Diuretics
Diuretics have long been recommended as first-line drug for hypertension and relatively safe and effective (Mancia,et al., 2007). Most of diuretics agents lowering blood pressure by depleting the body of sodium and reducing blood volume. Some drugs also lower blood pressure by vasodilation. Diuretics blood pressure lowering effects take at two stages: (1) reduction of total blood volume and therefore cardiac output; initially causes increase of peripheral vascular resistance; (2) when CO returns to normal level (6-8 weeks) PVR declines (Beevers,et al.,2007).Based on their mechanism of site action, there are six different classes of diuretics each acts on a different segment of nephron (kidney tubule) and modulate a specific function. These are carbonic anhydrase inhibitors, Thiazide diuretics, K-sparing diuretics, loop diuretics, Antidiuretic Hormone (ADH) Antagonists and osmotic diuretics. All of them interfere with renal Na+-reabsorption at various segments of the nephron. For instance, carbonic anhydrase inhibitors exert its diuretic effect by inhibition of renal carbonic anhydrase enzymes (Maren, 1977). Thiazide diuretics, such as hydrochlorothiazide, inhibit NaCl reabsorption from the luminal side of epithelial cells in the distal convoluted tubule by blocking the Na+/Cl- transporter. Diuretics inhibit the Na+-Cl-symporter, perhaps by competing for the Cl- binding site (Odlind, O., 1984). Most of loop diuretics are sulfonamide derivatives and inhibit the Na-K-2Cl- symporter in the thick ascending limb of the kidney. Some K-sparing diuretics (amiloride, triamterene) directly interfere with Na+ entry through the sodium-selective (ENaC) ion channels in the apical membrane of the collecting tubule and others K-sparing diuretics (spironolactone, eplerenone) bind to aldosterone receptors (mineralocorticoid receptors) and may also reduce the intracellular formation of active metabolites of aldosterone. Antidiuretic Hormone (ADH) Antagonists (lithium and demeclocycline) inhibit the effects of ADH in the collecting tubule and reduce the formation of cyclic adenosine monophospate (cAMP) in response to ADH and also to interfere with the actions of cAMP in the collecting tubule cells. Osmotic Diuretics (mannitol) act at proximal tubule and descending limb of Henle's loop. Osmotic diuretics reduce increased intracranial pressure and reduce water observation at those segments (Odlind, O., 1984).
Beta-blockers
All beta-adrenoceptor–blocker (BAB) are useful for lowering blood pressure in mild to moderate hypertension. Beta-blockers are antihypertensive agents that act on peripheral nervous system. In addition, beta-blockers are antagonizing the effects of sympathetic nerve stimulation or circulating catecholamine at beta-adrenoceptors which are widely distributed throughout body systems. Beta1-receptors are predominats in the hearts and kidneys. Beta2-receptors are predominant in other organ such as the lung, peripheral blood vessel and skeletal muscle. Beta-blockers bind to beta-adrenergic receptors and antagonize the effects of the endogenous agonists norepinephrine and epinephrine (Triposciadis, etal., 2009). Blockage of beta1-receptors inhibit the the release of renin from juxta-glomerular cells and thereby reduce the activity of RAAS. Blockage of beta1 receptor in the heart (Sino-atrial node reduces heart rate thereby reduce cardiac output (negative chronotropic effect) and blockage of beta1-receptors in the myocardium decrease cardiac contractility (negative inotropic effect). Blockage of b1-receptors in the brain where the effect is to reduce the activity of the sympathetic nervous system, reducing the release of noradrenaline at the β-receptors thereby decreases sympathetic nervous system activity (Prichard, et al., 1980). It is notable that the major effects of β-adrenoceptor antagonists are seen when sympathetic activity is high (physical activity, stress) and understandabletherefore that the argument for using these drugs is greatest in patients where excess sympathetic activity contributes most to their hypertension(Beevers, et al.,2007). However, the competitive inhibition of beta-receptors leads to reduction in cardiac output, attenuation in renin release, adrenergic neuroninhibiting effects and decrease in central sympathetic nervous activity, but the exact BP lowering mechanism of beta-blockers is not fully known (Prichard, et al., 1980). Not all β-adrenoceptor antagonists are the same. There are a large number of β-adrenoceptor antagonists from which a prescriber must choose the most appropriate for each individual (Frishman, W.H., 1988). Significant differences are to be found in selectivity between β-adrenoceptor subtypes, selectively between α- and β-adrenoceptors, and partial agonism. β1–β2-subtype selectivity of β-adrenoceptorantagonists. The early β-adrenoceptor antagonist propranolol is equally effective at both β1- and β2- subtypes.
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