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Advances in Chronic Kidney Disease Mar 2016Hypertension is a multifactorial condition with diverse physiological systems contributing to its pathogenesis. Individuals exhibit significant variation in their... (Review)
Review
Hypertension is a multifactorial condition with diverse physiological systems contributing to its pathogenesis. Individuals exhibit significant variation in their response to antihypertensive agents. Traditional markers, such as age, gender, diet, plasma renin level, and ethnicity, aid in drug selection. However, this review explores the contribution of genetics to facilitate antihypertensive agent selection and predict treatment efficacy. The findings, reproducibility, and limitations of published studies are examined, with emphasis placed on candidate genetic variants affecting drug metabolism, the renin-angiotensin system, adrenergic signalling, and renal sodium reabsorption. Single-nucleotide polymorphisms identified and replicated in unbiased genome-wide association studies of hypertension treatment are reviewed to illustrate the evolving understanding of the disease's complex and polygenic pathophysiology. Implementation efforts at academic centers seek to overcome barriers to the broad adoption of pharmacogenomics in the treatment of hypertension. The level of evidence required to support the implementation of pharmacogenomics in clinical practice is considered.
Topics: Antihypertensive Agents; Cytochrome P-450 Enzyme System; Genome-Wide Association Study; Humans; Hypertension; Pharmacogenetics; Polymorphism, Genetic; Receptors, Adrenergic, beta; Renin-Angiotensin System; Signal Transduction; Sodium
PubMed: 26979148
DOI: 10.1053/j.ackd.2016.02.003 -
Journal of Cardiovascular Pharmacology Aug 2011Traditionally, antihypertensive medications were used in few children or adolescents, usually just those with underlying renal or other organ system disease. However,... (Review)
Review
Traditionally, antihypertensive medications were used in few children or adolescents, usually just those with underlying renal or other organ system disease. However, with recent data suggesting that the incidence of primary hypertension may be increasing in the young, it is possible that more children and adolescents will be prescribed antihypertensive agents. This article will review currently available pediatric data on the use of calcium channel blockers, agents affecting the renin-angiotensin-aldosterone system and other classes of antihypertensive medications in children, highlighting appropriate indications and safety considerations. Guidelines for use of antihypertensive medications, including choice of initial agent and how to prescribe appropriately, will be presented.
Topics: Adolescent; Antihypertensive Agents; Child; Drug Administration Schedule; Humans; Hypertension; Practice Guidelines as Topic
PubMed: 21242810
DOI: 10.1097/FJC.0b013e31820d1b89 -
Nephrology, Dialysis, Transplantation :... Apr 2006
Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Hypertension; Kidney Diseases
PubMed: 16384819
DOI: 10.1093/ndt/gfk025 -
Current Vascular Pharmacology Nov 2010Antihypertensive agents exert different effects on insulin sensitivity, lipids and haemostasis. However, most studies assessing these effects were small and short-term... (Review)
Review
Antihypertensive agents exert different effects on insulin sensitivity, lipids and haemostasis. However, most studies assessing these effects were small and short-term yielding conflicting results. Moreover, it has not been established whether the impact of antihypertensive drugs on insulin sensitivity, lipids, thrombosis and fibrinolysis adds to or attenuates vascular risk reduction. On the other hand, new onset type 2 diabetes mellitus (T2DM) appears to be more frequent in patients treated with β-blockers and diuretics, whereas angiotensin converting enzyme inhibitors and angiotensin receptor blockers might reduce the risk for T2DM and calcium channel blockers have a neutral effect. Therefore, the risk of developing T2DM should be considered when selecting an antihypertensive agent. This review discusses the differential effects of antihypertensive drugs on insulin sensitivity, lipids and haemostasis and considers their association with vascular risk.
Topics: Antihypertensive Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Female; Hemostasis; Humans; Hypertension; Insulin Resistance; Lipid Metabolism; Male; Prognosis
PubMed: 20626344
DOI: 10.2174/157016110793563906 -
Vascular Pharmacology Dec 2021The concurrent administration of statins and antihypertensive agents has been associated with improved cardiovascular outcomes, although the optimal fixed-dose... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The concurrent administration of statins and antihypertensive agents has been associated with improved cardiovascular outcomes, although the optimal fixed-dose combination remains unclear. This meta-analysis aims to compare the blood pressure and lipid-lowering effects of various statin and antihypertensive drug combinations.
METHODS
PubMed, Scopus, Web of Science, CENTRAL and Clinicaltrials.gov were systematically searched from inception to 20 March 2021. Randomized controlled trials evaluating the effects of statin-antihypertensive agent combinations on systolic blood pressure or serum lipids were held eligible. A random-effects frequentist model was applied to provide estimates of mean difference of percentage change.
