Other Agents

Direct vasodilators such as hydralazine and minoxidil represent additional alternative agents used for patients with resistant hypertension. Primarily acting to relax smooth muscles in arterioles and activate baroreceptors, their use in the absence of concurrently administered P-blockers and diuretics is uncommon. This is due to the need to offset their tendency to cause reflex tachycardia and fluid retention. Other, more rare adverse effects include hydralazine-induced lupus-like syndrome and hypertrichosis from minoxidil. Finally, reserpine, although slow to act, represents another rarely used alternative agent for those who are recalcitrant to more standard therapy. This agent is a long-acting depleter of the catecholamine norepinephrine from sympathetic nerve endings and via blockade of norepinephrine transport into its storage granules which causes reduced sympathetic tone leading to reductions in PR. Reserpine's association with numerous side effects including gastric ulceration, depression, and sexual side effects has limited its perception as a useful agent, but in low doses it can be well tolerated. In fact, the SHEP trial86 demonstrated the BP lowering effectiveness of low-dose reserpine (0.05 mg/day) when combined with a diuretic, with similar cardiopulmonary and psychosocial side effects between the treatment and placebo groups. In addition, low-dose reserpine was also used as add-on therapy in the ALLHAT trial. Two additional agents, guanethidine and guanadrel, act as postganglionic sympathetic inhibitors inhibiting the release of norepinephrine as well as depleting norepinephrine from these nerve terminals. However, these agents have little role in the management of hypertension because of significant adverse effects.

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