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1.
J Hypertens ; 42(8): 1373-1381, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38660708

RESUMO

BACKGROUND: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals. METHODS: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM). RESULTS: A total of 532 patients were randomized: Per/Ind/Aml ( n  = 262) and Per/Ind + Aml ( n  = 269). Overall, the mean (±SD) age was 55.7 ±â€Š8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ±â€Š14.46 mmHg Per/Ind/Aml versus -14.49 ±â€Š12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed ( P  < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated. CONCLUSIONS: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety.


Assuntos
Anlodipino , Anti-Hipertensivos , Hipertensão , Indapamida , Perindopril , Humanos , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Indapamida/administração & dosagem , Indapamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , Perindopril/administração & dosagem , Perindopril/uso terapêutico , Feminino , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Idoso , Resultado do Tratamento , Pressão Sanguínea/efeitos dos fármacos , China , Adulto , Combinação de Medicamentos , Quimioterapia Combinada , População do Leste Asiático
2.
J Hypertens ; 42(1): 136-142, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37728093

RESUMO

OBJECTIVES: This analysis compared adherence, cardiovascular (CV) events and all-cause mortality incidence, and healthcare costs among hypertensive patients treated with perindopril (PER)/indapamide (IND)/amlodipine (AML) in single-pill combination (SPC) vs. multiple-pill combination, in a real-world setting in Italy. METHODS: In this observational retrospective analysis of Italian administrative databases, adult patients treated with PER/IND/AML between 2010 and 2020 were divided into two cohorts: single-pill vs. multiple-pill. Patient data were available for at least one year before and after index date. Propensity score matching (PSM) was applied to reduce selection bias. Adherence was defined as proportion of days covered: non-adherence, <40%; partial adherence, 40-79%, and adherence ≥80%. Mortality incidence and CV events as single, or composite, endpoints were evaluated after first year of follow-up. Healthcare cost analyses were performed from the perspective of the Italian National Health Service. RESULTS: Following PSM, the single-pill cohort included 12 150 patients, and the multiple-pill cohort, 6105. The SPC cohort had a significantly higher percentage of adherent patients vs. the multiple-pill cohort (59.9% vs. 26.9%, P  < 0.001). Following the first year of follow-up, incidence of all-cause mortality, and combined endpoint of all-cause mortality and CV events were lower in the SPC cohort compared with multiple-pill cohort. Average annual direct healthcare costs were lower in the single-pill cohort (€2970) vs. multiple-pill cohort (€3642); cost of all drugs and all-cause hospitalizations were major contributors. CONCLUSION: The SPC of PER/IND/AML, compared with multiple-pill combination, is associated with higher adherence to medication, lower incidence of CV events and mortality, and reduced healthcare costs.


Assuntos
Hipertensão , Indapamida , Leucemia Mieloide Aguda , Adulto , Humanos , Perindopril/uso terapêutico , Indapamida/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Estudos Retrospectivos , Medicina Estatal , Adesão à Medicação , Anlodipino/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Combinação de Medicamentos , Custos de Cuidados de Saúde , Leucemia Mieloide Aguda/tratamento farmacológico
3.
Georgian Med News ; (343): 172-178, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38096536

