Use of centrally acting sympatholytic agents in the management of hypertension

Article Abstract:

Essential hypertension is high blood pressure for which there is no clearly discernible physical cause (such as a tumor or kidney dysfunction). This condition represents the most prevalent form of hypertension. There is considerable evidence that essential hypertension is mediated, at least in part, by increased activity in the branch of the peripheral nervous system known as the sympathetic nervous system (SNS). The SNS innervates, among other organs, the heart and blood vessels. SNS activity correlates with blood pressure levels in a variety of situations; experimental activation of the SNS can result in hypertension; and blood and cerebrospinal fluid levels of norepinephrine (the neurotransmitter used by the SNS) covary with blood pressure levels. These and other forms of evidence led to the utilization of centrally acting a-agonist drugs (also called a2 agonists), which act on the central nervous system to suppress activity of the SNS, as therapeutic agents in the treatment of hypertension. Currently, four 2 agonist drugs are approved for use in the treatment of essential hypertension: methyldopa, clonidine, guanabenz acetate, and guanfacine (listed in order of release onto the market). These drugs, for the most part, are highly efficacious, are seldom contraindicated, have very few metabolic or other adverse side effects, have beneficial effects on blood flow dynamics, show little evidence of patient tolerance to their effects, are suitable for use in elderly and ill patients, and are low in cost. Recent formulations have a particularly long duration of action. Disadvantages include overlap between the therapeutic dose ranges and ranges producing dry mouth, and a tendency to cause sexual dysfunction and discontinuation syndrome (a return to the same or higher level of blood pressure upon discontinuation of the drug, coupled with anxiety, trembling, rapid heartbeat, and other evidence of excessive SNS activity). (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Causes of, Sympatholytic agents, Adrenergic alpha blockers, Adrenergic alpha-antagonists, Methyldopa

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Rapid reduction of sever asymptomatic hypertension: a prospective, controlled trial

Article Abstract:

Emergency rooms routinely reduce severe asymptomatic hypertension, high blood pressure, with orally administered antihypertensive medication. A hypertensive emergency consists of elevated blood pressure levels that threatens acute injury to an organ, such as possible damage to the small blood vessels of the eye. A study of 64 asymptomatic but severely hypertensive patients was conducted to determine if loading of the antihypertensive medication clonidine hydrochloride before beginning maintenance therapy improved or accelerated the control of blood pressure. Eighteen of the patients asked to be taken off clonidine and chlorthalidone therapy at the end the study, because of adverse side effects such as impotence and a feeling of being overly sedated. Clonidine is useful in treating acute elevations in blood pressure because it offers rapid, graded reduction of high blood pressure within an hour after administration, with maximal effect two to four hours later. The patients in this study had diastolic blood pressures of between 116 and 139 mm Hg while sitting. The results indicate that a single dose of oral clonidine can induce a reduction in blood pressure lasting over three hours. Furthermore, additional loading doses do not produce a difference in blood pressure control in the hours following the initiation of therapy. The data also demonstrate that an acute reduction in blood pressure as a result of clonidine administration is maintained in most of the patients after discharge from an emergency department. Prolonged control of blood pressure, however, is independent of treatment with a loading dose of medication. Among persons suffering from a longstanding history of hypertension, therapy should be aimed at preventing long-term, as opposed to merely acute, complications.

Research, Measurement, Dosage and administration, Blood pressure, Blood pressure measurement

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Immediate treatment of severe hypertension

Article Abstract:

Malignant hypertension, the most severe type of high blood pressure, requires immediate treatment with antihypertensive drugs. Antihypertensive drugs can be administered orally or intravenously. Intravenous (IV) infusion of nitroprusside appears to offer the best blood pressure-lowering effect, but the continuous patient monitoring required is demanding. The search for other antihypertensive drugs has led to the reassessment of oral agents for rapid blood pressure control. Physicians generally prefer to have immediate reductions in blood pressure before sending the patient home with maintenance therapy. Popular oral hypertensive agents include clonidine, which may take a few hours for effects to be seen; captopril; and more recently, nifedipine. The benefits of oral antihypertensive agents are that the results can be rapid, IV facilities are not needed, the transition from acute to long-term therapy is easier, the cost is less, and professional time and resources are saved. However, the underlying cause of the high blood pressure may be masked by immediate drug response. Blood pressures may be reduced too far and patients released a few hours after the initial intervention, leaving the patient prematurely unmonitored. There are times when IV therapy is definitely indicated, as in the control of hypertension before some types of surgery, during surgery, in the recovery room, with patients with vascular disease and patients who have had a heart attack. In the December 1989 issue of Archives of Internal Medicine, two articles discuss the efficacy of dilevalol and nicardipine for IV hypertensive drug therapy. The results of these studies suggest IV nicardipine therapy may replace nitroprusside as the drug of choice for the treatment of hypertensive emergencies.

editorial, Malignant hypertension

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