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Journal of Advanced Pharmaceutical... Jul 2014The aim was to evaluate the analgesic activity of perindopril in chemical, thermal and mechanical pain on Swiss albino mice. A total of 54 albino mice (Swiss strain)...
The aim was to evaluate the analgesic activity of perindopril in chemical, thermal and mechanical pain on Swiss albino mice. A total of 54 albino mice (Swiss strain) weighing 25-30 g were allocated to each experimental model and in each model there were three groups. The control group received normal saline (25 ml/kg) per orally, standard group received pentazocine (10 mg/kg) intra-peritoneal and test groups received perindopril (1 mg/kg) per orally. Perindopril and normal saline was administered 2 h before, whereas the pentazocine was administered 15 min prior to Eddy's hot plate, writhing and tail clip methods. The decrease in number of writhes, the delay in reaction time in tail clip and Eddy's hot plate method denoted the analgesic activity. Perindopril decreased the number of writhes, delayed the reaction time in tail clip and Eddy's hot plate method considerably when compared with control (normal saline), but less when compared with standard (pentazocine). Perindopril exhibits analgesic activity in thermal, chemical, and mechanical pain models in albino mice.
PubMed: 25126534
DOI: 10.4103/2231-4040.137423 -
Clinical and Translational Science Nov 2021Previous studies showed that postmenopausal women are more likely to have poorly controlled hypertension than men of the same age. Whether this is caused by inadequate...
Previous studies showed that postmenopausal women are more likely to have poorly controlled hypertension than men of the same age. Whether this is caused by inadequate treatment or poor response to antihypertensive agents remains unknown. The aim of this study is to analyze treatment response to the most potent renin angiotensin aldosterone system (RAAS) inhibitor perindopril in different age categories in women and men. Individual patient data were used from the combined European Trial on Reduction of Cardiac Events With Perindopril (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS), and Action in Diabetes and Vascular disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trials, which include patients with vascular disease (n = 29,463). We studied the relative and absolute changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) during a 4-week run-in phase in which all patients were treated with the perindopril-based treatment in different age categories. In total, 8366 women and 21,097 men were included in the analysis. Women greater than 65 years of age showed a significantly smaller blood pressure reduction after perindopril treatment (2.8 mmHg [95% confidence interval {CI} = 0.1-5.5] less reduction compared to women ≤45 years, p = 0.039). In men, the SBP reduction after perindopril in patients greater than 55-65 and greater than 65 years was lower compared to the age category less than or equal to 45 years (adjusted mean difference >55-65: 2.8 mmHg [95% CI = 1.8-3.7], p < 0.001, >65: 3.7 mmHg [95% CI = 2.7-4.7], p < 0.001). A trend of less blood pressure reduction was seen with ageing in both men and women (p < 0.001). To conclude, we observed that in both women and men the perindopril leads to less SBP reduction with increasing age, whereas the DBP reduction increases with age. More research is needed to determine whether it would be beneficial to use age-adjusted perindopril dosages.
Topics: Adult; Age Factors; Aged; Antihypertensive Agents; Blood Pressure; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Perindopril
PubMed: 34080302
DOI: 10.1111/cts.13076 -
Biomedicine & Pharmacotherapy =... Apr 2023The hormone, relaxin (RLX), exerts various organ-protective effects independently of etiology. However, its complex two-chain and three disulphide bonded structure is a...
The single-chain relaxin mimetic, B7-33, maintains the cardioprotective effects of relaxin and more rapidly reduces left ventricular fibrosis compared to perindopril in an experimental model of cardiomyopathy.
