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American Journal of Health-system... Jun 2008The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, safety, economic issues, dosage, and place in therapy of nebivolol are reviewed.
PURPOSE
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, safety, economic issues, dosage, and place in therapy of nebivolol are reviewed.
SUMMARY
Nebivolol is a novel, highly selective beta(1)-receptor blocker that causes peripheral vasodilation by increasing the production and release of nitric oxide and decreasing nitric oxide degradation. The nitric oxide-mediated effects of nebivolol lead to decreases in systemic vascular resistance and large artery stiffness and possible reversal of endothelial dysfunction. Clinical studies have shown nebivolol to be at least as effective at lowering blood pressure as other antihypertensive drugs, including other beta-blockers. The most frequent adverse events reported in nebivolol clinical trials were transient headache, dizziness, and tiredness. In a large trial in patients with heart failure, nebivolol was shown to reduce the composite endpoint of mortality and hospitalizations. Nebivolol is highly lipophilic and is rapidly absorbed after oral administration. The nebivolol dose most commonly used in clinical trials for hypertension was 5 mg daily; no significant further decreases in blood pressure were shown with higher doses. The average dose in clinical trials for patients with heart failure was 5-10 mg daily. Dosage adjustments are recommended in elderly patients and patients with severe renal impairment.
CONCLUSION
Nebivolol is a unique, highly selective beta-blocker with vasodilatory properties mediated through the nitric oxide pathway; it may be useful in the treatment of uncomplicated mild-to-moderate essential hypertension and in patients with heart failure.
Topics: Antihypertensive Agents; Benzopyrans; Drug Evaluation; Ethanolamines; Geriatrics; Heart Failure; Humans; Hypertension; Meta-Analysis as Topic; Nebivolol; Placebos; Treatment Outcome
PubMed: 18541682
DOI: 10.2146/ajhp070459 -
The American Journal of Cardiology Mar 1986The pharmacologic data obtained from animal experiments with guanfacine, a novel, centrally acting antihypertensive agent, are reviewed. When given orally, guanfacine... (Comparative Study)
Comparative Study Review
The pharmacologic data obtained from animal experiments with guanfacine, a novel, centrally acting antihypertensive agent, are reviewed. When given orally, guanfacine lowers systemic blood pressure in conscious DOCA-NaCl-hypertensive rats, Grollman rats and spontaneously hypertensive rats in a dose-dependent manner. It is also effective in renal hypertensive cats. Guanfacine reduces blood pressure in cats, rabbits and rats after injection into the lateral cerebral ventricle and in dogs after infusion into the vertebral artery at intravenously ineffective doses. Vagally mediated reflex bradycardia in dogs is enhanced. The preganglionic splanchnic (sympathetic) nerve activity is reduced in cats. In rats, guanfacine reduces the noradrenaline turnover in the brain stem. All these findings indicate a central site of action. Peripheral alpha-adrenoceptor stimulant properties of guanfacine have been demonstrated in various studies. In addition to postsynaptic stimulant effects, presynaptic guanfacine-induced inhibition of sympathetic heart nerve stimulation is antagonized by rauwolscine but not by prazosin, indicating a highly preferential alpha 2-agonistic presynaptic action of the drug. In receptor binding studies using rat cortex membranes and human platelets, guanfacine exhibited a high selectivity for alpha 2 adrenoceptors. Guanfacine has the advantage over other centrally acting antihypertensives of being less sedative and causing no rebound hypertension after discontinuation of treatment. The latter is mainly due to its pharmaco-kinetic properties.
