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Antihypertensive drugs are organized around a clinical indication—the need to treat a disease—rather than a receptor type. The drugs covered in this unit have a variety of mechanisms of action including diuresis, sympathoplegia, vasodilation, and antagonism of angiotensin, and many agents are available in most categories. A single renin inhibitor has recently been added to the drugs used in this condition.

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Less than 20% of cases of hypertension are due to ("secondary" to) factors that can be clearly defined and corrected. This type of hypertension is associated with pheochromocytoma, coarctation of the aorta, renal vascular disease, adrenal cortical tumors, and a few other rare conditions. Most cases of hypertension are idiopathic, also called "primary" or "essential" hypertension. The strategies for treating idiopathic hypertension are based on the determinants of arterial pressure (see Figure 6–4). These strategies include reductions of blood volume, sympathetic effects, vascular smooth muscle tension, and angiotensin effects. Unfortunately, the baroreceptor reflex and the renin response in primary hypertension are reset to maintain the higher blood pressure. As a result, they respond to lower blood pressure with compensatory homeostatic responses, which may be significant (Table 11–1). As indicated in Figure 11–1, these compensatory responses can be counteracted with β blockers and diuretics or angiotensin antagonists.

Table 11–1 Compensatory Responses to Antihypertensive Drugs.
Figure 11–1

Compensatory responses (orange boxes) to decreased blood pressure when treating hypertension. The initial treatment that causes the compensatory responses might be a vasodilator. Arrows with minus signs indicate drugs used (white boxes) to minimize the compensatory responses. ACE, angiotensin-converting enzyme.

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Baroreceptor reflexPrimary autonomic mechanism for blood pressure homeostasis; involves sensory input from carotid sinus and aorta to the vasomotor center and output via the parasympathetic and sympathetic motor nerves
Catecholamine reuptake pump (norepinephrine transporter [NET])Nerve terminal transporter responsible for recycling norepinephrine after release into the synapse
Catecholamine vesicle pumpStorage vesicle transporter that pumps amine from cytoplasm into vesicle; also called vesicle monoamine transporter (VMAT)
End-organ damageVascular damage in heart, kidney, retina, or brain
Essential hypertensionHypertension of unknown etiology; also called primary hypertension
False transmitterSubstance, for example, octopamine, stored in vesicles and released into synaptic ...

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