Hypertension is a syndrome characterized by elevated arterial blood pressure that depends on a number of factors. Some of the main factors that determine arterial blood pressure are parameters of heart rate, volume, viscosity, and electrolytic contents of circulating blood.
Normal range of blood pressure varies depending on sex and age. Moreover, various medical schools themselves determine what an acceptable value is. The etiology of 90-95% of cases of this disease are unknown, and these cases are referred to as primary or essential hypertension; treatment is of a palliative nature that is directed to lowering systolic and diastolic blood pressure, and in general, effectively permitting control of a patient's arterial blood pressure over a long period of time. During such treatment, antihy-pertensive agents can be directed at various sections of physiological systems that regulate arterial blood pressure.
The remaining 5-10% of cases of hypertension originate because of stenosis of renal arteries or constriction of the aorta, Cushing's syndrome, and pheochromocytosis. Hypertension originating from these latter conditions is called secondary hypertension. The main systems controlling the body's arterial blood pressure are the central nervous system (CNS), sympathetic ganglia, adrenergic nerve endings, vascular smooth musculature, kidneys and arterioles, and lastly, the renin-angiotensin system. Lowering arterial blood pressure can be accomplished by affecting vascular smooth musculature using hydralazine, diazoxide, minoxidil, sodium nitroprusside, diuretics, and calcium channel blockers, which relax vascular smooth musculature, thus lowering both systolic and diastolic blood pressure.
H-cholinoblockers (ganglioblockers) such as mecamylamine and trimethaphan act on autonomic ganglia to reduce blood pressure.
Lowering arterial blood pressure by acting on the adrenergic system can be accomplished by stimulating a-adrenoreceptors (clonidine, guanabenz, guanacin, and methyl-dopa), which leads to a reduction of sympathetic impulses to vessels and the heart, thus reducing cardiac output and heart rate, which consequently lowers arterial blood pressure; blocking a1-adrenoreceptors (prazosin, terazosine), the main importance of which is dilating peripheral vessels, which leads to reduced blood pressure; blocking /¡-adrenoreceptors (propranolol, athenolol, nadolol, and others), which reduce cardiac output and peripheral resistance of vessels, resulting in lower blood pressure.
Lowering blood pressure can also be done by acting on the renin—angiotensin system by using angiotensin-converting enzyme (cartopril, enalapril). These drugs block action of the angiotensin-converting enzyme, which results in less production of angiotensin II and inhibits its vasoconstricting action on arterial and venous blood vessels. Diuretics can act on the kidneys and arterioles for the purpose of lowering blood pressure. Finally, calcium channel blockers can act on smooth musculature in order to lower blood pressure (vera-pamil, diltiazem, and nifedipine).
Antihypertensive drugs can be divided into eight classes based on the mechanism of action: diuretics, /¡-adrenoblockers, centrally acting sympatholytics, peripherally acting sympatholytics, calcium channel blockers, myotropic hypotensive drugs, angiotensin-con-verting enzyme inhibitors, and calcium channel activators.
Depending on the severity of the hypertension, treatment with antihyperten-sive drugs proceeds strategically in a specific order. It is understood that this order should be flexible and open to alternative ways, but a few general principles must be adhered to.
Diuretics, ¡-adrenoblockers, or small doses of angiotensin-converting enzyme inhibitors should be used first for minor hypertension to lower blood pressure. In treating weak and moderate hypertension, it is recommended to use ¡-adrenoblockers, angiotensin-converting enzymes inhibitors, clonidine, guanabenz, guanfacine, methyldopa, prazosin, terazosin, calcium channel blockers, or reserpine. In moderate to severe hypertension, it is recommended to use hydralazine and large doses of angiotensin-converting enzyme inhibitors. In severe hypertension, guanethidine, guanadrel, and also minoxidil are used. Finally, in urgent cases of hypertension, it is recommended to use sodium nitroprusside, diazoxide, trimethaphan, or labetalol.
A universally accepted principle of antihypertension therapy is the simultaneous use of several drugs that act on the primary regions controlling arterial blood pressure, and it is generally recommended to use a combination of diuretics, adrenoblockers, angiotensin-converting enzyme inhibitors, or calcium channel blockers.
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