Topics: Animals; Antihypertensive Agents; Blood Pressure; Cats; Dogs; Dopamine; Drug Evaluation, Preclinical; Guanfacine; Guanidines; Guinea Pigs; Heart Rate; Humans; Hypertension; Phenylacetates; Rats; Receptors, Adrenergic, alpha
PubMed: 3006469
DOI: 10.1016/0002-9149(86)90717-4 -
American Journal of Cardiovascular... 2001Structural and functional properties of the arterial wall have been reported to be altered in hypertension, even at early stages of the disease. Morbidity and mortality... (Review)
Review
Structural and functional properties of the arterial wall have been reported to be altered in hypertension, even at early stages of the disease. Morbidity and mortality associated with hypertension are primarily related to arterial damage that may affect one or several organs. Considering the potential implications of arterial assessment in the prevention of cardiovascular disease, evaluation of the arterial effects of antihypertensive agents is recommended by numerous authorities. Among the noninvasive and simple methods to evaluate large arteries, pulse wave velocity (PWV) measurement is widely used as an index of regional arterial stiffness. This method is related to the arterial geometry and wall function, simple and reproducible, and thus, can easily be applied in clinical trials. Several studies performed in various populations showed significant powerful interactions between PWV and cardiovascular risk factors. In addition, aortic PWV was shown to be a forceful marker and predictor of cardiovascular risk in normotensive individuals and patients with hypertension. Furthermore, aortic PWV was shown to be an independent predictor of all-cause mortality in patients with essential hypertension. In comparison with placebo, clinical studies have shown that in short and long term trials, antihypertensive agents improved arterial stiffness (as evidenced by a reduction in PWV) independently of blood pressure reduction. The decrease of PWV was more pronounced with long term treatment than with short term treatment. Whether antihypertensive agents differ in their arterial effects independently of blood pressure changes remains unclear. Pharmacological studies, generally performed in small numbers of patients, indicate that the effects of long term treatment with ACE inhibitors, calcium channel antagonists and some beta-blockers on arterial stiffness are generally similar. The effectiveness of an antihypertensive agent in reducing arterial stiffness may also be influenced by the genetic background of the patient. Recently, the Complior Study has shown the feasibility to assess arterial stiffness in clinical trials involving large populations using an automatic device for measuring PWV. Long term treatment with an ACE inhibitor, perindopril, was associated with a decrease in blood pressure and aortic PWV in patients with essential hypertension. In high risk patients with end-stage renal failure, ACE inhibitors effectively decreased arterial stiffness and had a favorable effect on survival which was independent of changes in blood pressure. The correlation between reversion of arterial stiffness and decrease in cardiovascular morbidity and mortality needs to be confirmed in populations of patients with lower cardiovascular risk.
Topics: Antihypertensive Agents; Arteries; Clinical Trials as Topic; Elasticity; Genotype; Humans; Hypertension; Meta-Analysis as Topic; Pulsatile Flow
PubMed: 14728020
DOI: 10.2165/00129784-200101050-00008 -
The American Journal of Cardiology Jul 1971
Clinical Trial Comparative Study
Topics: Adult; Antihypertensive Agents; Blood Circulation; Blood Volume; Cardiac Output; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Emergencies; Female; Humans; Hypertension; Imidazoles; Kidney; Male; Middle Aged; Parotid Gland; Posture; Saliva; Vascular Resistance
PubMed: 4933458
DOI: 10.1016/0002-9149(71)90037-3 -
Archives of Internal Medicine Apr 1994The relationship of antihypertensive drugs have a long history of association with sexual dysfunction; however, this relationship is poorly documented. There appears to... (Review)
Review
The relationship of antihypertensive drugs have a long history of association with sexual dysfunction; however, this relationship is poorly documented. There appears to be a higher rate of sexual dysfunction in untreated hypertensive men compared with normotensive men. Sexual dysfunction increases with age and is associated with physical and emotional symptoms. There are few studies assessing sexual dysfunction with female and African-American hypertensive patients. Sexual dysfunction is associated with impairment of quality of life and noncompliance. Since group data may hide individual drug effects, baseline data should be collected on all patients before initiating therapy with any antihypertensive agent. Although questionnaires may not provide objective information on sexual dysfunction, the response rate to direct questioning may be less than the response rate on a questionnaire and may be affected by the gender or race of the interviewer. Research protocols using a double-blind, placebo-controlled design should assess sexual dysfunction in men and women in a standardized fashion.
Topics: Age Factors; Antihypertensive Agents; Clinical Trials as Topic; Female; Humans; Male; Patient Compliance; Quality of Life; Sexual Dysfunction, Physiological
PubMed: 8147676
DOI: No ID Found -
Tidsskrift For Den Norske Laegeforening... Oct 1987
Review
Topics: Animals; Antihypertensive Agents; Cod Liver Oil; Fatty Acids, Unsaturated; Fish Oils; Humans
PubMed: 3317987
DOI: No ID Found -
Expert Opinion on Drug Metabolism &... Sep 2009Valsartan/hydrochlorothiazide is a combination of an angiotensin II receptor antagonist and diuretic indicated for hypertensive patients as initial therapy and those not... (Review)
Review
BACKGROUND
Valsartan/hydrochlorothiazide is a combination of an angiotensin II receptor antagonist and diuretic indicated for hypertensive patients as initial therapy and those not controlled on monotherapy.
OBJECTIVE
To evaluate the pharmacokinetic, pharmacodynamic and clinical efficacy of valsartan/hydrochlorothiazide in hypertension therapy and other cardiovascular outcomes.
METHODS
Review of current literature.
RESULTS
Valsartan/hydrochlorothiazide has been shown to be superior to its individual components in randomized controlled studies of patients with moderate-to-severe hypertension and in patients who did not respond to monotherapy. When compared to amlodipine, valsartan/hydrochlorothiazide was shown to have a similar rate of the combined outcome of morbidity and mortality. Valsartan/hydrochlorothiazide has also been studied in specific patient populations, such as diabetics, obese, elderly, black hypertensives and hypertensives with further cardiovascular risk factors, and has been shown to be efficacious in such populations.