RESUMO

Drug-induced Nitrosogenesis/Carcinogenesis turns out to be a ubiquitous, pervasive, large-scale, poorly controllable concept for the academic community, which underlies the long-term, permanent modification of the human genome by contact with nitrosamines/NDSRIs, which ultimately leads to the generation of diverse cancers, but also melanoma in particular. The discovery of a (currently) unclassifiable number of nitroso derivatives/genome modifiers in the most commonly distributed drugs worldwide (in about 300 preparations according to the FDA/includes beta blockers/bisoprolol/nebivolol and ACE inhibitors/perindopril), their forced tolerability, attributed as a necessity or lack of alternative also to the present (but also to future periods), and their proven carcinogenicity (already 70 years ago), suggest a kind of creepy form of experiment to which public health is subjected worldwide. The creation of a universal nitroso-comfort of pharmaceutical companies and the regulation of a permanent intake of carcinogens in drugs for years to come, but also decades back, suggest possible cartel agreements between the regulation/distribution unit and that of production cycles. These "agreements" are becoming increasingly evident and in all likelihood position nitrosogenesis from a until recently unknown element, to a pathogenetic factor of paramount importance. Melanoma could be viewed precisely as the controlled end gene-modified product of drug-mediated nitrosogenesis/carcinogenesis, proven to be a locoregional (but not only) phenomenon hundreds if not thousands of times. The dilemma stays: Are the nitrosamines in drugs genetic weapons, ethnic bioweapons for silent war ? The nitrosogenesis concerning melanoma leads to the logical conclusion that cancer is in fact a largely controlled set event or, according to others, a forced necessity of evolutionary globalization processes to purge the population in certain regions. In favor of this statement indicative are namely: 1) lack of regulatory control/results of such conducted, 2) complete information veil for the end user regarding contamination with carcinogens/nitrosamines in certain batches or all batches of drugs, 3) misinformation and lack of transparency regarding the concept of nitrosogenesis also for the academic community, as well as 4) the impunity to pharmaceutical conglomerates after criminal negligence/controlled criminogenicity proven thousands of times by the FDA/EMA leading to regulatory controlled drug mediated genocide of the human population in certain areas on a daily basis. And most important of all: 5) the lack of refusal to eliminate these drugs, i.e. - the imposition of forced tolerance at any cost. It is extremely unfortunate that the mentioned and identified grotesque/situation, its tolerance on a global scale, lead to a misjudgement of the significance of real tumor inducers within the global health map//statistics as well as melanoma. The focus of prevention is being displaced, while the incidence of cancer in general and that of melanoma is skyrocketing. Nitrosamines could be defined as the newest, modern, until recently invisible and unknown, but -controllable form of genetic weapon to modify the human genome. Because of these very facts, the likelihood that clinicians and the academic community are in the frozen and permanent state of the Dunning-Kruger effect is very real. Certain globalization regulatory elements create problems and assignments that must be solved ˝competently˝ by incompetent, fully regulatable compartments. As their state of competence depends again and entirely on ˝their incompetence˝. Until now. After the formalization of the concept of Nitrosogenesis (as a form of genetic weapon) and melanoma for example, but not only, it remains to be seen whether universal incompetence will become a guarantee of competence and the survival. Or- will it remain again at the level of globalized, criminally conditioned, appointed and regulated from above "competent incompetence". The dilemmas to regulators and manufacturers remain open : Is it competent to take drugs that contain carcinogens/nitrosamines? Is it competent for this issue to continue for decades with impunity? Is it competent for regulators not to inform consumers about the presence of carcinogens/genome modifiers in medicines for decades? Is it competent for certain regions to be affected by nitrosamine contamination and not others? Is it competent not to reflect this in regional and global health bulletins on side effects? Is it competent to make thousands of times the profits from the modified genetic map business, regulated and legally initiated through the intake of carcinogens? Is it competent to have the concentration of carcinogens within polymedication exceeding many times the daily allowable doses of carcinogens and have no solution for this? Is it competent, when the intake of nitrosamines in medicines is associated with the generation of melanomas and heterogeneous cancers- to have no alternative to this or when one is available- to conceal it skillfully? Is it competent to determine carcinogenic activity based on mutagenic tests? Is it competent to be polyincompetent within a framework of mass (in)competence? We report systemically administered drugs for the treatment of high blood pressure from the group of beta blockers (bisoprolol/nebivolol) and ACE inhibitors (perindopril) that have been identified by regulators in the face of FDA as hypothetically contaminated with nitrosamines/NDSRIs with a carcinogenic potency between 4 and 5, respectively. Within this cumulative intake, (which according to the regulators was not at risk of developing cancerous forms), similar to other cases in the world literature, the patient developed a relatively short-term, metastatic nevus spilus-based nodular melanoma. The paper analyses not only the role of nitrosogenesis, but also that of two pregnancies and painful sunburns as potential cofactors for melanoma genesis. Academic attention is drawn to the potential impact of drug-mediated nitrosogenesis/carcinogenesis. Nitrosamines in the framework of polycontamination and polymedication could also be identified as one of the most effective, until recently unknown, modern generation genetic weapons for modifying the human genome and controlling cancer. Moreover, they could be controllably applied and skillfully targeted. At least until now. The officialization of carcinogens in more than 250 of the most common drugs and the clinico-pathological correlations concerning the development of cancer/melanoma in poorly controlled geographical regions represent a kind of in vivo prospective study to determine precisely the real carcinogenic role of nitrosamines to date.