The hormone, relaxin (RLX), exerts various organ-protective effects independently of etiology. However, its complex two-chain and three disulphide bonded structure is a limitation to its preparation and affordability. Hence, a single chain-derivative of RLX, B7-33, was developed and shown to retain the anti-fibrotic effects of RLX in vitro and in vivo. Here, we determined whether B7-33 could retain the other cardioprotective effects of RLX, and also compared its therapeutic efficacy to the ACE inhibitor, perindopril. Adult male 129sv mice were subjected to isoprenaline (ISO; 25 mg/kg/day, s.c)-induced cardiomyopathy, then s.c-treated with either RLX (0.5 mg/kg/day), B7-33 (0.25 mg/kg/day; equivalent dose corrected for MW) or perindopril (1 mg/kg/day) from days 7-14 post-injury. Control mice received saline instead of ISO. Changes in animal body weight (BW) and systolic blood pressure (SBP) were measured weekly, whilst cardiomyocyte hypertrophy and measures of vascular dysfunction and rarefaction, left ventricular (LV) inflammation and fibrosis were assessed at day 14 post-injury. ISO-injured mice had significantly increased LV inflammation, cardiomyocyte hypertrophy, fibrosis, vascular rarefaction and aortic contractility in the absence of any changes in BW or SBP at day 14 post-injury. Both B7-33 and RLX equivalently reduced LV fibrosis and normalised the ISO-induced LV inflammation and cardiomyocyte hypertrophy, whilst restoring blood vessel density and aortic contractility. Comparatively, perindopril lowered SBP and the ISO-induced LV inflammation and vascular rarefaction, but not fibrosis or hypertrophy. As B7-33 retained the cardioprotective effects of RLX and provided rapid-occurring anti-fibrotic effects compared to perindopril, it could be considered as a cost-effective cardioprotective therapy.
Topics: Mice; Animals; Male; Perindopril; Relaxin; Microvascular Rarefaction; Cardiomyopathies; Models, Theoretical; Inflammation; Hypertrophy
PubMed: 36753958
DOI: 10.1016/j.biopha.2023.114370 -
Pharmacological Reports : PR 2010This study describes a modification of Vane's blood-bathed organ technique (BBOT). This new technique consisted of replacing the cascade of contractile smooth muscle... (Review)
Review
This study describes a modification of Vane's blood-bathed organ technique (BBOT). This new technique consisted of replacing the cascade of contractile smooth muscle organs within the traditional BBOT by a single collagen strip cut from a rabbit's hind leg tendon. Utilizing the extracorporeal circulation of an anesthetized heparinized mongrel cat or Wistar rat, arterial blood was dripped (1-3 ml min(-1)) over a collagen strip. This resulted in a gain in weight of the strip, which was due to the deposition of platelet aggregates and a few blood cells trapped over the strip. Arterial blood that had been used for the superfusion was pumped back into the animal's venous system. However, when this technique is adapted to human volunteers, the superfusing blood should be discarded. In animal experiments, intravenous injections of a variety of classic fibrinolytic agents (e.g., streptokinase) promoted the formation of platelet thrombi. Nitric oxide donors (e.g., SIN-1) at non-hypotensive doses hardly affected the mass of platelet thrombi deposited over the collagen strip, whereas endogenous prostacyclin (e.g., released from vascular endothelium by bradykinin) or exogenous prostacyclin and its stable analogues (e.g., iloprost) dissipated platelet thrombi as measured by a loss in the weight of the blood superfused collagen strip. This model allowed us to assay numerous drugs for their releasing properties of endogenous prostacyclin from vascular endothelium. These drugs included lipophilic angiotensin converting enzyme inhibitors (ACE-Is), which act in vivo as bradykinin potentiating factors (BPF). Other PGI(2)-releasers included statins (e.g., atorvastatin and simvastatin), thienopyridines (e.g., ticlopidine and clopidogrel), a number of thromboxane synthase inhibitors, flavonoids, bradykinin itself, cholinergic M receptor agonists and nicotinic acid derivatives. The thrombolytic actions of lipophilic ACE-Is (e.g., quinapril and perindopril) were prevented by pretreatment with either bradykinin B(2) receptor antagonists (e.g., icatibant) or with endothelial COX-2 inhibitors (e.g., rofecoxib, celecoxib and high dose aspirin). The inhibition of endothelial nitric oxide synthetase (eNOS) by L-NAME hardly blunted the thrombolytic response to ACE-Is. Hence, it can be concluded that many recognized cardiovascular drugs apart from their known basic mechanisms of action, may also behave as releasers of endogenous endothelial prostacyclin. Furthermore, in many instances, this effect may be the primary mechanism of their therapeutic efficacy.
