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Heart Disease (Hagerstown, Md.) 2000The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension report has recommended long-acting, once-daily drugs... (Review)
Review
The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension report has recommended long-acting, once-daily drugs as preferred therapy for the management of hypertension. The duration of action of an antihypertensive agent can be assessed in several ways. The decrease in clinical blood pressure at the end of the dosing interval has traditionally been the method for determining antihypertensive efficacy. However, this approach does not provide information about a drug's effects over the remainder of the 24-hour dosing interval. The trough-to-peak ratio has been proposed as an arithmetic index of a compound's maximum and minimum antihypertensive effects. This ratio can be obtained from multiple readings in an office setting or using data from 24-hour ambulatory blood-pressure monitoring. A simplified approach has been to compare a single office reading at the time of a drug's known maximum antihypertensive effect (peak) with the reduction in blood pressure at 24 hours (trough). Office readings have also been used to show that the same dose of a drug given once daily versus twice daily results in a similar trough blood pressure, confirming that once-daily therapy is appropriate. The 24-hour ambulatory blood pressure can be used to determine mean changes in daytime, evening, and night-time blood pressure to demonstrate the antihypertensive profile over the entire dosing interval. Finally, the finding of a persistent reduction in ambulatory blood pressure following substitution of placebo for an antihypertensive drug during chronic therapy (missed-dose technique) suggests that a compound decreases blood pressure for 48 hours or longer. Thus, it should be possible to demonstrate the effectiveness of once-daily antihypertensive therapy using one or more of the aforementioned methods.
Topics: Antihypertensive Agents; Blood Pressure Determination; Costs and Cost Analysis; Drug Administration Schedule; Humans; Hypertension; Patient Compliance
PubMed: 11728257
DOI: No ID Found -
American Journal of Hypertension Mar 2001Oxidized low-density lipoprotein (ox-LDL) is well known to play an important role in atherogenesis through the recruitment of monocytes into vessel walls and the...
Oxidized low-density lipoprotein (ox-LDL) is well known to play an important role in atherogenesis through the recruitment of monocytes into vessel walls and the deposition of cholesterol ester in the macrophages, which leads to the formation of lipid-rich plaque. It was assumed that only trace amounts of ox-LDL were present in plasma because the half-life of ox-LDL was only a few minutes. Recently, through the use of a monoclonal antibody against ox-LDL, a quantitative method to measure serum ox-LDL concentration has been developed. Metabolites of doxazosin, an alpha1-adrenergic antihypertensive agent, have been reported to inhibit oxidation of LDL in vitro. In this study, we investigated the in vivo effect of doxazosin on LDL oxidation using this new method to measure serum ox-LDL concentration. After the administration of doxazosin for 1 to 2 months, serum concentration of ox-LDL decreased significantly (P < .05). Although the reduction of ox-LDL concentration does not strictly indicate doxazosin's antiatherosclerotic effect, it may constitute one of doxazosin's additional weapons beside lowering blood pressure and serum lipid values in the prevention of atherosclerosis.
Topics: Adrenergic alpha-Antagonists; Anticholesteremic Agents; Antihypertensive Agents; Doxazosin; Female; Humans; Lipoproteins, LDL; Male; Oxidation-Reduction
PubMed: 11281239
DOI: 10.1016/s0895-7061(00)01263-2 -
American Journal of Health-system... Apr 2000The mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, and adverse effects of candesartan cilexetil are reviewed. Candesartan is an angiotensin... (Review)
Review
The mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, and adverse effects of candesartan cilexetil are reviewed. Candesartan is an angiotensin II-receptor blocker (ARB). It is administered as a pro-drug that undergoes activation during gastrointestinal absorption. The agent is excreted mostly unchanged and has a terminal half-life of about nine hours (slightly longer in the elderly). Candesartan differs from other agents in its class in that it is tightly bound to angiotensin II type 1 receptors, allowing prolonged activity. In clinical trials, candesartan cilexetil has produced a dose-dependent effect when given in dosages of 2-32 mg/day. Observed trough-to-peak blood pressure ratios support a once-daily dosage regimen. The antihypertensive effect of candesartan cilexetil 4-16 mg/day was as great as that of enalapril 10-20 mg/day and amlodipine 5 mg/day and larger than that of losartan potassium 50 mg/day. Adding candesartan cilexetil to hydrochlorothiazide 12.5-25 mg/day and amlodipine 5 mg/day led to enhanced blood-pressure reductions and was well tolerated. It appears that candesartan can decrease renal perfusion without adversely affecting renal blood flow and may mediate a decrease in albuminuria in hypertensive patients with type 2 diabetes. No clinically important drug interactions have been reported. Adverse effects include headache, dizziness, nausea, diarrhea, and transient elevations in liver transaminases. The frequency of cough is similar to that seen with placebo. Candesartan cilexetil is an effective antihypertensive agent that can be used alone or in combination with other antihypertensive drugs. It is generally well tolerated and may be an option for patients who cannot tolerate angiotensin-converting-enzyme inhibitors because of cough.
