Overview Of Antihypertensive Therapy

INTRODUCTION:- HISTORICAL BACKGROUND OF ANTIHYPERTENSIVE THERAPY
Antihypertensive therapy with the conventional drugs such as thiazide diuretics,beta –adrenoreceptor antagonists and Calcium channel antagonist (CCA ) based regimens can reduce the risk of stroke and other cardiovascular events. The drugs used as first line therapy in both younger and elderly patients include the conventional drugs such as diuretics, CCA or ACE inhibitors based regimens[6][7]
ACE inhibitors such as Captopril and enalapril are used clinically for the treatment of hypertension and congestive heart failure(CHF). Despite the fact that ACE inhibitors have met with a high degree of success, ACE is a nonspecific protease responsible for degradation of bradykinin as well as other peptides such as substance P and the enkephalins. The dry cough and the instances of angioedema have been proposed to be the result of lack of specificity of ACE , more specifically these side effects have been attributed to bradykinin potentiation.[8][9]
Inhibition of the terminal step in the RAS i.e. Ang II receptor blockade, offers a highly specific approach to inhibition of the system regardless of the source of Ang II. Also, since ACE would not be affected by such agents, potentiation of bradykinin and hence cough or angioedema by this mechanism would not be expected during therapy with an Ang II blocker[10]. The angiotensin receptors blockers such as angiotensin II type 1 (AT1)receptor antagonists has a number of other advantages also such as excellent record of tolerability, having few drug interactions or contraindications and given by once daily administration results in improved drug compliance. AT1 receptor antagonists can be recommended as the first line therapy in el...

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...r those derived from 4-pyridones and 4-alkoxypyridines were considered, both of which have comparable acceptor potential to that of imidazole. As outlined in Fig., incorporation of the other key features necessary for receptor binding suggested as target derivatives of 4-quinolone and 4-alkoxyquinoline.

iv. Pyrimidinone compounds
On the basis of the comparative analysis of the molecular electronic potential distributions and overlay studies employing a model of Ang II derived from theoretical calculations , a new series of N-3-substituted pyrimidinones have been prepared. The data collected indicated that the pyrimidinone ring successfully replaced the tetrasubstituted imidazole of Losartan. The introduction of an aryl methyl group on the nitrogen atom adjacent to the carbonyl group of the pyrimidinone ring favourably influences the activity particularly in vivo.