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Vascular Health and Risk Management 2012β-blockers are effective antihypertensive agents and, together with diuretics, have been the cornerstone of pioneering studies showing their benefits on cardiovascular... (Review)
Review
β-blockers are effective antihypertensive agents and, together with diuretics, have been the cornerstone of pioneering studies showing their benefits on cardiovascular morbidity and mortality as a consequence of blood pressure reduction in patients with hypertension. However, evidence from recent meta-analyses have demonstrated no benefit afforded by atenolol compared with placebo in risk of mortality, myocardial infarction, or stroke, and a higher risk of mortality and stroke with atenolol/propranolol compared with other antihypertensive drug classes. Thus, the effect of these agents on cardiovascular morbidity and mortality in hypertensive patients, especially their use in uncomplicated hypertension, has remained largely controversial. However, it is recognized that the clinical studies used in these meta-analyses were mainly based on the older second-generation β-blockers, such as atenolol and metoprolol. Actually, considerable heterogeneity in, eg, pharmacokinetic, pharmacological, and physicochemical properties exists across the different classes of β-blockers, particularly between the second-generation and newer third-generation agents. Carvedilol is a vasodilating noncardioselective third-generation β-blocker, without the negative hemodynamic and metabolic effects of traditional β-blockers, which can be used as a cardioprotective agent. Compared with conventional β-blockers, carvedilol maintains cardiac output, has a reduced prolonged effect on heart rate, and reduces blood pressure by decreasing vascular resistance. Studies have also shown that carvedilol exhibits favorable effects on metabolic parameters, eg, glycemic control, insulin sensitivity, and lipid metabolism, suggesting that it could be considered in the treatment of patients with metabolic syndrome or diabetes. The present report provides an overview of the main clinical studies concerning carvedilol administered as either monotherapy or in combination with another antihypertensive or more frequently a diuretic agent, with particular focus on the additional benefits beyond blood pressure reduction.
Topics: Adrenergic beta-Antagonists; Animals; Antihypertensive Agents; Blood Pressure; Carbazoles; Carvedilol; Comorbidity; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Hypertension; Patient Selection; Propanolamines; Risk Assessment; Treatment Outcome; Vasodilator Agents
PubMed: 22661898
DOI: 10.2147/VHRM.S31578 -
Canadian Journal of Physiology and... Jul 2022Endothelin has emerged as a target for therapeutic intervention in systemic hypertension. As a vasoconstrictor, comitogenic agent, linking pulse pressure and vascular... (Review)
Review
Endothelin has emerged as a target for therapeutic intervention in systemic hypertension. As a vasoconstrictor, comitogenic agent, linking pulse pressure and vascular remodeling, and mediator of aldosterone and catecholamine release, endothelin is a key player in hypertension and end-organ damage. In 10%-20% of the hypertensive population, the high blood pressure is resistant to administration of antihypertensive drugs of different classes in combination. Because endothelin is not targeted by the current antihypertensive drugs, this may suggest that this resistance is due, in part at least, to a dependence on endothelin. This hypothesis is supported by the observation that this form of hypertension is often salt-sensitive, and that the endothelin system is stimulated by salt. In addition, the endothelin system is activated in subjects at risk of developing resistant hypertension, such as African Americans or patients with obesity or obstructive sleep apnea. Aprocitentan is an investigational, novel, potent, dual endothelin receptor antagonist (ERA) currently in phase 3 development for the treatment of difficult-to-treat hypertension. This article discusses the research that underpinned the discovery of this ERA and the choice of its first clinical indication for patients with forms of hypertension that cannot be well controlled with classical antihypertensive drugs.
Topics: Antihypertensive Agents; Endothelin Receptor Antagonists; Endothelin-1; Endothelins; Humans; Hypertension; Pyrimidines; Receptor, Endothelin A; Sulfonamides
PubMed: 35245103
DOI: 10.1139/cjpp-2022-0010 -
European Respiratory Review : An... Mar 2017Chronic thromboembolic pulmonary hypertension (CTEPH) results from incomplete resolution of acute pulmonary emboli, organised into fibrotic material that obstructs large... (Review)
Review
Chronic thromboembolic pulmonary hypertension (CTEPH) results from incomplete resolution of acute pulmonary emboli, organised into fibrotic material that obstructs large pulmonary arteries, and distal small-vessel arteriopathy. Pulmonary endarterectomy (PEA) is the treatment of choice for eligible patients with CTEPH; in expert centres, PEA has low in-hospital mortality rates and excellent long-term survival. Supportive medical therapy consists of lifelong anticoagulation plus diuretics and oxygen, as needed.An important recent advance in medical therapy for CTEPH is the arrival of medical therapies for patients with inoperable disease or persistent/recurrent pulmonary hypertension after PEA. The soluble guanylate cyclase stimulator riociguat is licensed for the treatment of CTEPH in patients with inoperable disease or with recurrent/persistent pulmonary hypertension after PEA. Clinical trials of this agent have shown improvements in patients' haemodynamics and exercise capacity. Phosphodiesterase-5 inhibitors, endothelin receptor antagonists and prostanoids have been used in the treatment of CTEPH, but evidence of benefit is limited. Challenges in the future development of medical therapy for CTEPH include better understanding of the underlying pathology, end-points to monitor the condition's progress, and the optimisation of pulmonary arterial hypertension therapies in relation to diverse patient characteristics and emerging options such as balloon pulmonary angioplasty.