Topics: Animals; Biological Assay; Cardiovascular Agents; Cats; Collagen; Endothelium, Vascular; Epoprostenol; Humans; Rabbits; Rats; Rats, Wistar; Tendons
PubMed: 20631409
DOI: 10.1016/s1734-1140(10)70301-7 -
Advances in Therapy Jun 2022Most patients with hypertension in sub-Saharan Africa require two or more drugs to control their blood pressure. Triple fixed-dose combination therapy of perindopril... (Observational Study)
Observational Study
INTRODUCTION
Most patients with hypertension in sub-Saharan Africa require two or more drugs to control their blood pressure. Triple fixed-dose combination therapy of perindopril arginine/indapamide/amlodipine is more effective in lowering blood pressure, offers better target organ protection and has increased adherence compared to monotherapy and free combination therapy, and is safe to use. This observational study evaluates the effectiveness of perindopril arginine/indapamide/amlodipine in controlling blood pressure at least 1 month after treatment initiation and assesses patient- and physician- reported drug tolerance over a 3-month period in Madagascar and Mauritius.
METHODS
A total of 198 patients with hypertension in ambulatory care who had been on fixed-dose combination of perindopril arginine, indapamide, and amlodipine for at least 4 weeks were included. The main outcome measures were changes in systolic and diastolic blood pressure, attainment of blood pressure control under 140/90 mmHg and 130/80 mmHg, self-reported drug tolerance by the patient, and perceived drug tolerance by the treating physician. Data was collected at 1 month and 3 months.
RESULTS
Mean systolic blood pressure was significantly lower at the 1-month (- 3.4 mmHg, p = 0.002) and 3-month (- 8.5 mmHg, p < 0.0001) visits. Diastolic blood pressure also decreased significantly (- 2.4 mmHg at 1-month, p = 0.017 and - 5.4 mmHg at the 3-month visits, p < 0.0001). At 3 months, 80.4% of the patients attained blood pressure targets less than 140/90 mmHg and 42.7% attained targets less than 130/80 mmHg on the basis of their baseline blood pressure. Excellent drug tolerance was reported by more than 90% of patients and physicians at the 1-month visit and by more than 95% at the 3-month visit.
CONCLUSION
Triple fixed-dose therapy of perindopril arginine/indapamide/amlodipine continues to show additional blood pressure-lowering capacity even months after initiating the treatment in patients with hypertension in Madagascar and Mauritius. It is also well tolerated by patients with hypertension and assessed as safe to use by physicians.
Topics: Amlodipine; Antihypertensive Agents; Arginine; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Humans; Hypertension; Indapamide; Madagascar; Mauritius; Perindopril; Treatment Outcome
PubMed: 35438448
DOI: 10.1007/s12325-022-02134-0 -
Archives of Cardiovascular Diseases May 2008Heart failure is a major public health problem. Heart failure with preserved systolic function (HF-PSF) is a common form, which is difficult to diagnose. Results of... (Review)
Review
Heart failure is a major public health problem. Heart failure with preserved systolic function (HF-PSF) is a common form, which is difficult to diagnose. Results of recent studies show that HF-PSF has a poor prognosis, with an annual survival rate similar to that of heart failure with left ventricular systolic dysfunction. Despite these findings, the therapeutic management of HF-PSF is not clearly defined. We will discuss in this review of the literature the current therapeutic management of HF-PSF, including the role of precipitating factors such as hypertension, myocardial ischaemia and supraventricular arrhythmias, and the main results of epidemiological registries and randomized controlled clinical trials in this disease. Only four large therapeutic trials have assessed the impact of different classes of drugs (digoxin, angiotensin II converting enzyme inhibitors, angiotensin II receptors type I blockers and beta-blockers) on morbidity and mortality in HF-PSF. Results of these trials are disappointing. Apart from the beta-blockers, the other three classes of drugs did not show benefit on the outcome of the disease. Moreover, the results of the beta-blocker trial are controversial as a mixed population of heart failure with and without preserved systolic function was studied. Finally, the current therapeutic management of patients with HF-PSF is still based on our pathophysiological knowledge: education, low salt diet, diuretics, slowing heart rate and controlling triggering factors. Other large randomized controlled multicenter trials, which may help us in the understanding of HF-PSP and its therapeutic management, are ongoing.
