Clinical Pharmacology of Centrally Acting Antihypertensive Agents

Weber, Michael A.

doi:10.1002/j.1552-4604.1989.tb03387.x

Cited by 6 publications

(3 citation statements)

References 27 publications

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“…The choice of this agent rests with the understanding that it has a distinctive pharmacological mechanism for BP reduction that theoretically should have potentiated the effects of the other medications. [15][16][17] Spironolactone was not selected because, when this study was designed, it was felt that the available data did not support the use of this drug for all of the patients with RHTN. Guanfacine at the dose used (1 mg) did not lower BP substantially in our trial.…”

Section: Discussionmentioning

confidence: 99%

Divergent Results Using Clinic and Ambulatory Blood Pressures

et al. 2010

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Abstract-Patients with resistant hypertension are at increased risk for cardiovascular events. The addition of new treatments to existing therapies will help achieve blood pressure (BP) goals in more resistant hypertension patients. In the current trial, 849 patients with resistant hypertension receiving Ն3 antihypertensive drugs, including a diuretic, at optimized doses were randomized to the selective endothelin A receptor antagonist darusentan, placebo, or the central ␣-2 agonist guanfacine. The coprimary end points of the study were changes from baseline to week 14 in trough, sitting systolic BP, and diastolic BP measured in the clinic. Decreases from baseline to week 14 in systolic BP for darusentan (Ϫ15Ϯ14 mm Hg) were greater than for guanfacine (Ϫ12Ϯ13 mm Hg; PϽ0.05) but not greater than placebo (Ϫ14Ϯ14 mm Hg). Darusentan, however, reduced mean 24-hour systolic BP (Ϫ9Ϯ12 mm Hg) more than placebo (Ϫ2Ϯ12 mm Hg) or guanfacine (Ϫ4Ϯ12 mm Hg) after 14 weeks of treatment (PϽ0.001 for each comparison). The most frequent adverse event associated with darusentan was fluid retention/edema at 28% versus 12% in each of the other groups. More patients withdrew because of adverse events on darusentan as compared with placebo or guanfacine. We conclude that darusentan provided greater reduction in systolic BP in resistant hypertension patients as assessed by ambulatory BP monitoring, in spite of not meeting its coprimary end points The objective of reaching this goal is reduction of cardiovascular and renal events. Many patients can achieve this BP target with 1 or 2 antihypertensive drugs in addition to appropriate lifestyle changes. However, patients with treatment-resistant hypertension (RHTN) require full doses of Ն3 medications that act by complementary mechanisms, including a diuretic, to achieve these BP goals, 1,3 and often this is not enough. There are many reasons for failure to achieve BP targets, including poor adherence to treatment regimens by the patient, inexpertly selected treatment regimens, or conflicting effects of concomitantly administered drugs. [3][4][5] Patients with treatment RHTN typically have other cardiovascular risks, such as obesity, diabetes mellitus (DM), and chronic kidney disease (CKD). Few prospective clinical trials have investigated treatment strategies in patients with treatment RHTN, and most have been largely empirical and uncontrolled. 6 -8 Endothelin receptor antagonists (ERAs) are useful to reduce BP in people with hypertension. Previous studies with the nonselective, sulfonamide-type ERA, bosentan, produced significant reductions in systolic (SBP) and diastolic (DBP) pressures, similar to those observed with an angiotensinconverting enzyme inhibitor in patients with hypertension. 9 Darusentan, a propanoic acid-based endothelin type A-selective receptor antagonist, as a single agent dosed at 100 mg daily, decreased BP by Ϸ11/8 mm Hg, corrected for the placebo response, after 6 weeks in patients with stage 1 or 2 hypertension. 10 Results of a recently published randomized, do...

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Section: Discussionmentioning

confidence: 99%

Divergent Results Using Clinic and Ambulatory Blood Pressures

et al. 2010

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“…[14] A further characteristic of these drugs is their ability to decrease BP without producing sodium retention. [28] The central a 2 -adrenergic agonists have little or no clinical effect on glomerular filtration rate and renal blood flow; however, renal vascular resistance is reduced. Urinary sodium and potassium excretion and body fluid composition are unchanged.…”

Section: Centrally Acting Antihypertensive Drugsmentioning

confidence: 99%

Effects of Antihypertensive Drugs on the Renin-Angiotensin System in Essential Hypertension

Rabbia

Testa

Totaro

et al. 2010

High Blood Pressure & Cardiovascular Prevention

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“…The centrally acting drugs are one of the several differing classes of drug available for antihypertensive therapy. Clonidine is reported to reduce blood pressure without inducing sodium retention (Weber 1989). A growing awareness of the importance of treatment-induced metabolic effects has served to re-awaken interest in centrally acting agents.…”

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Beneficial Effects of Clonidine in Streptozotocin-induced Diabetes and DOCA-hypertensive Rats

Satia

Damani

Goyal

1997

Journal of Pharmacy and Pharmacology

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This investigation was undertaken to study the effects of chronic treatment with clonidine on cardiovascular complications in streptozotocin-induced diabetes and DOCA-hypertensive rats. Injection of streptozotocin induced glucosuria, hyperglycaemia, hypoinsulinaemia, hypothyroidism, hypercholesterolaemia, hypertriglyceridaemia, bradycardia and a decrease in left ventricular developed pressure (LVDP). DOCA by itself did not induce any change in blood-glucose levels in non-diabetic animals. However, in diabetic animals DOCA significantly reduced blood-glucose levels. Treatment of diabetic and diabetic hypertensive animals with clonidine (25 micrograms kg-1 every day for six weeks) significantly prevented diabetes-induced loss of body weight, bradycardia, cardiac hypertrophy and hypothyroidism. It also partially, but significantly, prevented diabetes-induced hyperglycaemia and hypoinsulinaemia in both diabetic and diabetic-hypertensive animals. There was a significant reduction in diabetes-induced elevation of cholesterol and triglyceride levels and an improvement in LVDP at higher filling pressure in diabetic and diabetic hypertensive animals. This investigation shows that chronic treatment with clonidine produces a number of beneficial effects such as prevention of hyperlipidaemia and hypothyroidism and improvement in cardiomyopathy and glycaemic control in diabetic and diabetic hypertensive rats.

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Clinical Pharmacology of Centrally Acting Antihypertensive Agents

Cited by 6 publications

References 27 publications

Divergent Results Using Clinic and Ambulatory Blood Pressures

Divergent Results Using Clinic and Ambulatory Blood Pressures

Effects of Antihypertensive Drugs on the Renin-Angiotensin System in Essential Hypertension

Beneficial Effects of Clonidine in Streptozotocin-induced Diabetes and DOCA-hypertensive Rats

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