CONCLUSION
Valsartan/hydrochlorothiazide has been shown to be an efficacious fixed-dose combination antihypertensive agent that is well tolerated with few side effects.
Topics: Antihypertensive Agents; Clinical Trials as Topic; Drug Combinations; Humans; Hydrochlorothiazide; Hypertension; Tetrazoles; Valine; Valsartan
PubMed: 19689218
DOI: 10.1517/17425250903136730 -
Journal of Cardiovascular Pharmacology 1992L-Arginine, the precursor of endothelium-derived relaxing factor (EDRF)/nitric oxide (NO), was administered intravenously in five patients with essential hypertension,...
L-Arginine, the precursor of endothelium-derived relaxing factor (EDRF)/nitric oxide (NO), was administered intravenously in five patients with essential hypertension, one with renovascular hypertension, one with primary aldosteronism, and one with Cushing's syndrome. During the administration, the mean arterial pressure decreased concomitantly with an elevation of cardiac output and a fall in total peripheral resistance in all cases. Indicators of NO release in vivo such as plasma concentrations of L-citrulline and urinary excretion of nitrite/nitrate increased simultaneously during the administration. These results suggest that exogenous L-arginine can produce a vasodilatory effect via stimulating NO release in hypertensives.
Topics: Antihypertensive Agents; Arginine; Blood Pressure; Cardiac Output; Citrulline; Cushing Syndrome; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renovascular; Injections, Intravenous; Nitrates; Nitrites
PubMed: 1282968
DOI: 10.1097/00005344-199204002-00055 -
American Journal of Health-system... Aug 2009Intravenous antihypertensive agents for the treatment of hypertensive emergencies are reviewed. (Review)
Review
PURPOSE
Intravenous antihypertensive agents for the treatment of hypertensive emergencies are reviewed.
SUMMARY
An estimated 500,000 people in the United States experience a hypertensive crisis annually. Hypertensive emergency is associated with significant morbidity in the form of end-organ damage. Rapid controlled reduction of blood pressure (BP) may be necessary to prevent or minimize end-organ damage. I.V. antihypertensive agents available for the treatment of hypertensive emergencies are, in general, characterized by a short onset and offset of action and predictable responses during dosage adjustments to reach BP goals, without excessive adjustment or extreme fluctuations in BP. Nicardipine, nitroprusside, fenoldopam, nitroglycerin, enalaprilat, hydralazine, labetalol, esmolol, and phentolamine are i.v. antihypertensive agents recommended for use in hypertensive emergency by the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Since the publication of these recommendations, another i.v. antihypertensive agent, clevidipine, became commercially available. The selection of a specific agent should be based on the agent's pharmacology and patient-specific factors, such as comorbidity and the presence of end-organ damage.
CONCLUSION
The rapid recognition and initiation of therapy are key to minimizing end-organ damage in patients with hypertensive emergency. Tailoring drug selection according to individual patient characteristics can optimize the management and potential outcomes of patients with hypertensive emergency.
Topics: Antihypertensive Agents; Emergency Medical Services; Humans; Hypertension; Infusions, Intravenous
PubMed: 19635770
DOI: 10.2146/ajhp080348.p1 -
American Journal of Health-system... Aug 2009Intravenous antihypertensive agents for the treatment of hypertensive emergencies are reviewed. (Review)
Review
PURPOSE
Intravenous antihypertensive agents for the treatment of hypertensive emergencies are reviewed.
SUMMARY
An estimated 500,000 people in the United States experience a hypertensive crisis annually. Hypertensive emergency is associated with significant morbidity in the form of end-organ damage. Rapid controlled reduction of blood pressure (BP) may be necessary to prevent or minimize end-organ damage. I.V. antihypertensive agents available for the treatment of hypertensive emergencies are, in general, characterized by a short onset and offset of action and predictable responses during dosage adjustments to reach BP goals, without excessive adjustment or extreme fluctuations in BP. Nicardipine, nitroprusside, fenoldopam, nitroglycerin, enalaprilat, hydralazine, labetalol, esmolol, and phentolamine are i.v. antihypertensive agents recommended for use in hypertensive emergency by the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Since the publication of these recommendations, another i.v. antihypertensive agent, clevidipine, became commercially available. The selection of a specific agent should be based on the agent's pharmacology and patient-specific factors, such as comorbidity and the presence of end-organ damage.
CONCLUSION
The rapid recognition and initiation of therapy are key to minimizing end-organ damage in patients with hypertensive emergency. Tailoring drug selection according to individual patient characteristics can optimize the management and potential outcomes of patients with hypertensive emergency.
Topics: Antihypertensive Agents; Emergency Treatment; Humans; Hypertension; Infusions, Intravenous; Practice Guidelines as Topic
PubMed: 19667001
DOI: 10.2146/ajhp080348.p2