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Vnitrni Lekarstvi 2021Blockade of the renin angiotensin aldosterone system (RAAS) is currently considered to be the gold standard of antihypertensive therapy. ACE inhibitors and AT1-blockers...
Blockade of the renin angiotensin aldosterone system (RAAS) is currently considered to be the gold standard of antihypertensive therapy. ACE inhibitors and AT1-blockers are clinically the most relevant groups of RAAS blockers. Even though both drug groups block angiotensin II, ACE inhibitors typically reduce the degradation of bradykinin, which leads to the release of nitric oxide and prostaglandins with subsequent vasodilation. These differences in the mechanism of action can be of clinical relevance for hypertensive patients. Morbidity mortality studies of RAAS blockers have been reported in which ACE inhibitors, particularly perindopril, improved the overall survival in hypertensive patients. In the ONTARGET trial, a direct comparison of both drug groups yielded comparable results. Perindopril, which has been used in the clinical practice for more than 25 years, is a long-acting lipophilic angiotensin-converting enzyme inhibitor with a once-daily dosage schedule and a high affinity to tissue-converting enzyme. Its safety, efficacy, and very good tolerance have been shown in a number of studies. It is part of many fixed combinations which improve patient compliance and increase the effect of treatment of cardiovascular diseases.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Humans; Hypertension; Perindopril; Renin-Angiotensin System
PubMed: 34074111
DOI: No ID Found -
Chemico-biological Interactions Jan 2022The use of methotrexate (MTX), a classical immunosuppressant and anti-cancer agent, is associated with multiple organ toxicities, including the intestinal injury....
Targeting inflammation and redox aberrations by perindopril attenuates methotrexate-induced intestinal injury in rats: Role of TLR4/NF-κB and c-Fos/c-Jun pro-inflammatory pathways and PPAR-γ/SIRT1 cytoprotective signals.
AIMS
The use of methotrexate (MTX), a classical immunosuppressant and anti-cancer agent, is associated with multiple organ toxicities, including the intestinal injury. Components of the renin-angiotensin system are expressed in the intestinal epithelium and mucosal immune cells where they provoke pro-inflammatory and pro-oxidant action. The present study was conducted to investigate the potential ability of perindopril (PER), an angiotensin-converting enzyme inhibitor (ACEI), to attenuate MTX-induced intestinal injury with emphasis on the role of the pro-inflammatory TLR4/NF-κB and c-Fos/c-Jun pathways alongside PPAR-γ and SIRT1 cytoprotective signals.
MATERIALS AND METHODS
The intestinal injury was induced by a single-dose injection of 20 mg/kg of MTX i.p at the end of the 5th day. PER was administrated once daily in a dose of 1 mg/kg, i.p, for five days before MTX and five days later.
RESULTS
Herein, perindopril attenuated the intestinal injury as seen by lowering the histopathological aberrations and preserving the goblet cells in villi/crypts. These beneficial actions were associated with downregulating the expression of the pro-inflammatory angiotensin II, TNF-α, IL-1β, and IL-6 cytokines, alongside upregulating the anti-inflammatory angiotensin (1-7) and IL-10. At the molecular level, perindopril downregulated the TLR4/NF-κB and c-Fos/c-Jun pathways in inflamed intestine of rats. Moreover, it attenuated the pro-oxidant events by lowering intestinal MDA and boosting GSH, SOD, and GST antioxidants together with PPAR-γ and SIRT1 cytoprotective signals. The aforementioned findings were also highlighted using molecular docking and network pharmacology analysis.
CONCLUSIONS
Perindopril demonstrated notable mitigation of MTX-induced intestinal injury through suppression of TLR4/NF-κB and c-Fos/c-Jun pathways alongside the augmentation of PPAR-γ/SIRT1 cytoprotective signals.
Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Intestinal Diseases; Intestines; JNK Mitogen-Activated Protein Kinases; Male; Methotrexate; Molecular Docking Simulation; NF-kappa B; Oxidative Stress; PPAR gamma; Perindopril; Protein Binding; Proto-Oncogene Proteins c-fos; Rats, Wistar; Signal Transduction; Sirtuin 1; Toll-Like Receptor 4; Rats
PubMed: 34737150
DOI: 10.1016/j.cbi.2021.109732 -
European Journal of Pharmacology Nov 2015The aim of this study was to evaluate the effects of perindopril or barnidipine alone or combined with simvastatin on metabolic parameters and hepatic steatosis degree.... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
The aim of this study was to evaluate the effects of perindopril or barnidipine alone or combined with simvastatin on metabolic parameters and hepatic steatosis degree. One hundred and forty nine mild to moderate hypertensive, normocholesterolemic, overweight or obese outpatients with hepatic steatosis were enrolled. They were treated with perindopril 5mg/day, or barnidipine, 20mg/day, for 6 months; subsequently simvastatin, 20mg/day was added to both treatments for further 6 months. Blood pressure variation was recorded. Patients also underwent an ultrasound examination, at baseline and after 6, and 12 months. We also assessed: fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), tumor necrosis factor-α (ΤΝF-α), interleukin-6 (IL-6), high-sensitivity C reactive protein (Hs-CRP). Both perindopril and barnidipine reduced blood pressure, with barnidipine being more effective. Barnidipine, but not perindopril, slightly decreased total cholesterol and triglycerides after 6 months compared to baseline; lipid profile improved in both groups when simvastatin was added. Regarding inflammatory parameters, barnidipine reduced TNF-a, IL-6, and Hs-CRP, both in monotherapy, and after simvastatin addition. Hepatic steatosis parameters improved only when simvastatin was added. We can conclude that barnidipine better reduced blood pressure compared to perindopril and inflammatory parameters. Regarding hepatic steatosis parameters, only the addition of simvastatin improved them.
REGISTRATION NUMBER
NCT02064218, ClinicalTrials.gov.
Topics: Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Hypolipidemic Agents; Male; Nifedipine; Non-alcoholic Fatty Liver Disease; Obesity; Perindopril; Simvastatin
PubMed: 26407654
DOI: 10.1016/j.ejphar.2015.09.030 -
Analytical and Bioanalytical Chemistry Oct 2017A first of its kind, simple, rapid, and sensitive liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated for quantification of perindopril...
A first of its kind, simple, rapid, and sensitive liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated for quantification of perindopril and perindoprilat in both human plasma and breast milk. The analytes and internal standards (phenazone and acetyl salicylic acid) were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column was used to provide an appropriate chromatographic separation of the analytes, followed by detection with tandem mass spectrometry. Gradient chromatographic and mass spectrometric detection conditions with mobile phases (A: 5% methanol + 0.1% formic acid in water v/v, and B: 95% methanol + 0.1% formic acid in water v/v) were developed to achieve a LOQ of 0.5 ng/mL in both human plasma and milk. The method was suitable of evaluating clinical samples. The mass transition was followed as m/z 369.10/172.00 for perindopril, m/z 339.00/168.10 for perindoprilat, m/z 188.90/55.95 for phenazone, and m/z 179.04/137.02 for acetyl salicylic acid. The developed method was optimized and validated with a linear range of 0.1-200 ng/mL (r = better than 0.99 for both perindopril and perindoprilat). The precision and accuracy values were within 15% CV. The overall recovery of the analytes was 80-110%. The method has good specificity and repeatability. Stability studies were conducted in both human plasma and bovine milk for up to 3 months, at the storage conditions of 25, 4, and -80 °C.
Topics: Angiotensin-Converting Enzyme Inhibitors; Breast Feeding; Chromatography, Liquid; Female; Humans; Indoles; Limit of Detection; Milk, Human; Perindopril; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 28842738
DOI: 10.1007/s00216-017-0552-y -
Journal of Applied Biomedicine Dec 2020Rosuvastatin Calcium and Ezetimibe are used to control cholesterol level while Perindopril Erbumine is used to treat hypertension. Hepatic metabolism reduces the...
BACKGROUND
Rosuvastatin Calcium and Ezetimibe are used to control cholesterol level while Perindopril Erbumine is used to treat hypertension. Hepatic metabolism reduces the therapeutic effect of these drugs.
OBJECTIVE
Instant release buccal films (IRBFs) could possibly be a solution to this issue. The objective of the study was to formulate IRBFs of Rosuvastatin Calcium, Perindopril Erbumine and Ezetimibe using solvent casting technique.
METHODS
Polymers used to prepare IRBFs included hydroxypropyl methylcellulose (HPMC E5), PEG 400 (as plasticizer) and Tween 80 (as surfactant). Solvent casting technique was used to fabricate the films, followed by their in-vitro analysis including high performance liquid chromatography (HPLC), X-ray diffraction (XRD), fourier transform infrared evaluation (FTIR), In-vitro dissolution, In-vitro disintegration, stability tests, scanning electron microscopy (SEM), folding fortitude, thickness evaluation, surface pH, tensile strength, weight variation and percentage moisture content.
RESULTS
Optical microscopy as well as SEM analysis displayed that the surfaces of IRBFs were smooth with uniform mixing of ingredients. IRBFs disintegrated within 15 seconds while on dissolution they exhibited instant drug release i.e. 100% release in 2 minutes.
CONCLUSIONS
The results show promising potential of IRBFs in drug delivery.
