Cardiovascular System

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Chapter: Medicinal Chemistry : Cardiovascular System

Arterial pressure is the product of cardiac output (CO) and peripheral vascular resistance. Hypertension is the most common cardiovascular disease.


Cardiovascular System

INTRODUCTION

Arterial pressure is the product of cardiac output (CO) and peripheral vascular resistance. Hypertension is the most common cardiovascular disease. The pressure elevated from the normal arterial pressure induced pathological changes in the vasculature that produces hypertrophy of left ventricle, which principally causes stroke, myocardial infarction, cardiac arrest, renal insufficiency, and dissecting aneurysm of the aorta. It is important to note that the risk of both fatal and nonfatal cardiovascular disease in adults is lowest with systolic B.P. less than 120 mm Hg and diastolic less than 80 mm Hg. In severe levels of hypertension (systolic ≥ 210 and/or diastolic ≥ 120), some patients develop arteriolopathy characterized by endothelial injury and marked proliferation of cells in intima, leading to intimal thickening and causes occlusion. This may also lead to severe microangiopathic haemolytic anaemia. Effective antihypertensive therapy will almost completely prevent haemorrhagic stroke, cardiac failure, and renal insufficiency. The usual approach to a patient with diastolic B.P. in the range of 85–94 mm Hg is to use nonpharmacological therapy as the initial strategy, which includes the life-style strategy. As the arterial pressure is the product of peripheral vascular resistance (PVR) and cardiac output, it can be lowered by the action of drugs either on the peripheral vascular resistance or CO or both.


Aetiology of Hypertension

It is important to consider specific causes in each of the case, however, because some of them are amenable to definite surgical treatment, renal artery constriction, and contraction of aorta, pheochromocytoma, Cushing’s disease, and primary aldosteronism. The patients in whom no specific cause of hypertension can be found are said to have essential hypertension. Elevated BP underlies epidemiological evidence that points to genetic inheritance, psychological stress, environmental, and dietary factors (increased salt and decreased potassium or calcium intake).

The hereditability of essential hypertension is estimated to be about 30%. Mutations in several genes have been linked to various rare causes of hypertension. Functional variations of genes for angiotensinogen, angiotensin-converting enzyme, and β2 adrenoceptor appear to contribute to some cases of essential hypertension.


Normal Regulation of Blood Pressure

According to hydraulic equation, arterial blood pressure is directly proportional to CO and PVR. 

BP = CO × PVR

BP is maintained by moment-to-moment regulation of CO and PVR, exerted at three anatomical sites, that is, arterioles, postcapillary venules, and heart.

The fourth anatomical control site, the kidney contributes to the maintenance of blood pressure regulating fluid in the body. Baroreceptor reflexes mediated by ANS are in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system to co-ordinate function at these four control sites and to maintain normal B.P. regulation. All antihypertensive drugs act by interfering with the abovespecified mechanism. They are as follows:

  1. Diuretics

    1. Thiazides and related agents

    2. Loop diuretics

    3. Potassium sparing diuretics

  2. Sympatholytic drugs

    1. Centrally acting agent

    2. Adrenergic neuron blocking agent

    3. β adrenergic antagonist

    4. α adrenergic antagonist

    5. Mixed α and β adrenergic antagonist

  3. Vasodilators

    1. Arterial vasodilators

    2. Arterial and venous vasodilators

  4. Angiotensin converting enzyme inhibitors

  5. Angiotensin II receptor antagonists


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