RESULTS
Overall, 18 studies were included, comprising 4450 patients. Compared to statin monotherapy no significant difference in the percentage change of low-density lipoprotein cholesterol was achieved by adding any antihypertensive agent. Compared to amlodipine monotherapy, the addition of moderate-intensity statin resulted in a significantly greater percentage reduction of systolic blood pressure (-2.22%, 95% confidence intervals: [-3.82 to -0.62]). Combined high-intensity statin and amlodipine lead to significant increase of high-density lipoprotein cholesterol (8.34%, 95% confidence intervals: [0.73 to 15.95]), while effective triglyceride reduction was achieved by adding amlodipine and telmisartan to high-intensity statin (-14.68%, 95% confidence intervals: [-28.48 to -0.89]). No significant difference of adverse effects was observed.
CONCLUSION
The present network meta-analysis suggests that the administration of fixed-dose combinations of statins and antihypertensive agents is safe and effective in reducing blood pressure and serum lipids. The optimal dosing strategy to prevent cardiovascular events remains to be determined.
Topics: Antihypertensive Agents; Blood Pressure; Drug Combinations; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 34343694
DOI: 10.1016/j.vph.2021.106900 -
Journal of Clinical Pharmacology Mar 1990Parenteral antihypertensive agents are useful in those clinical situations where rapid reduction of blood pressure is necessary or where treatment with oral... (Review)
Review
Parenteral antihypertensive agents are useful in those clinical situations where rapid reduction of blood pressure is necessary or where treatment with oral antihypertensive medications is not feasible. Given the diverse selection of parenteral antihypertensive drugs now available, therapy can be individualized. The presence of concurrent diseases will often influence the decision-making process regarding choice of an agent. Complications of parenteral antihypertensive therapy can arise from the intrinsic properties of the various drugs or the development of severe hypotension. Gradual lowering of blood pressure, in conjunction with careful clinical evaluation, will minimize the risks of acute parenteral antihypertensive therapy. Given that parenteral antihypertensive therapy often needs to be replaced by oral therapy, those drugs that can be used both parenterally and orally may have an advantage.
Topics: Antihypertensive Agents; Humans; Injections
PubMed: 2179288
DOI: 10.1002/j.1552-4604.1990.tb03463.x -
Journal of Human Hypertension Aug 1997Moxonidine is a centrally acting antihypertensive. Its action is mediated by imidazoline I1 receptors located in the rostral ventro-lateral medulla (RVLM). Animal... (Comparative Study)
Comparative Study Review
Moxonidine is a centrally acting antihypertensive. Its action is mediated by imidazoline I1 receptors located in the rostral ventro-lateral medulla (RVLM). Animal experiments show much smaller amounts are required to reduce blood pressure (BP) when it is given intracisternally, or injected directly into the RVLM, compared to intravenous dose. The antihypertensive action of microinjection of moxonidine into the RVLM in the spontaneously hypertensive rat (SHR) is abolished by pretreatment with imidazoline I1 blockade from efaroxan, but alpha(2) blockade from SKF 86466 has much less effect. Similarly the fall of BP in the SHR from intravenous moxonidine is reversed by the microinjection of efaroxan into the RVLM. Receptor binding studies demonstrate that moxonidine binds with an affinity for the imidazoline I1 receptor that is thirty-three times more effective than is alpha(2) receptor binding, while for clonidine the difference is only four times. Moxonidine reduces adrenaline, noradrenaline and renin levels in man, a finding consistent with central inhibition of sympathetic tone. Acute haemodynamic studies indicate that moxonidine results in a fall of BP due to a decline in systemic vascular resistance, while the heart rate, cardiac output, stroke volume and pulmonary artery pressures are not affected. Left ventricular end systolic and diastolic volumes are reduced. Left ventricular hypertrophy has been found to regress after 6 months treatment with moxonidine. After oral administration Tmax is about 1 h, bioavailability approaches 90%. Moxonidine is mostly excreted unchanged, biotransformation is unimportant. The T1/2 is 2.5 h, which is prolonged by renal insufficiency. However, suggesting possible retention in the central nervous system (CNS), the antihypertensive effect lasts longer than would be expected from the half-life, as moxonidine is suitable for once daily administration. Moxonidine is an effective antihypertensive agent. It has been compared with representatives from each important class of antihypertensive drugs, with clonidine, diuretics, both alpha- and beta-blocking drugs, calcium antagonists and ACE inhibitors. BP control has been similar with moxonidine and these other agents. The side effect profile of moxonidine is favourable, its lack of effect on central alpha(2) receptors is important in this regard.