Topics: Ezetimibe; Hypromellose Derivatives; Perindopril; Rosuvastatin Calcium; Solvents
PubMed: 34907764
DOI: 10.32725/jab.2020.015 -
Clinical Therapeutics Oct 2021The efficacy and tolerability of fimasartan in elderly patients have not been fully evaluated. This study was therefore conducted to determine the efficacy and... (Randomized Controlled Trial)
Randomized Controlled Trial
A Randomized, Double-blind, Active-controlled, Two Parallel-Group, Optional Titration, Multicenter, Phase IIIb Study to Evaluate the Efficacy and Safety of Fimasartan Versus Perindopril Monotherapy With and Without a Diuretic Combination in Elderly Patients With Essential Hypertension.
PURPOSE
The efficacy and tolerability of fimasartan in elderly patients have not been fully evaluated. This study was therefore conducted to determine the efficacy and tolerability of fimasartan compared with perindopril in elderly Korean patients aged >70 years with essential hypertension (defined by a mean sitting systolic blood pressure [SBP] ≥140 mm Hg).
METHODS
This randomized, double-blind, active-controlled, 2 parallel-group, optional titration, multicenter, Phase IIIb trial (FITNESS [Fimasartan in the Senior Subjects]) enrolled 241 patients from 23 cardiac centers in the Republic of Korea between August 2017 and December 2019. After the placebo run-in period, treatment started with fimasartan 30 mg or perindopril arginine 2.5 mg once daily at a 1:1 ratio; if BP was not controlled at week 4, the dose was doubled. If BP was not controlled at week 8, a diuretic combination (fimasartan 60 mg/hydrochlorothiazide 12.5 mg or perindopril arginine 5 mg/indapamide 1.25 mg) was administered. After 16 weeks of the double-blind treatment, the patients with controlled BP participated in an 8-week open-label extension study, with the 2 groups unified by fimasartan 60 mg with or without hydrochlorothiazide 12.5 mg for 8 weeks. The primary outcome was a change in SBP for 8 weeks. The secondary outcomes included a change in sitting diastolic BP (DBP) for 8 weeks and changes in SBP and DBP for 4, 16, and 24 weeks.
FINDINGS
At week 8, mean SBP significantly decreased from baseline in both groups: -14.2 (14.4) mm Hg in the fimasartan group and -9.0 (16.1) mm Hg in the perindopril group. The difference between the 2 groups was 5.4 (2.1) mm Hg, indicating the noninferiority of fimasartan to perindopril. Moreover, fimasartan exhibited a higher BP-lowering effect than perindopril (P = 0.0108). In addition, reductions in SBP and DBP from baseline to weeks 4, 8, and 16 were significantly greater in the fimasartan group than in the perindopril group, although the SBP reduction was comparable at week 16. Both groups reported an excellent mean compliance rate of 97.4% (4.7%) through week 16. During the study period, 82 adverse events were reported in 52 patients, 40 in the fimasartan group and 42 in the perindopril group (P = 0.4647). Dizziness was the most commonly reported adverse event (7 cases). Remarkably, only 1 case of orthostatic hypotension was reported during the study period.
IMPLICATIONS
In elderly patients with essential hypertension, fimasartan 30 to 60 mg with a possible hydrochlorothiazide 12.5-mg combination was noninferior to perindopril 2.5 to 5 mg with a possible indapamide 1.25-mg combination. Furthermore, fimasartan exhibited higher BP-lowering efficacy than perindopril. There was no difference in tolerability between the 2 groups. Clinicaltrials.gov Identifier: NCT03246555.
Topics: Aged; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Diuretics; Double-Blind Method; Drug Therapy, Combination; Essential Hypertension; Humans; Perindopril; Pyrimidines; Tetrazoles; Treatment Outcome
PubMed: 34503866
DOI: 10.1016/j.clinthera.2021.08.003 -
Kardiologiia Apr 2017High prevalence of arterial hypertension and low rate of blood pressure (BP) control in patients with arterial hypertension require more intensive approaches to... (Review)
Review
High prevalence of arterial hypertension and low rate of blood pressure (BP) control in patients with arterial hypertension require more intensive approaches to antihypertensive therapy. Every patient with arterial hypertension is characterized by different predominant pathophysiologic mechanisms in different periods of his life. Because of impact on different pathophysiologic mechanisms combined antihypertensive therapy allows to achieve more pronounced BP reduction, decrease heterogeneity of response and alleviate side effects of each component. Use of fixed drug combinations improves adherence to treatment and thus its efficacy. Novel fixed-dose combination of amlodipine, indapamide and perindopril fully realizes principles underlying modern antihypertensive therapy. Antihypertensive effectiveness of components of this combination has been confirmed by the results of international trials.
Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Combinations; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Hypertension; Indapamide; Perindopril
PubMed: 28762910
DOI: No ID Found -
European Journal of Internal Medicine Apr 2023Angiotensin converting enzyme inhibitors (ACEi) have consistently demonstrated improved survival and reduced risk of major cardiovascular events, across the spectrum of... (Review)
Review
Angiotensin converting enzyme inhibitors (ACEi) have consistently demonstrated improved survival and reduced risk of major cardiovascular events, across the spectrum of cardiovascular disease, including hypertension, coronary artery disease, myocardial infarction, and heart failure. The cardioprotective effects of ACEi result from inhibiting the conversion of angiotensin I to angiotensin II, and inhibition of bradykinin degradation. They are generally well tolerated but may cause the onset of a dry cough in some patients. This review presents current evidence on the incidence and mechanisms of cough associated with ACEi use, and then considers how to manage ACEi-related cough in clinical practice. The incidence of ACEi-induced cough in the published literature varies widely due to heterogeneity in the source data and lack of adequate controls. Incidence also varies among individual ACEi with agents such as perindopril, which has a high tissue ACE affinity, associated with a lower rate of cough. Evidence from real-world studies shows that the incidence of ACEi-associated cough is lower than rates reported in clinical trials. Patients who experience any dry cough are often switched to angiotensin- receptor blockers or other classes of antihypertensive drugs, regardless of cough severity. To avoid inappropriate discontinuation of ACEi in clinical practice, an alternative approach in patients with persistent cough is to perform a challenge/re-challenge to determine if re-introduction of ACEi is associated with recurrence of symptoms. Incidence of cough should not be considered a class effect for ACEi, and the patient may benefit by a switch from one ACEi to another. Every effort should be made to enable patients to continue ACEi therapy to reduce adverse cardiovascular outcomes and improve survival.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Cough; Antihypertensive Agents; Hypertension; Angiotensin Receptor Antagonists; Myocardial Infarction
PubMed: 36628825
DOI: 10.1016/j.ejim.2023.01.005 -
Annals of Medicine and Surgery (2012) Nov 2021and importance: Shone complex is a congenital heart defect consisting of four obstructive defects in the left heart: a mitral supravalvular ring, sub-aortic stenosis,...
INTRODUCTION
and importance: Shone complex is a congenital heart defect consisting of four obstructive defects in the left heart: a mitral supravalvular ring, sub-aortic stenosis, parachute mitral valve, and coarctation of the aorta (CoA), which affects only a small minority of people.
CASE PRESENTATION
We report the case of a 25-year-old woman with a past medical history of moderate mitral stenosis, since she was 10-year-old with uncontrolled high blood pressure, treated with nicardipine. admitted to our emergency department with high blood pressure: 190/80 mmhg, in whom The transthoracic echocardiography (TTE) revealed: sub-mitral membrane, with a single sub-papillary muscle, and coarctation of the aorta and the CT scan showed narrowed aortic arch and a left superior vena cava allowing to retain shone syndrome as the main diagnosis. The patient was treated with an antihypertensive treatment combining (perindopril/indapamide/amlodipine) while waiting for surgery.
CLINICAL DISCUSSION
In this mini-review, we aim to describe this rare pathological condition its pathophysiological thoughts, and the way to diagnosis this complex early.
CONCLUSION
Treatment required the coordinated efforts of a team of specialists. It could be either surgical with different method or by Trans catheter treatments.
PubMed: 34729182
DOI: 10.1016/j.amsu.2021.102955 -
Revue Medicale de Liege Apr 2018The endothelium plays a vital role as part of the cardiovascular continuum. Risk factors such as hypertension and dyslipidemia unbalance angiotensin II - bradykinin... (Review)
Review
The endothelium plays a vital role as part of the cardiovascular continuum. Risk factors such as hypertension and dyslipidemia unbalance angiotensin II - bradykinin homeostasis, leading to endothelial dysfunction and changes in vascular structure that promote atherosclerosis and thrombosis. When dealing with risk factors, treatment should focus on the prevention and restoration of endothelial function. Not all cardiovascular drugs are able to reverse vascular and structural endothelial dysfunction. Increasing levels of bradykinin is an effect of the use of angiotensin-converting enzyme inhibitors (ACE-Is), and also a fundamental part of their mode of action. The cardiovascular protection observed with ACE-I, and not with sartans, can be explained rationally by the specific effects of bradykinin on the endothelium. In the pharmacological class of ACE-Is, perindopril likely produces the strongest effects on bradykinin, which may explain, at least in part, the documented superiority of this drug in the prevention and treatment of cardiovascular disease.
Topics: Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Cardiovascular Diseases; Endothelium, Vascular; Humans; Perindopril
PubMed: 29676873
DOI: No ID Found