Topics: Angiotensin II; Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Humans; Hypertension; Prodrugs; Randomized Controlled Trials as Topic; Tetrazoles
PubMed: 10786259
DOI: 10.1093/ajhp/57.8.739 -
Expert Opinion on Pharmacotherapy Jan 2008Although achieving blood pressure (BP) control is critical to improve cardiovascular prognosis in hypertensive patients, many of them fail to attain the targets. Most... (Review)
Review
Although achieving blood pressure (BP) control is critical to improve cardiovascular prognosis in hypertensive patients, many of them fail to attain the targets. Most patients with hypertension need more than one antihypertensive agent to achieve the goals. Combination therapy is required when monotherapy fails to attain BP objectives (< 140/90 mmHg in general hypertensive population; < 130/80 mmHg in high-risk groups) and as a first-line treatment in certain situations, such as markedly elevated BP values, high or very high cardiovascular risk patients or when lower targets are warranted. The advantages of combination therapy are well documented with the potential for increased antihypertensive efficacy as a result of different mechanisms of action, and a lower incidence of adverse effects because of the lower doses used and the possible compensatory responses. The inhibition of the renin-angiotensin system appears to be very beneficial in the treatment of patients with hypertension. Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg is the latest combination of an angiotensin receptor blocker and a diuretic approved for treatment of hypertension. The aim of this manuscript is to update the published data about the efficacy and safety of this fixed combination.
Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Drug Combinations; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Olmesartan Medoxomil; Tetrazoles; Treatment Outcome
PubMed: 18076344
DOI: 10.1517/14656566.9.1.129 -
Journal of Pharmaceutical Sciences Apr 1981Three trace impurities found in 4-acetyl-2-(2'-hydroxyethyl)-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one (II), a novel antihypertensive agent, were isolated by a...
Three trace impurities found in 4-acetyl-2-(2'-hydroxyethyl)-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one (II), a novel antihypertensive agent, were isolated by a combination of low-pressure liquid chromatography and preparative TLC. These impurities were identified as the formate ester of II, a pyridazinone having a 2-methyl rather than the 2'-hydroxyethyl substituent, and a bis(pyridazinonyl)methane analog. In addition, the product of O-alkylation rather than of N-alkylation of 4-acetyl-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one (I) with ethylene carbonate was detected by high-performance liquid chromatography. The biological activity of these four impurities was compared to that of II.