Topics: Anticoagulants; Antihypertensive Agents; Chronic Disease; Diuretics; Humans; Hypertension, Pulmonary; Oxygen Inhalation Therapy; Pulmonary Embolism; Recurrence; Risk Factors; Treatment Outcome
PubMed: 28356404
DOI: 10.1183/16000617.0107-2016 -
Current Pharmaceutical Design 2015Drug discovery and development is a high-risk enterprise that requires significant investments in capital, time and scientific expertise. The studies of xenobiotic... (Review)
Review
Drug discovery and development is a high-risk enterprise that requires significant investments in capital, time and scientific expertise. The studies of xenobiotic metabolism remain as one of the main topics in the research and development of drugs, cosmetics and nutritional supplements. Antihypertensive drugs are used for the treatment of high blood pressure, which is one the most frequent symptoms of the patients that undergo cardiovascular diseases such as myocardial infraction and strokes. In current cardiovascular disease pharmacology, four drug clusters - Angiotensin Converting Enzyme Inhibitors, Beta-Blockers, Calcium Channel Blockers and Diuretics - cover the major therapeutic characteristics of the most antihypertensive drugs. The pharmacokinetic and specifically the metabolic profile of the antihypertensive agents are intensively studied because of the broad inter-individual variability on plasma concentrations and the diversity on the efficacy response especially due to the P450 dependent metabolic status they present. Several computational methods have been developed with the aim to: (i) model and better understand the human drug metabolism; and (ii) enhance the experimental investigation of the metabolism of small xenobiotic molecules. The main predictive tools these methods employ are rule-based approaches, quantitative structure metabolism/activity relationships and docking approaches. This review paper provides detailed metabolic profiles of the major clusters of antihypertensive agents, including their metabolites and their metabolizing enzymes, and it also provides specific information concerning the computational approaches that have been used to predict the metabolic profile of several antihypertensive drugs.
Topics: Antihypertensive Agents; Computational Biology; Humans; Hypertension
PubMed: 25341854
DOI: 10.2174/1381612820666141024151119 -
The Canadian Journal of Cardiology May 2022Resistant hypertension is associated with cardiovascular morbidity and mortality. The objective of this study was to estimate the prevalence of apparent...
BACKGROUND
Resistant hypertension is associated with cardiovascular morbidity and mortality. The objective of this study was to estimate the prevalence of apparent treatment-resistant hypertension in Canadian adults and examine the characteristics of those affected.
METHODS
A nationally representative cross-sectional study was conducted with the use of Canadian Health Measures Survey (2007-2017) data. The frequency of respondents with uncontrolled blood pressure despite 3 or more antihypertensive medications of different drug classes (and at least 1 agent being a diuretic), or treatment with 4 or more agents regardless of blood pressure, was determined.
RESULTS
A total of 245,700 people were identified to have apparent treatment-resistant hypertension, representing 5.3% (95% confidence interval [CI] 4.5%-6.2%) of adults treated for hypertension in Canada. Respondents who had uncontrolled blood pressure with 3 or more antihypertensive drugs were more likely women (55.8%, 95% CI 41.1%-70.4%), 70 years of age or older (45.3% 95% CI 32.8%-57.9%), and overweight or obese (84.2%, 95% CI 72.3%-96.1%). Respondents with apparent treatment-resistant hypertension also had a high likelihood of chronic kidney disease (36.0%, 95% CI 21.4%-50.6%), diabetes (35.2%, 95% CI 21.7%-48.7%), dyslipidemia (68.0%, 95% CI 55.2%-80.8%), and history of heart attack (9.9%, 95% CI 4.8%-15.1%) or stroke (7.1%, 95% CI 0-14.4%).
CONCLUSIONS
Despite being prescribed at least 3 antihypertensive drugs, a considerable proportion of Canadians, especially women, have difficulty achieving blood pressure control, predisposing them to a higher risk of cardiovascular complications and death.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Canada; Cross-Sectional Studies; Female; Humans; Hypertension
PubMed: 35122938
DOI: 10.1016/j.cjca.2022.01.029 -
PloS One 2020Hypertension is an important risk factor for nonalcoholic steatohepatitis. We have previously demonstrated that hypertensive rats fed a high fat and cholesterol (HFC)...
