Angiotensin-II receptor antagonists

Brand Name Cozaar (losartan) Diovan (valsartan) 

Mechanism of Action Selective blockage of binding of angiotensin II to AT, receptors  

Drug Interactions Agents increasing serum potassium Diuretics Drugs which act on the renin-angiotensin system  

Dosage 50 mg once daily 25 mg in patients who may be volume depleted 80 mg once daily Dosage range from 80 mg to 320 mg 

These agents have toxicities similar to ACE inhibitors but less cough. Anemia has been noted in patients on calcineurin inhibitors. 

2-Butyl-4-chloro-l-[2 -(lH-tetrazol-5-yl) [1, r-biphenyl]-4-yl] methyl]-lH-imidazole-5-methanol. 

The wonderful drug losartan was developed in 1982 and sinee then being used as a potent antihypertensive agent. It specifically blocks the angiotensin II receptor. 

It has been well established and demonstrated that the potential-dependent CcP channels are solely eritieal and important in modulating the influx of Ca and henee, subsequent inhibition of Ca flow through these specifie channels results in both vasodilation as well as retarded eellular response to the prevailing eontractile stimuli. Based on the proven facts that the arterial smooth muscle is found to be more sensitive than the venous smooth muscle besides, the coronary and cerebral arterial blood vessels are observed to be more sensitive in comparison to other arterial beds .  

Consequent to these pharmacological actions, the calcium channel blockers are found to be profusely benefieial in the treatment of hypertension, and ischemic heart disease (IHD). 

Examples. Clonidine hydrochloride, hydralazine hydrochloride, methyl-dopa, diaoxide and sodium nitroprusside. 

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The Paal-Knorr furan synthesis can also be used to prepare 2,5-arylalkylfurans, as illustrated in the following example. Salimbeni produced furan 29 from dione 28 and subsequently used the furan as an intermediate for the production of angiotensin II receptor antagonists. ... 

Alkoxy-3- 4-[2-(5-tetrazolyl)phenyl]phenylmethyl -4/f-pyrido[l,2-a]py-rimidin-4-ones 417 exhibited potential angiotensin II receptor antagonistic activities (94BMCL183). 

Angiotensin II receptor antagonists—for example, irbesartan (Avapro), losartan (Cozaar), and valsar-tan (Diovan)... 

Antihypertensive drugp are contraindicated in patients with known hypersensitivity to the individual dm. When an antihypertensive is administered by a trans-derrnal system (eg, clonidine), the system is contraindicated if the patient is allergic to any component of the adhesive layer of the transdermal system. Use of the angiotensin II receptor antagonists during the second and third trimester of pregnancy is contraindicated... 

Berellini G, Cruciani G, Mannhold R. Pharmacophore, drug metabolism, and pharmacokinetics models on non-peptide ATi, AT2, and AT1/AT2 angiotensin II receptor antagonists. J Med Chem 2005 48 4389-99. 

Electrostatic potential of a new angiotensin II receptor antagonist from X-ray diffraction and ab initio calculations... 

Salimbeni, A., Canevotti, R., Paleari, E, Poma, D., Caliari, S., Fici, E, Cirillo, R., Renzetti, A.R., Subissi, A., Belvisi, L., Bravi, G., Scolastico, C. and Giachetti, A. (1995) N-3-substituted pyrim-idinones as potent, orally active, AT, selective angiotensin II receptor antagonists, J. Med. Chem., 38, 4806 1820. 

Destro, R. and Soave, R. (1995) A new non-peptide angiotensin II receptor antagonist, Acta Crystallogr., C51, 1383-1385. 

Angiotensin II receptor antagonists. These agents promote vasodilation (1 TPR), increase sodium and water excretion, and, therefore, decrease plasma volume (1 CO). 

Compound 686 (PNU-97018) is an orally active nonpeptide angiotensin II receptor antagonist without any agonistic activity that has an insurmountably high antihypertensive effect <2002CPB1022, 1995JEP1042, 1995MI880>. 

Attempts to counteract tolerance development include the use of thiols such as N-acetylcysteine, antioxidants such as vitamin C and vitamin E, and angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists. Other approaches to decreasing the development of tolerance include intermittent therapy... 

Recent studies with quinoline-4-carboxylic acid angiotensin II receptor antagonists have confirmed the interest of (oxodioxolyl)methyl esters as prodrugs with improved oral bioavailability and efficacy in laboratory animals [79], Olmesartan, another angiotensin II receptor antagonist, has also been derivatized to a (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl carboxylate designated as olmesartan medoxomil [80], In this case, both human serum albumin and arylesterase (presumably EC 3.1.1.2, although paraoxonase cannot be excluded) were shown to be involved in hydrolysis. 

Pronounced bradycardia with a beta blocker pronounced hypotension with an angiotensin II receptor antagonist... 

Competitive blocker of a-adrenergic receptors in heart and blood vessels Inhibits the enzyme HMG-CoA reductase and reduces the biosynthesis of cholesterol Acts as an angiotensin II receptor antagonist Inhibits the synthesis of prostaglandins via the selective inhibition of the enzyme cyclooxygenase-2... 

Angiotensin-II-receptor antagonists These block the binding of this messenger to its receptors on the two target tissues, i.e. smooth muscle in the arterioles and the aldosterone-secreting cells in the adrenal cortex. 

Kiyama, R., Honma, T., Hayashi, K., Ogawa, M., Hara, M., Fujimoto, M., and Fujishita, T. Angiotensin II receptor antagonists. Design, synthesis, and in vitro evaluation of dibenzo[a,d]cycloheptene and dibenzo[b,f oxepin derivatives. 

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