Captopril

The fixed combination of zofenopril 30 mg plus hydrochlorothiazide 12.5 mg is indicated for the management of hypertensive patients whose blood pressure (BP) is not adequately controlled on zofenopril alone. In clinical trials, this combination therapy proved to be superior to monotherapy in reducing office and ambulatory BP. In this review, the authors have updated the current evidence on the efficacy of the zofenopril plus hydrochlorothiazide combination in light of the results of the recent ZODIAC study on previously monotherapy-treated uncontrolled hypertensive patients with associated cardiovascular risk factors. The trial documented a similar BP control under this combination and with irbesartan plus hydrochlorothiazide, but a larger reduction of high-sensitivity C-reactive protein, suggesting a potential protective effect against vascular inflammation. Thus, the fixed combination of zofenopril plus hydrochlorothiazide may have a particular place in the treatment of high-risk ...

Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hyp...

A double-blind, randomized, parallel and active-controlled clinical study was conducted to evaluate the anti-hypertensive effect as well as the tolerability of Olive leaf extract in comparison with Captopril in patients with stage-1 hypertension. Additionally, this study also investigated the hypolipidemic effects of Olive leaf extract in such patients. It consisted of a run-in period of 4 weeks continued subsequently by an 8-week treatment period. Olive (Olea europaea L.) leaf extract (EFLA®943) was given orally at the dose of 500 mg twice daily in a flat-dose manner throughout the 8 weeks. Captopril was given at the dosage regimen of 12.5 mg twice daily at start. After 2 weeks, if necessary, the dose of Captopril would be titrated to 25 mg twice daily, based on subject's response to treatment. The primary efficacy endpoint was reduction in systolic blood pressure (SBP) from baseline to week-8 of treatment. The secondary efficacy endpoints were SBP as well as diastolic blood pressure (DBP) changes at every time-point evaluation and lipid profile improvement. Evaluation of BP was performed every week for 8 weeks of treatment; while of lipid profile at a 4-week interval. Mean SBP at baseline was 149.3 ± 5.58 mm Hg in Olive group and 148.4 ± 5.56 mm Hg in Captopril group; and mean DBPs were 93.9 ± 4.51 and 93.8 ± 4.88 mm Hg, respectively. After 8 weeks of treatment, both groups experienced a significant reduction of SBP as well as DBP from baseline; while such reductions were not significantly different between groups. Means of SBP reduction from baseline to the end of study were −11.5 ± 8.5 and −13.7 ± 7.6 mm Hg in Olive and Captopril groups, respectively; and those of DBP were −4.8 ± 5.5 and −6.4 ± 5.2 mm Hg, respectively. A significant reduction of triglyceride level was observed in Olive group, but not in Captopril group. In conclusion, Olive (Olea europaea) leaf extract, at the dosage regimen of 500 mg twice daily, was similarly effective in lowering systolic and diastolic blood pressures in subjects with stage-1 hypertension as Captopril, given at its effective dose of 12.5–25 mg twice daily.

CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective. Although esthetically unpleasing to use so many drugs at once, the closely similar drugs of the original CUSP9 used together have been well-tolerated when given on a compassionate-use basis in the cases that have come to our attention so far. We expect similarly good tolerability for CUSP9*. The combined action of this suite of drugs blocks signaling at, or the activity of, AKT phosphorylation, aldehyde d...

The objective of this study was to assess the antihypertensive effect and the trough to peak (T:P) ratio of lisinopril and captopril, in patients with essential hypertension. After 2 weeks of placebo, 69 of 115 eligible patients had office diastolic blood pressure (DBP) between 90 and 114 mm Hg and daytime average DBP above 85 mm Hg during a 25-h

The humoral and hemodynamic effects of converting enzyme inhibition captopril are presented in two patients with primary hyperaldosteronism (PHA). In all, 20 patients with resistant hypertension were treated with the angiotensin converting enzyme inhibitor captopril. In 18 patients with essential or renovascular hypertension mean (+/- SEM) plasma renin activity (PRA) rose from 5.0 +/- 1.4 to 35.3 +/- 5.3 ng/ml/hr (P less than 0.01) and mean (+/- SEM) plasma aldosterone (PA) declined from 25.8 +/- 2.9 to 15.1 +/- 1.9 ng/ml (P less than 0.01) after captopril. In two patients with PHA the PRA was not stimulated by converting enzyme inhibition, although there was modest decline in PA and a temporary reduction in blood pressure. After surgical removal of aldosterone-producing adenomas, PRA responsed appropriately to captopril. These cases illustrate that a disease process can modify the response to a drug and demonstrate that, in patients with PHA, captopril does not stimulate PRA, induc...

Lung cancer is the most common form of cancer in the world, and 90% of patients die from their disease. The angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents, and it has been suggested that they decrease the risk of some cancers, although available data are conflicting. Accordingly, we investigated the anticancer activity of the ACE inhibitor, captopril, in athymic mice injected with highly tumorigenic LNM35 human lung cells as xenografts. Using this model, we demonstrated that daily IP administration of captopril (2.8 mg/mouse) for 3 weeks resulted in a remarkable reduction of tumor growth (58%, P < 0.01) and lymph node metastasis (50%, P= 0.088). There were no undesirable effects of captopril treatment on animal behavior and body weight. In order to determine the mechanism by which captopril inhibited tumor growth, we investigated the impact of this drug on cell proliferation, apoptosis, and angiogenesis. Immunohistochemical analysis demonstrated that captopril treatment significantly reduced the number of proliferating cells (Ki-67) in the tumor samples but was not associated with inhibition of tumor angiogenesis (CD31). Using cell viability and fluorescent activated cell sorting analysis tests, we demonstrated that captopril inhibited the viability of LNM35 cells by inducing apoptosis, providing insight about the mechanisms underlying its antitumorigenic activities. In view of these experimental findings, we conclude that captopril could be a promising option for the treatment of lung cancer.