Topics: Animals; Antihypertensive Agents; Blood Pressure; Drug Contamination; Lethal Dose 50; Pyridazines; Rats
PubMed: 7229956
DOI: 10.1002/jps.2600700419 -
Drugs Nov 2000Lercanidipine is a vasoselective dihydropyridine calcium antagonist which causes systemic vasodilation by blocking the influx of calcium ions through L-type calcium... (Review)
Review
UNLABELLED
Lercanidipine is a vasoselective dihydropyridine calcium antagonist which causes systemic vasodilation by blocking the influx of calcium ions through L-type calcium channels in cell membranes. It is a highly lipophilic drug and as such has a slower onset and longer duration of action than a number of other calcium antagonists. Preclinical evidence suggests that lercanidipine has antiatherogenic potential and it may also protect against end-organ damage. In well controlled clinical studies, once daily administration of lercanidipine 10 or 20mg effectively reduced blood pressure (BP) compared with placebo in patients with mild to moderate hypertension without affecting heart rate. Response rate (percentage of patients with diastolic BP < or =90mm Hg or reduced by > or =10mm Hg from baseline) ranged from 50 to 66% with lercanidipine 10 mg/day and up to 86% with lercanidipine 20 mg/day. The drug had a long duration of action: clinical measurements for diastolic BP yielded a trough/peak ratio of >0.8 for both lercanidipine dosages in 1 study. Comparative trials, either published in full or as abstracts, found lercanidipine 10mg once daily for > or =4 weeks to be at least as effective as atenolol 50mg once daily, candesartan cilexetil 16 mg/day, captopril 25mg twice daily, enalapril 20 mg/day, hydrochlorothiazide 12.5mg once daily, irbesartan 150 mg/day and slow release nifedipine 20mg twice daily in patients with mild to moderate hypertension. In addition, lercanidipine 20 mg/day was as effective as amlodipine 10 mg/day. Lercanidipine is effective in the treatment of elderly patients (aged 60 to 85 years) with mild to moderate essential hypertension and in those with isolated systolic hypertension. In addition, monotherapy with lercanidipine 20 or 40 mg/day has shown efficacy in patients with severe hypertension, and add-on therapy helped control BP in a large proportion of patients with severe hypertension not responding sufficiently to beta-blockers, diuretics or ACE inhibitors. Unpublished data indicate that the drug reduces blood pressure in patients with type 2 (non-insulin-dependent) diabetes mellitus, without adversely affecting glucose homeostasis. Lercanidipine was well tolerated in clinical trials, with most treatment-related adverse events typical of dihydropyridine calcium antagonists, namely headache, flushing, dizziness and ankle oedema.
CONCLUSIONS
Lercanidipine is an effective and well tolerated once daily antihypertensive agent in patients with mild to moderate hypertension. In addition, the drug may reduce BP when used as monotherapy in patients with severe hypertension or when used adjunctively in patients with resistant hypertension. Importantly, lercanidipine appears to be at least as effective and well tolerated as other commonly used antihypertensive agents. The drug therefore represents a useful therapeutic option in the management of patients with hypertension and will be particularly useful in patients not responding to, or intolerant of, antihypertensive agents from other drug classes.
Topics: Administration, Oral; Antihypertensive Agents; Blood Pressure; Diabetes Complications; Dihydropyridines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Humans; Hypertension
PubMed: 11129125
DOI: 10.2165/00003495-200060050-00009 -
Blood Pressure. Supplement 1998Management strategies in hypertension evolve in response to an increased understanding of underlying pathophysiological processes and developments and refinements in... (Review)
Review
Management strategies in hypertension evolve in response to an increased understanding of underlying pathophysiological processes and developments and refinements in drug treatments. Recent research has identified the regulatory role of the imidazoline (I1) receptor in sympathetic outflow and blood pressure regulation and this has led to the development of moxonidine, a highly selective centrally acting antihypertensive agent. At a practical level, moxonidine is suitable for single daily dosing in hypertension. Furthermore, in comparative studies moxonidine has a low incidence of symptomatic adverse effects comparable, for example, to that of the ACE inhibitor drugs, captopril and enalapril. The antihypertensive efficacy of moxonidine has now been established in a series of comparative clinical trials against all other first-line antihypertensive drug classes but, in line with current concepts, it may be necessary to look beyond blood pressure reduction. For example, centrally acting agents are known to be effective for promoting the regression of LV hypertrophy and studies in hypertensive patients have shown that antihypertensive treatment with moxonidine successfully leads to significant reductions in LV mass indices. Furthermore, there is now evidence that moxonidine has a beneficial effect on insulin sensitivity such that there are likely to be improvements in the overall metabolic profile. Thus, the clinical characteristics of moxonidine indicate that it is well suited for consideration among the first-line antihypertensive treatment choices.
Topics: Antihypertensive Agents; Clinical Trials as Topic; Humans; Hypertension; Imidazoles
PubMed: 10321451
DOI: 10.1080/080370598438447-1 -
Pharmaceutical Patent Analyst Mar 2012Hypertension, defined as elevated systolic blood pressure and/or diastolic blood pressure generally greater than 140/90 mmHg, is a significant risk factor for... (Review)
Review
Hypertension, defined as elevated systolic blood pressure and/or diastolic blood pressure generally greater than 140/90 mmHg, is a significant risk factor for cardiovascular outcomes such as arterial aneurysm, myocardial infarction and stroke, and for nonvascular conditions such as Alzheimer's disease. The prevalence of the disease is rapidly increasing both in the USA and in the rest of the world. Hypertension can be managed to a degree through behavioral changes (e.g., reduction in salt intake and loss of excess body weight). When lifestyle changes fail, pharmacological therapy provides benefits, with combination drug therapy often required for many patients to reach their blood pressure-reduction goals. Approximately one-third of hypertensive patients who seek treatment fail to reach their goals, either because they are resistant to drug therapy or stop treatment due to side-effect issues. A medical need exists for new antihypertensive agents with improved risk-benefit profiles. However, within the past decade, the economics of bringing a new antihypertensive agent to market have become challenging due to the plethora of generic drugs available, the advent of polypharmacology, and the difficulty of identifying agents that are better than the standard of care. Only a few new mechanistic classes of antihypertensive agents have been recently approved, suggesting a lack of innovation within the industry. In this review, we describe the results of a survey of drug companies and drug classes in the 2007-2009 antihypertensive patent literature and comment on the current state of innovation in antihypertensive drug discovery.
