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Why are L-type calcium channels valid targets for the treatment of hypertension - Essay Example

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Hypertension is a common problem world wide with devastating complications. Several classes of antihypertensives are available for use and they include ACE inhibitors, thiazide diuretics, beta blockers, angiotensin II receptor antagonists and calcium channel blockers…
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Why are L-type calcium channels valid targets for the treatment of hypertension
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Download file to see previous pages Hypertension is a common problem world wide with devastating complications. Several classes of antihypertensives are available for use and they include ACE inhibitors, thiazide diuretics, beta blockers, angiotensin II receptor antagonists and calcium channel blockers. Which is the most ideal antihypertensive agent has been the subject of several large studies and to date, no ideal antihypertensive agent has been declared. The main goal of antihypertensive therapy is to decrease the risk of endpoints of hypertension, namely stroke, heart failure and myocardial ischemia. The type of medication administered depends on the age of the person and comorbid conditions. Other influencing factors include cost of medicines and tolerance to medications. For several years, L-calcium channel blockers have been the first line antihypertensive drugs for hypertensive patients (Klabunde, 2008). Calcium channel blockers are those drugs which prevent the entry of calcium into the cells of the heart and the blood vessels. By doing so, the muscles of the heart and blood vessels relax, resulting in dilatation of blood vessels and lowering of blood pressure. Some calcium channel blockers cause decrease the heart rate, thus further reducing the blood pressure. Calcium channel blockers not only reduce blood pressure, but also relieve angina and irregular heart beat. The calcium channel blockers which are currently approved bind to the L-type calcium channels that are located on the cardiac myocytes, vascular smooth muscle and cardiac nodal tissue, the atrioventricular and sinoatrial nodes. The channels regulate the influx of calcium into the muscle cells and in turn stimulate the contraction of the smooth muscles and the cardiac myocyte. In the nodal tissues of the heart, the L-type channels have major role to play in the pacemaker currents and in the phase 0 of action potentials. Thus, blocking of calcium entry into the cells causes vasodilation, negative ionotropy, negative dromotropy at the atrioventricular node, and negative chronotropy (Klabunde, 2008). Calcium channels are voltage dependent and opening of these channels permits influx of the calcium ions across the plasma membrane, thus triggering various physiological processes. The channels are distributed widely in the cardiovascular system, constituting main routes for entry of the calcium ions essential for excitation and contraction. In this regard, as of now, ten unique alpha-1 subunits have been identified and these are groups in 3 families: CaV1, CaV2, and CaV3. These encode the low-voltage–activated T-type and the high-voltage–activated L-, N-, P/Q- and R-type Ca2+ channels (Ge and Ren, 2009). The most common of these are the L-type and they are abundant in the peripheral vasculature and heart, constituting preferred target for initial calcium channel antagonists in antihypertensive treatment. T-channels are present in various cells like cardiomyocytes, neurons, endocrine cells and vascular smooth muscle cells. They have a role in several physiological processes (Ge and Ren, 2009). There is some evidence that T-channel blockade also is useful in the management of hypertension. The drugs developed for this purpose are dihydropyridines like benidipine, efonidipine, nilvadipine, manidipine and benzimidazole mibefradil (Ge and Ren, 2009). These drugs have vasodilatory properties similar to L-channel blockers and some of them may antagonise both L-channels and T-channels. However, there is yet uncertainity about the exact role of T-channel blockers in controlling vascular tone and decreasing hypertension (Toba et al, 2011). There are basically 3 classes of calcium channel blockers and they are: 1. Dihydropyridines: These are selective to smooth muscles of the blood vessels. Hence, they are mainly used to decrease systemic vascular resistance and arterial pressure. They are also primarily used to treat hypertension. They are not useful in the treatment of angina because reflex cardiac ...Download file to see next pagesRead More
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