The renin-angiotensin system is associated with a variety of pathophysiological processes in many organ systems, and is known to be involved in the normal regulation of blood pressure and in the pathogenesis of renovascular hypertension. Angiotensin II is a multifunctional hormone that manifests its properties by interacting with two major subtypes of cell surface receptors (AT1 and AT2). Angiotensin converting enzyme (ACE) inhibitors are able to modify the actions of the renin-angiotensin system, and are indicated for the treatment of hypertension and heart disease. The antihypertensive effects of ACE inhibiting drugs are related to their ability to block the conversion of the decapeptide, angiotensin I, to the potent pressor octapeptide, angiotensin II. ACE inhibitors have been implicated in fetopathies in humans and perinatal mortality in rats, rabbits, sheep and baboons. Human fetopathies were seen when ACE inhibitors were given around the 26th week of gestation. The major adver...

Development and validation of analytical methods of captopril tablets have been carried out by absorbance method and area under the curve method by UV-Vis spectrophotometry. This study used absorbance calculation principle and area under the curve obtained from measurement of analytical solution using UV-Vis spectrophotometer and distilled water as solvent with several reagents. This reagent is used to oxidize captopril compounds having thiol (-SH) groups in their structure. Captopril linearity was obtained in the concentration range 20 - 60 μg/mL. Correlation coefficient value with absorbance method and area under the curve method are 0.9998 and 0.9994 respectively. The results showed that the sample rate obtained by absorbance method and area under the curve method were 104.55 % ± 0.433 and 92.22 % ± 0.351 for patent tablets; 93.42 % ± 1.306 and 91.09 % ± 0.093 for generic tablets. The average per cent of recovery obtained by absorbance method and area under the curve method were 95.62 % ± 14.444 and 101.55% ± 15.989 for patent tablets; 95.33 % ± 14.278 and 100.96 % ± 15.655 for generic tablets.

The role of angiotensin II (ANG II) in the development of isoproterenol (Iso)-induced cardiac hypertrophy was examined in rats. Iso increased cardiac mass, left ventricular RNA-to-DNA ratio, and the cardiac content of both myosin heavy chain and hydroxyproline in a dose-dependent manner, indicating that Iso-induced cardiac hypertrophy involves growth of both muscle and connective tissue. Cardiac hypertrophy reverted within 11-14 days after cessation of Iso. Propranolol prevented development of Iso-induced cardiac hypertrophy but did not affect the rate of its reversal. The ANG II receptor blocker losartan (Los) did not significantly decrease the hypertrophic response to Iso. Los injected after cessation of Iso dramatically enhanced the reversal of cardiac hypertrophy, even in rats that received Los with Iso during the induction of Iso-induced cardiac hypertrophy. ANG II, injected continuously at a subpressor dose that did not affect heart weight when given alone, inhibited reversal of cardiac hypertrophy when given after cessation of Iso. Los did not significantly affect the induction of the protooncogene c-fos by Iso. We conclude that endogenous ANG II has a major function in maintaining Iso-induced cardiac hypertrophy but does not mediate its induction. This suggests that different interactive stimuli may be required for development of cardiac hypertrophy, i.e., for initiation and for maintenance.

O sistema renina-angiotensina II- aldosterona é uma cascata hormonal envolvida no controle da pressão arterial, volemia e equilíbrio hidroeletrolítico. A desregulação do SRAA (Sistema Renina-Angiotensina- Aldosterona) desempenha um papel importante na patogênese de doenças renais, cardiovasculares e na hipertensão arterial (GIESTA, 2010). Consequentemente esse sistema SRAA é um alvo de grande importância terapêutica para diversos fármacos entre eles os inibidores de angiotensina. O artigo abordará a fisiologia e o mecanismo de ação dos fármacos inibidores de angiotensina.

We tested the ability of captopril treatment (50 mg/kg/day p.o.), initiated 2 weeks before stroke or up to 5 days after stroke, to alter the onset of stroke and death after stroke in Kyoto Wistar stroke-prone spontaneously hypertensive rats (SHRsp). The benefits of blood pressure and aldosterone suppression during captopril treatment were assessed. SHRsp developed a 100% mortality rate with intracerebral hemorrhage by 16 weeks of age. Captopril treatment, started 2 weeks before or at the initiation of stroke, suppressed plasma aldosterone and equally prevented mortality to a mean age of &gt;27 weeks. Treatment started 5 days after stroke extended the mean lifespan to &gt;23 weeks. The re-elevation of plasma aldosterone (via osmotic pumps to levels in untreated SHRsp) during captopril treatment, before stroke, allowed stroke to develop. The initiation of the latter manipulation in pre- or poststroke captopril-treated SHRsp at a latter age (23 weeks) didn&#39;t alter the lifespan of S...