Angiotensins antagonists

Nitrates and hydralazine have been used in patients with congestive heart failure. An angiotensinconverting enzyme inhibitor such as lisinopril increases the left ventricular ejection fraction in 

FIGURE 35.8 Amrinone exerts positive inotropic and vasodilating actions. AMP = adenosine monophosphate AC = adenylate cyclase PDE = phosphodiesterase Gs = stimulatory guanine nucleotide-binding regulatory protein. 

In addition, a vasodilator in combination with an angiotensin-converting enzyme inhibitor has been used in congestive heart failure. The vasodilators may be classified as venodilators, arterial dilators, or balanced-type vasodilators. 

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Reaction of the imidazole (7-4) with the benzofuran derivative (6-7) leads to the displacement of the benzylic halogen and the formation of the alkylation product (8-1). Treatment of that intermediate with trifluoroacetic acid breaks open the urethane to afford the corresponding free amine. This is allowed to react with ttiflic anhydride to afford the trifluoromethyl sulfonamide (8-2). The ester group on the imdidazole is then saponified, and the newly formed acid is reacted with carbonyl diimidazole. Reaction with ammonia converts the activated carboxyl group to the amide. There is thus obtained the angiotensin antagonist saprisartan (8-3) [6]. 

Angiotensin receptor blockers (ARBs) Antagonize All effects at ATj receptors Like ACE inhibitors Like ACE inhibitors used in patients intolerant to ACE inhibitors Oral duration 6-8 h Toxicity Hyperkalemia angioneurotic edema Interactions Additive with other angiotensin antagonists... 

Aliskiren is the most advanced of these and the first to be approved for the treatment of hypertension. In healthy subjects, aliskiren produces a dose-dependent reduction in plasma renin activity and Ang I and II and aldosterone concentrations. In patients with hypertension, many of whom have elevated plasma renin levels, aliskiren suppresses plasma renin activity and causes dose-related reductions in blood pressure similar to those produced by ACE inhibitors (Figure 17-3). The safety and tolerability of aliskiren appear to be comparable to angiotensin antagonists and placebo. 

Diovan Valsartan Novartis hypertension angiotensin antagonist 736 (63%)... 

Angiotensin antagonists inhibit angiotensin-converting enzyme (ACE), resulting in inhibiting the formation of angiotensin II (vasoconstrictor) which blocks the release of aldosterone and causes lowered peripheral resistance. 

Angiotensin antagonists (Angiotensin-converting enzyme inhibitors) and ACE inhibitors lower blood pressure and are used to treat heart failure by causing the excretion of sodium and water. ACE inhibitors block the release of aldosterone. Aldosterone causes the retention of sodium. Cardiac output and heart rate remain unchanged. ACE inhibitors are administered to patients with elevated serum rennin levels. ACE inhibitors can cause angioedema in which the mouth, throat, lips, eyelids, hands, and feet swell. 

Describe the differences between the two types of angiotensin antagonists. 

As indicated in Figure 11-2, the compensatory responses can be counteracted with p-blockers or reserpine (for tachycardia) and diuretics or angiotensin antagonists (for salt and water retention). 

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