Hypertension is an important risk factor for nonalcoholic steatohepatitis. We have previously demonstrated that hypertensive rats fed a high fat and cholesterol (HFC) diet incurred a more severe hepatic inflammatory response and fibrosis. Here we investigated the role of hypertension in NASH by comparing HFC-induced hepatic fibrogenesis between spontaneously hypertensive rats (SHRs) and their normotensive Wistar Kyoto counterpart. Compared to the counterpart, the HFC diet led to stronger aggregation of CD68-positive macrophages in SHRs. HFC feeding also resulted in significantly higher upregulation of the fibrosis-related gene alpha-smooth muscle actin in SHR. The HFC diet induced higher overexpression of serum tissue inhibitor of metalloproteinase-1 (TIMP1) and greater suppression of matrix metalloproteinase-2 (MMP2):TIMP1, MMP8:TIMP1, and MMP9:TIMP1 ratios, as a proxy of the activities of these MMPs in SHR. Administration of the antihypertensive agent hydralazine to SHRs significantly ameliorated HFC-induced liver fibrosis; it suppressed the aggregation of CD68-positive macrophages and the upregulation of platelet-derived growth factor receptor beta, and collagen, type 1, alpha-1 chain. In conclusion, a hypertensive environment exacerbated the hepatic fibrogenetic effects of the HFC diet; while the effects were partially reversed by the antihypertensive agent hydralazine. Our data suggest that antihypertensive drugs hold promise for treating NASH exacerbated by hypertension.
Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antihypertensive Agents; Blood Pressure; Body Weight; Cholesterol, Dietary; Cytokines; Diet, High-Fat; Disease Progression; Extracellular Matrix; Gene Expression Regulation; Hydralazine; Hypertension; Liver; Liver Cirrhosis; Macrophages; Male; Matrix Metalloproteinases; Models, Biological; Non-alcoholic Fatty Liver Disease; Organ Size; Rats, Inbred SHR; Rats, Inbred WKY; Tissue Inhibitor of Metalloproteinase-1
PubMed: 33315911
DOI: 10.1371/journal.pone.0243846 -
Acta Medica Academica Dec 2021The aim of this study is to evaluate and present the evidence so far, regarding fetal outcomes after in utero exposure to antihypertensive medication. Hypertensive... (Review)
Review
The aim of this study is to evaluate and present the evidence so far, regarding fetal outcomes after in utero exposure to antihypertensive medication. Hypertensive disorders during pregnancy constitute a significant risk factor for maternal and fetal outcomes, necessitating antihypertensive treatment. However, current data concerning the safety of in utero exposure to antihypertensive medication are controversial. While some studies recommend the administration of certain agents, others underline the possible adverse effects on fetal development. This review aims to summarize the outcomes of studies published during the last decade, referring to first trimester in utero exposure to antihypertensive agents. In general, a-methyldopa, β-blockers and calcium channel blockers are the first or second treatment line for hypertension during pregnancy. However, ACEIs, ARBs and diuretics are mostly contraindicated, as the potential risk outweighs the benefits of their administration. Additionally, several drugs should be avoided, due to the lack of data regarding their safety. CONCLUSION: As current studies are restricted for ethical reasons, there is a significant lack of evidence concerning diverse antihypertensive agent use. In utero exposure to antihypertensive medication needs to be carefully evaluated and supported by further research.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Female; Humans; Hypertension; Pregnancy; Pregnancy Trimester, First
PubMed: 35164513
DOI: 10.5644/ama2006-124.356 -
Dialogues in Clinical Neuroscience 2011The literature is filled with reports that link medications with the onset or progression of depression. Because depression is so common in patients with medical... (Review)
Review
The literature is filled with reports that link medications with the onset or progression of depression. Because depression is so common in patients with medical illness, assessing whether a medication has in fact caused depression, or whether the relationship is coincidental, can be challenging. In this article, we review the literature on the association between medications and depression. For most agents, there are case reports or small studies linking the medication with the onset of depression, but more rigorous prospective studies are either lacking or found no association between the agent and depression. However, several medications, (eg, barbiturates, vigabatrin, topiramate, flunarizine, corticosteroids, mefloquine, efavirenz, and interferon-alpha) do appear to cause depression in some patients and should be used with caution in patients at risk for depression.
Topics: Anti-Infective Agents; Antihypertensive Agents; Antineoplastic Agents; Cardiovascular Agents; Depression; Humans
PubMed: 21485751
DOI: 10.31887/DCNS.2011.13.1/ccelano -
British Medical Journal Aug 1971Sodium nitroprusside is a readily available, powerful hypotensive agent. It was administered intravenously in four cases when all other available hypotensive agents had...
Sodium nitroprusside is a readily available, powerful hypotensive agent. It was administered intravenously in four cases when all other available hypotensive agents had failed, and blood pressure was controlled promptly and with no side effects. This is a valuable drug and deserves wider use.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Ferricyanides; Humans; Hypertension; Hypertension, Renal; Injections, Intravenous; Male; Middle Aged
PubMed: 5566620
DOI: 10.1136/bmj.3.5771.407 -
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