Topics: Animals; Antihypertensive Agents; Catecholamines; Female; Hemodynamics; Humans; Hypertension; Imidazoles; Imidazoline Receptors; Male; Medulla Oblongata; Rats; Receptors, Adrenergic; Receptors, Drug; Safety; Sympathetic Nervous System
PubMed: 9321737
DOI: No ID Found -
Journal of the American Society of... Oct 2005The objective of this study was to evaluate the comparative effects of antihypertensive agents in patients with diabetes and normoalbuminuria. Randomized, controlled... (Review)
Review
The objective of this study was to evaluate the comparative effects of antihypertensive agents in patients with diabetes and normoalbuminuria. Randomized, controlled trials that compared any antihypertensive agent with placebo or another agent in hypertensive or normotensive patients with diabetes and normoalbuminuria (albumin excretion rate <30 mg/d) were identified on Medline, in Embase, on the Cochrane Controlled Trials Register, in conference proceedings, and by contacting investigators. Two authors independently extracted data on renal outcomes and other patient-relevant outcomes (e.g., mortality, serious cardiovascular events) and assessed quality of trials. Analysis was by a random-effects model, and results were expressed as relative risk (RR) and 95% confidence intervals (CI). Sixteen trials (7603 patients) were identified, six of angiotensin-converting enzyme inhibitors (ACEi) versus placebo, six of ACEi versus calcium antagonists, one of ACEi versus calcium antagonists or combined ACEi and calcium antagonist, and three of ACEi versus other agents. Compared with placebo, ACEi significantly reduced the development of microalbuminuria (six trials, 3840 patients; RR 0.60; 95% CI 0.43 to 0.84) but not doubling of creatinine (three trials, 2683 patients; RR 0.81; 95% CI 0.24 to 2.71) or all-cause mortality (four trials, 3284 patients; RR 0.81; 95% CI 0.64 to 1.03). Compared with calcium antagonists, ACEi significantly reduced progression to microalbuminuria (four trials, 1210 patients; RR 0.58; 95% CI 0.40 to 0.84). A significant reduction in the risk for developing microalbuminuria in normoalbuminuric patients with diabetes has been demonstrated for ACEi only. It seems that the effect of ACEi is independent of baseline BP, renal function, and type of diabetes, but data are too sparse to be confident that these are not important effect modifiers, and an individual patient data meta-analysis is required.
Topics: Antihypertensive Agents; Diabetic Nephropathies; Humans; Randomized Controlled Trials as Topic
PubMed: 16135776
DOI: 10.1681/ASN.2004080634 -
Blood Pressure Aug 2011Despite the proven efficacy of current strategies for cardiovascular (CV) risk reduction, a considerable gap remains between the risk reductions achieved in clinical... (Review)
Review
Despite the proven efficacy of current strategies for cardiovascular (CV) risk reduction, a considerable gap remains between the risk reductions achieved in clinical trials and those seen in clinical practice. A major reason for this is poor compliance to medication, which has been extensively documented for antihypertensive therapy. Low adherence results in suboptimal blood pressure control, which is associated with adverse CV outcomes and increased treatment costs. Adverse effects of medication are an important cause of diminished adherence. Angiotensin II receptor blockers (ARBs) may offer better long-term tolerability than other classes of antihypertensive agent, and this is likely to be a major factor in the high levels of adherence and persistence seen with these agents. This could have implications for CV protection, as confirmed by the results of recent clinical trials. Thus, ARBs should be considered as an alternative to angiotensin-converting enzyme inhibitors in patients at risk of low adherence.
Topics: Antihypertensive Agents; Cardiovascular Diseases; Female; Humans; Hypertension; Male; Medication Adherence
PubMed: 21299436
DOI: 10.3109/08037051.2011.557902 -
Developmental Pharmacology and... 1989A consistent body of evidence indicates that in the preterm and full-term newborn drug disposition is reduced when compared to that of infants, grown-up children, and... (Review)
Review
A consistent body of evidence indicates that in the preterm and full-term newborn drug disposition is reduced when compared to that of infants, grown-up children, and adults. Newborns are rarely treated directly with antihypertensive agents; however they can be exposed to the action of various antihypertensive drugs in utero and during their first week of extrauterine life in the case of hypertensive mothers treated through pregnancy. In such cases, the persistence of the antihypertensive agent during the first days of life may have important consequences on neonatal haemodynamics and on the function and the maturation of vital organs such as lungs and kidneys. The available information on the placental transfer and neonatal pharmacokinetics of alpha-methyldopa, clonidine, acebutolol, atenolol, betaxolol, metoprolol, propanolol, oxprenolol, and latetalol, are reviewed. Each product has its own pharmacokinetic characteristics which should influence, depending on the clinical situation, the therapeutic choice. In the presence of comparable efficacy, preference should be given to compounds with high bioavailability, eliminated mainly via metabolic degradation, with no active metabolites. In all cases, treatment should be discontinued 8-12 h before delivery.
Topics: Antihypertensive Agents; Humans; Infant, Newborn
PubMed: 2693002
DOI: 10.1159/000457604