Topics: Adrenergic beta-Antagonists; Adult; Aged, 80 and over; Algorithms; Angiotensin-Converting Enzyme Inhibitors; Benzopyrans; Blood Pressure; Cardiotonic Agents; Digoxin; Ethanolamines; Heart Failure; Heart Rate; Humans; Hypertension; Myocardial Ischemia; Nebivolol; Perindopril; Randomized Controlled Trials as Topic; Registries; Renal Artery Obstruction; Systole; Treatment Outcome
PubMed: 18656095
DOI: 10.1016/j.acvd.2008.04.008 -
Turkish Journal of Medical Sciences Dec 2018This study aimed to investigate the effects of two different medical treatment options on choroidal thickness (CT) in patients with primary hypertension.
BACKGROUND/AIM
This study aimed to investigate the effects of two different medical treatment options on choroidal thickness (CT) in patients with primary hypertension.
MATERIALS AND METHODS
Forty newly diagnosed primary hypertension patients and 21 healthy volunteers were included. The patients were randomly divided into two subgroups. Group I started on perindopril arginine and Group II started on amlodipine. Submacular CT using optical coherence tomography (OCT) was measured before treatment and at the third and sixth months after treatment.
RESULTS
Initial mean arterial pressure (MAP) values in Groups I and II and the control group were 113.4, 109.8, and 89.4 mmHg, respectively, and mean CT values were 257.9, 286.5, and 300.9 μm. Mean MAP values in Groups I and II and the control group at the sixth month after treatment were 99.7, 99.6, and 90.2 mmHg, respectively, and mean CT values were 293.1, 286, and 297.4 μm. Analysis of the changes occurring during the study revealed significant variation in MAP in Groups I and II, and in CT in Group I only.
CONCLUSION
A gradual increase in CT developed with perindopril arginine therapy in patients with primary hypertension, while no significant change occurred in CT in the amlodipine group.
PubMed: 30541254
DOI: 10.3906/sag-1803-171 -
Annals of Medicine and Surgery (2012) Aug 2023Wunderlich syndrome is a rare and life-threatening condition that is characterized by spontaneous renal hemorrhage into the subcapsular and perinephric regions. This...
UNLABELLED
Wunderlich syndrome is a rare and life-threatening condition that is characterized by spontaneous renal hemorrhage into the subcapsular and perinephric regions. This case report describes the diagnosis and management of bilateral Wunderlich syndrome during pregnancy, resulting in Page kidney.
CASE PRESENTATION
The patient presented with complaints of left flank pain and breathlessness. After stabilization, an emergency lower cesarean delivery was performed, and a percutaneous drainage procedure was carried out to alleviate the compression on the left kidney. The patient was treated with blood transfusion, methyldopa, and perindopril. Follow-up examinations performed 3 months later revealed a significant decrease in fluid volume surrounding the left kidney.
CLINICAL DISCUSSION
Lenk's triad provides the primary description of the classical manifestations of this syndrome. Some instances have been connected to the Page kidney phenomenon. The relationship between pregnancy and Wunderlich syndrome has not been extensively studied, primarily because the symptoms can resemble other complications related to pregnancy. Due to the scarcity of evidence in the literature, there is no definitive guideline for managing Wunderlich syndrome during pregnancy. Consequently, each patient is treated on an individual basis. Conservative treatment is recommended once malignancy has been ruled out.
CONCLUSION
The case highlights the importance of considering Wunderlich syndrome as a differential diagnosis in pregnant patients with abdominal or flank pain, a palpable mass, and hypovolemia. Furthermore, the case illustrates the successful management of Wunderlich syndrome during pregnancy.
