability in reducing the influence on the renin-angiotensin system through reduced biosynthesis of angiotensin II and other bioactive intermediates.16

Although this drug target has been investigated for more than 30 years, it represents the first new class of orally active antihypertensive agents and joins at least seven other classes of antihypertensive drugs. The other classes, as described in Chapter 19, include diuretics, ^-blockers, S-blockers, calcium channel blockers, as well as those discussed in this chapter and include ACE inhibitors, ARBs, and aldosterone receptor antagonists.

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