Topics: Antihypertensive Agents; Drug Design; Drug Discovery; Drug Industry; Humans; Hypertension; Patents as Topic
PubMed: 24236713
DOI: 10.4155/ppa.12.5 -
Journal of Managed Care & Specialty... Jun 2019Approximately 32% (75 million) of adults have hypertension in the United States, leading to 1,100 daily deaths and costing more than $48 billion annually in medical... (Comparative Study)
Comparative Study
BACKGROUND
Approximately 32% (75 million) of adults have hypertension in the United States, leading to 1,100 daily deaths and costing more than $48 billion annually in medical expenditures. Approximately 25% of patients with hypertension require triple combination therapy to reach recommended blood pressure. Currently, only 3 single-pill triple-combination therapies are available in the market for the treatment of hypertension. Medication adherence has become a major concern for the health care system, and nonadherence is associated with higher risks of morbidity and mortality.
OBJECTIVE
To compare medication adherence rates among single-pill triple-combination therapy, free triple-combination therapy, and fixed-dose dual-combination therapy plus a third agent in hypertensive patients enrolled in a Medicare Advantage prescription drug plan using 2 adherence definitions.
METHODS
A retrospective cohort study was conducted using Cigna-HealthSpring's medical claims database from January 2014 to December 2016. Antihypertensive combination therapy users were classified into a single-pill triple-combination group, a fixed-dose dual-combination plus a third agent group, and a free triple-combination group. Adherence rates using proportion of days covered (PDC) were calculated for each group within a 1-year follow-up period using 2 definitions: a strict one requiring all antihypertensive agents during follow-up and a more relaxed definition requiring any antihypertensive agent during follow-up. Descriptive statistics were examined, and group differences were assessed using chi-square and analysis of variance. Multivariate logistic regression was conducted to control confounders of adherence using both definitions.
RESULTS
10,836 triple-combination users were identified. In the multivariate model using the first definition, fixed-dose dual-combination plus a third agent was significantly associated with lower adherence compared with single-pill triple therapy (OR = 0.177; 95% CI = 0.119-0.263; < 0.001). No significant difference was detected between single-pill triple-combination therapy in comparison with free-combination therapy. In the multivariate model using the second definition, fixed-dose dual-combination plus a third agent and free-combination therapy were significantly associated with better adherence in comparison with single-pill triple combination therapy (OR = 3.62, 95% CI = 2.59-5.05; OR = 4.31, 95% CI = 2.15-8.64, respectively). Younger age, female gender, language (Spanish), some comorbidities, and previous hospitalization had a negative effect on adherence.
CONCLUSIONS
Measuring adherence to multiple concurrent regimens is complicated and different adherence definitions can result in significant variations in adherence measures. Future research evaluating clinical outcomes with various definitions is needed.
DISCLOSURES
No outside funding supported this study. Abughosh reports grants from Sanofi, Regeneron, Valeant Pharmaceuticals, BMS/Pfizer, and PhRMA, not related to this study. Serna reports employement with CareAllies, a Cigna company. The other authors have no conflicts of interest to disclose.
Topics: Age Factors; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Medicare Part C; Medication Adherence; Middle Aged; Retrospective Studies; Sex Factors; United States
PubMed: 31134857
DOI: 10.18553/jmcp.2019.25.6.678 -
Nihon Naika Gakkai Zasshi. the Journal... Jan 2007
Review
Topics: Aged; Antihypertensive Agents; Humans; Hypertension
PubMed: 17305053
DOI: 10.2169/naika.96.35