PubMed: 37554856
DOI: 10.1097/MS9.0000000000001062 -
Cardiology Research and Practice 2022Some antihypertensive medications alter cellular energy production, presumably by modification of the mitochondrial function. In vivo studies of such effects are...
BACKGROUND
Some antihypertensive medications alter cellular energy production, presumably by modification of the mitochondrial function. In vivo studies of such effects are challenging in humans. We applied a noninvasive forearm skin measurement of the 460-nm fluorescence specific for the reduced form of nicotinamide adenine dinucleotide (NADH) to study the 6-week effects of four different antihypertensive medications on mitochondrial function using the Flow-Mediated Skin Fluorescence (FMSF).
METHODS
In a prospective open-label study, we compared the long-term effects of a 6-week treatment with either amlodipine (5 mg), perindopril (5 mg), nebivolol (5 mg), or metoprolol (50 mg) on the dynamic flow-mediated changes in the skin NADH content in 76 patients (29 women) with untreated primary arterial hypertension (HA). Patients underwent 24-hour ambulatory blood pressure monitoring. To study mitochondrial function, the FMSF was measured at rest, during 100-second ischemia and postischemic reperfusion. The control group consisted of 18 healthy people (7 women).
RESULTS
There were no significant differences in the FMSF parameters between the control and the study group before medication. After the 6-week treatment, all drugs similarly reduced blood pressure. Neither amlodipine, perindopril, nor nebivolol changed the flow-mediated 460-nm skin fluorescence significantly. However, metoprolol raised this fluorescence at rest, during ischemia and reperfusion ( at most <0.05), indicating an increase in the total NADH skin content.
CONCLUSION
Amlodipine, perindopril, and nebivolol appear neutral for the skin NADH content during the 6-week antihypertensive treatment. Similar treatment with metoprolol increased skin NADH at rest, during ischemia and reperfusion, probably due to an effect on microcirculation and altered mitochondrial function. Explanation of the potential mechanisms behind metoprolol influence on the skin NADH metabolism requires further investigation.
PubMed: 35402043
DOI: 10.1155/2022/6159883 -
Cureus Aug 2021This review aimed to assess the efficacy and safety of once- versus twice-daily administration of angiotensin-converting enzyme (ACE) inhibitors for the management of... (Review)
Review
This review aimed to assess the efficacy and safety of once- versus twice-daily administration of angiotensin-converting enzyme (ACE) inhibitors for the management of hypertension. A literature search on PubMed and Google Scholar was performed (January 1980 to June 2020) using the following search terms: ACE inhibitors, lisinopril, enalapril, fosinopril, trandolapril, ramipril, perindopril, captopril, benazepril, ambulatory blood pressure, hypertension, twice-daily dosing, once-daily dosing. Reference lists from retrieved articles were examined for additional reports. Relevant English-language studies or those conducted in humans were considered. Overall, six studies were included that compared the efficacy of once-daily to twice-daily dosing of ACE inhibitors. Similar blood pressure-lowering effects, and, in some studies, greater blood pressure lowering has been noted in the twice-daily administration arm than once-daily administration of ACE inhibitors. ACE inhibitors' pharmacokinetic and pharmacodynamic properties play an integral role in determining the expected blood pressure-lowering outcome. It is noteworthy that adherence issues may arise when transitioning from a once-daily regimen to a twice-daily regimen. There appear to be no added safety concerns between twice-daily and once-daily administration of ACE inhibitors regarding safety outcomes. After reviewing the available literature, twice-daily dosing of ACE inhibitors may promote added blood pressure-lowering effects, with the advantages of reducing cost, reducing the risk of drug-drug interactions, reducing polypharmacy, and reducing patient confusion about their medications. Recommendations for twice-daily administration of ACE -inhibitors should be made via shared decision-making with the patient, and clinician judgment, to drive treatment selection.
PubMed: 34567875
DOI: 10.7759/cureus.17331