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The American Journal of Medicine Sep 1989Rilmenidine is a novel antihypertensive agent related to alpha 2-agonists. Pharmacologic and clinical data concerning efficacy and acceptability of rilmenidine, its... (Review)
Review
Rilmenidine is a novel antihypertensive agent related to alpha 2-agonists. Pharmacologic and clinical data concerning efficacy and acceptability of rilmenidine, its effects on physiologic functions, and hypothesis of mechanism of action are described in this report. The dominant aspect of rilmenidine is the observed dissociation at therapeutic doses between antihypertensive and central effects. In this respect, several findings resulting from fundamental pharmacology, clinical pharmacology, and therapeutics differentiate rilmenidine from clonidine and related drugs. Hypotheses to explain the results observed with rilmenidine involve unknown properties that could counteract with the alpha 2-adrenoceptor-mediated sedation, respective contribution of central and peripheral components to the activity of rilmenidine, and possible contribution of imidazoline receptors.
Topics: Adrenergic alpha-Agonists; Animals; Antihypertensive Agents; Brain; Humans; Hypertension; Oxazoles; Rilmenidine; Wakefulness
PubMed: 2571292
DOI: 10.1016/0002-9343(89)90501-9 -
Drugs of Today (Barcelona, Spain : 1998) Oct 2003Olmesartan is an angiotensin II receptor antagonist indicated for the treatment of essential hypertension. Angiotensin II is an important hormonal effector and... (Review)
Review
Olmesartan is an angiotensin II receptor antagonist indicated for the treatment of essential hypertension. Angiotensin II is an important hormonal effector and end-product of the renin-angiotensin system. When it binds to its endogenous receptor sites, it causes widespread vasoconstriction and a subsequent increase in blood pressure. Olmesartan works by selectively binding to AT(1) against the pathophysiologic events leading to diabetic nephropathy and cardiovascular morbidity/mortality. This end-organ protection is independent of olmesartan's blood pressure lowering properties and is therefore thought to be mediated by different mechanisms. In summary, olmesartan has an efficacy profile superior to other available antihypertensive agents, with a tolerability profile comparable to that of placebo. In addition, the convenience of its once-daily dosing means that olmesartan should be considered not only as an alternative, but also as a first-line treatment for patients with mild to severe essential hypertension. Thus, olmesartan appears to be a very promising new therapy for the treatment of hypertension.
Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Clinical Trials as Topic; Humans; Hypertension; Renin-Angiotensin System
PubMed: 14668930
DOI: 10.1358/dot.2003.39.10.799468 -
Expert Opinion on Pharmacotherapy Dec 2011The modulation of the renin angiotensin aldosterone system (RAAS) is an important pathway in managing high blood pressure, and its overexpression plays a key role in... (Review)
Review
INTRODUCTION
The modulation of the renin angiotensin aldosterone system (RAAS) is an important pathway in managing high blood pressure, and its overexpression plays a key role in target end-organ damage. Telmisartan is an angiotensin II receptor blocker (ARB) with unique pharmacologic properties, including the longest half-life among all ARBs; this leads to a significant and 24-h sustained reduction of blood pressure. Telmisartan has well-known antihypertensive properties, but there is also strong clinical evidence that it reduces left ventricular hypertrophy, arterial stiffness and the recurrence of atrial fibrillation, and confers renoprotection.
AREAS COVERED
This paper reviews telmisartan's pharmacological properties in terms of efficacy for hypertension control and, importantly, focuses on its new therapeutic indications and their clinical implications.
EXPERT OPINION
ONTARGET (ongoing telmisartan alone and in combination with ramipril global endpoint trial) demonstrated, that telmisartan confers cardiovascular protective effects similar to those of ramipril, but with a better tolerability. Moreover, recent investigations focused on the capability of telmisartan to modulate the peroxisome proliferator-activated receptor-gamma (PPAR-γ), an established target in the treatment of insulin resistance, diabetes and metabolic syndrome, whose activation is also correlated to anti-inflammatory and, finally, anti-atherosclerotic properties. Telmisartan shows peculiar features that go beyond blood pressure control. It presents promising and unique protective properties against target end-organ damage, potentially able to open a scenario of new therapeutic approaches to cardiovascular disease.
Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Atrial Fibrillation; Benzimidazoles; Benzoates; Costs and Cost Analysis; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Renin-Angiotensin System; Telmisartan
PubMed: 22077832
DOI: 10.1517/14656566.2011.632367 -
Journal of Human Hypertension Aug 1991Amlodipine is a dihydropyridine calcium antagonist which can be used once daily in hypertension. The pharmacokinetics of the molecule mean that effective blood levels... (Clinical Trial)
Clinical Trial Comparative Study Review
Amlodipine is a dihydropyridine calcium antagonist which can be used once daily in hypertension. The pharmacokinetics of the molecule mean that effective blood levels and hence good control of blood pressure are maintained throughout the dosing interval. Dose-ranging studies have shown the most appropriate starting dose is 5 mg once daily, with simple adjustment to 10 mg if necessary. Comparative studies with other agents have shown amlodipine to have antihypertensive efficacy superior to verapamil and comparable with atenolol, hydrochlorothiazide, captopril or nitrendipine. When used in combination with angiotensin converting enzyme inhibitors, beta-blockers or thiazide diuretics, amlodipine can produce important additional antihypertensive effects. Studies involving long-term use of amlodipine in hypertension indicate that no tolerance appears, and that amlodipine is a well tolerated drug.
Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypertension; Longitudinal Studies; Nifedipine
PubMed: 1834848
DOI: No ID Found -
Cardiovascular Therapeutics Aug 2012The sympathetic nervous system plays a central role in the pathophysiology not only of hypertension and other cardiovascular diseases but also metabolic disorders... (Review)
Review
The sympathetic nervous system plays a central role in the pathophysiology not only of hypertension and other cardiovascular diseases but also metabolic disorders including disturbances of glucose and lipid homeostasis. A centrally acting sympathetic agent is therefore attractive not only for lowering blood pressure, but also intervening with multiple disease processes. Older agents such as clonidine and guanabenz have numerous side effects, including sedation and dry mouth that limit their acceptability to patients. Moxonidine and the related agent rilmenidine have greatly reduced side effects, because they have reduced activity at the α(2) -adrenergic receptors that mediate these undesirable actions. Instead, moxonidine and rilmenidine act primarily through a novel cellular site, termed the I(1) -imidazoline receptor. The molecular biology of the I(1) -imidazoline receptor protein has recently been described, and the cell signaling pathways linked to this protein have been characterized. Moxonidine has unique effects on a number of cell types through this unusual cellular site of action. There are multiple therapeutic implications of these cellular actions, especially for metabolic syndrome and its associated derangements in glucose and lipid metabolism. Finally, the clinical trials that seemed to identify an unfavorable outcome in severe heart failure are dissected and critiqued. We conclude that moxonidine and future successors to this agent could be of great value in treating multiple chronic diseases.
Topics: Animals; Antihypertensive Agents; Blood Pressure; Central Nervous System; Heart Failure; Humans; Hypertension; Imidazoles; Insulin Resistance; Metabolic Syndrome; Sympathetic Nervous System; Sympatholytics; Treatment Outcome
PubMed: 21884003
DOI: 10.1111/j.1755-5922.2011.00268.x -
Current Hypertension Reports Apr 2016The prevalence of resistant hypertension is seemingly much lower than had been reported in early studies. Recent analyses suggest that <5 % of treated hypertensive... (Review)
Review
The prevalence of resistant hypertension is seemingly much lower than had been reported in early studies. Recent analyses suggest that <5 % of treated hypertensive patients remain uncontrolled if fully adherent to an optimized antihypertensive treatment. However, these patients do have increased cardiovascular risk and need effective therapeutic approaches. Drug development is a high-risk, complex, lengthy, and very expensive process. In this article, we discuss the factors that should be considered in the process of developing a new agent for treatment of resistant hypertension.
Topics: Antihypertensive Agents; Cardiovascular Diseases; Drug Resistance; Humans; Hypertension; Prevalence; Prognosis; Risk Factors
PubMed: 26949263
DOI: 10.1007/s11906-016-0634-9 -
Advances in Therapy Jul 2010Despite the availability of a wide range of effective blood pressure (BP)-lowering agents, a substantial proportion of patients with hypertension fail to achieve target... (Review)
Review
Despite the availability of a wide range of effective blood pressure (BP)-lowering agents, a substantial proportion of patients with hypertension fail to achieve target BP levels. The majority of patients with hypertension need a combination of two or more drugs to achieve BP targets and choice of second-line or subsequent-line therapy is an important consideration in hypertension management. Alpha-1-adrenoreceptor antagonists (alpha-blockers) have a BP-lowering effect broadly similar to the other antihypertensive drug classes and are effective as add-on therapy in patients with inadequately controlled hypertension. Alpha-blockers may also have therapeutic benefits that go beyond BP control, including improvements in lipid profile and glucose metabolism, as well as reducing the symptoms of benign prostatic hyperplasia. Urapidil has an alpha-blocking effect but, unlike other alpha-blockers, also has a central sympatholytic effect mediated via stimulation of serotonin 5HT(1A) receptors in the central nervous system. Several studies have suggested that oral urapidil is effective and well tolerated when used as second-line therapy in patients with BP inadequately controlled with other agents. Urapidil has also been shown to improve glucose and lipid metabolism in hypertensive patients with concomitant diabetes and/or hyperlipidemia. Intravenous urapidil is effective in the treatment of hypertensive crises, perioperative hypertension, and pre-eclampsia and may have a potential role in the management of acute stroke. In this review, the use of alpha-blockers in hypertension is discussed, with particular focus on urapidil for the lowering of BP in a variety of clinical settings.
Topics: Adrenergic alpha-Antagonists; Antihypertensive Agents; Drug Therapy, Combination; Humans; Hypertension; Piperazines; Serotonin Receptor Agonists
PubMed: 20652659
DOI: 10.1007/s12325-010-0039-0 -
Expert Opinion on Investigational Drugs Jan 2001Vatanidipine is a novel dihydropyridine (DHP)-type calcium channel blocker with slow-onset pharmacological actions, which are probably due to both its slow uptake into... (Review)
Review
Vatanidipine is a novel dihydropyridine (DHP)-type calcium channel blocker with slow-onset pharmacological actions, which are probably due to both its slow uptake into vascular tissues and resistance in its approach to the calcium channel binding site. Vatanidipine once incorporated into vascular tissues is not easily released, even by repeated washing, thus resulting in a long-lasting action of the agent. A slow-onset and long-lasting hypotensive action was observed in various experimental hypertensive models. Clinical trials using human subjects with essential hypertension indicated that vatanidipine exerts an antihypertensive effect with a slow onset and long duration. In spite of its potent hypotensive effect, the incidence of adverse effects by vatanidipine administration has been reported to be lower than that in cases of nitrendipine. In addition to its vasodilatory effects, vatanidipine efficiently suppressed noradrenaline release from sympathetic nerve endings, thus suggesting this agent exhibits a beneficial effect in the treatment of hypertensive patients, in which the reflex activation of peripheral sympathetic nerves is unfavourable to antihypertensive therapy. In a double-blind study, vatanidipine did not show reflex tachycardia, despite producing a potent and long-lasting hypotensive effect, in contrast to the administration of nitrendipine. In an animal study, vatanidipine exhibited a protective effect against cerebrovascular lesions, through a mechanism independent of its hypotensive effect. In addition, a renoprotective effect was also observed in experimental hypertensive models. In cholesterol-fed rabbits, vatanidipine exerted an anti-atherosclerotic action, which is probably attributable to the inhibitory action of the agent on low-density lipoprotein oxidation. In essential hypertensive patients, the plasma levels of cholesterol and triglyceride decreased after vatanidipine treatment, thus suggesting that this agent may have a therapeutic potential in preventing such vascular diseases as atherosclerosis. Taken together, vatanidipine appears to be a novel and useful antihypertensive agent, which can both prevent target-organ damage and reduce cardiovascular morbidity and mortality.
Topics: Animals; Antihypertensive Agents; Arteriosclerosis; Calcium Channel Blockers; Clinical Trials as Topic; Dihydropyridines; Humans; Hypertension; Nitrendipine
PubMed: 11116287
DOI: 10.1517/13543784.10.1.139 -
Clinical Pharmacy Mar 1988The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of guanfacine hydrochloride are reviewed. Guanfacine lowers blood pressure by... (Review)
Review
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of guanfacine hydrochloride are reviewed. Guanfacine lowers blood pressure by activating CNS alpha adrenoreceptors, which results in sympathetic outflow leading to reduced vascular tone. However, initial hypotensive response to guanfacine may be caused by stimulation of peripheral presynaptic receptors that inhibit sympathetic nerve function. Guanfacine is rapidly and completely absorbed from the gastrointestinal tract and apparently undergoes extensive distribution to all tissues. Steady-state plasma concentrations may be reached in four days. About 30% is excreted renally; the rest is metabolized hepatically. Its long duration of action is related to a slow elimination half-life. In the few controlled clinical trials of guanfacine versus placebo, systolic and diastolic blood pressures were reduced in patients treated with guanfacine; daily dosages of guanfacine 1, 2, and 3 mg (as the hydrochloride salt) were comparable in efficacy. Several large open trials of guanfacine showed blood pressure reductions of about 16% after one year; some patients received other antihypertensive therapy concomitantly. Guanfacine and clonidine appear to have comparable effects in reducing both systolic and diastolic blood pressure when given as monotherapy and as step-2 therapy; data on the comparative blood-pressure-lowering effects of guanfacine and methyldopa are less consistent. Guanfacine's adverse reactions include dry mouth, sedation, and constipation. Adverse effects and reaction to sudden withdrawal of the drug may be less severe with guanfacine than with clonidine. A daily dose of guanfacine 1 mg (as the hydrochloride salt) at bedtime is recommended; 2 or 3 mg, or divided doses, may be given if needed. Once-daily administration and fewer adverse effects may give guanfacine some advantage over other centrally acting antihypertensive agents. Further study is needed to determine whether it will be adequate as first-line therapy.
Topics: Antihypertensive Agents; Guanfacine; Guanidines; Humans; Phenylacetates
PubMed: 3281788
DOI: No ID Found -
Medical Times Feb 1963
Topics: Antihypertensive Agents; Humans; Hydrochlorothiazide
PubMed: 14033279
DOI: No ID Found