Assuntos
Melanoma , Nevo , Nitrosaminas , Neoplasias Cutâneas , Humanos , Melanoma/induzido quimicamente , Melanoma/genética , Perindopril , Bisoprolol , Nebivolol , Inibidores da Enzima Conversora de Angiotensina , Estudos Prospectivos , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/genética , Carcinógenos , Nitrosaminas/toxicidade , Carcinogênese/genética , Antagonistas Adrenérgicos beta , Preparações Farmacêuticas
4.
Georgian Med News ; (339): 24-32, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37522769

RESUMO

The Nitrosogenesis of skin cancer is a newly introduced concept in medical science, the significance of which is yet to be the subject of detailed analyses and discussions. Contamination of the most commonly used drugs for systemic treatment worldwide (such as Angiotensin receptor II blockers/ARBs, ACE inhibitors, Beta blockers, Thiazide diuretics, Metformin, Ranitidine, Nizatidine, tricyclic antidepressants, anticoagulants/dabigatran, Rifampicin, calcium channel blockers, SSRIs/ selective serotonin reuptake inhibitors, Varenicline) is already a fact and is more than worrying but also indicative. It is "this relationship" that has been repeatedly described in the medical literature (initially) as an association, and subsequently now increasingly as a causal relationship, a pathogenetic relationship. Observational data from clinicians over the past year increasingly speak in favour of a pathogenetic link and associate every single drug declared as contaminated with the development of heterogeneous forms of skin cancer gradually and surely. New drugs are added monthly that have not yet been declared as actually/potentially contaminated but are probably known to regulatory authorities or are in the process of being clarified. In parallel, the number of nitrosamines identified as contaminants in medicines is growing. This should not be surprising to anyone: ˝You take 3 drugs contaminated with mutagens- you subsequently develop skin cancer˝. Polymorbidity and multimedication against the background of polycontamination with nitrosamines appears to be the most serious problem at present. While until recently polymorbidity was considered to be a key factor in carcinogenesis (generator, trigger, inducer), today this dogma should be re-examined or looked at from another, radically different angle: from the angle of polycontamination to multimedication within polymorbidity. It is this that could provide a good explanation for the pandemic concerning skin cancer, for example. The development of relatively identical patterns of manifestation of skin tumors after concomitant intake of drugs declared as contaminated (drugs from the classes already mentioned above/ with radically different mechanism of action) supports unequivocally the thesis that: the nitrosogenesis of skin cancer is an undeniable fact that should be studied in detail. Studied because it could be eliminated. The analysis presented within this scientific thesis concerns 4 polymorbid patients who developed skin tumors within the framework of the multimedication they were assigned. The concomitant intake of medications declared as contaminated (in the presented patients) led to the manifestation of single or multiple skin neoplasms that were successfully treated surgically. Once again, the importance of potential/actual contamination of beta blockers, ACE inhibitors, oral antidiabetic drugs, and sartans in the generation of 1) non-melanocytic forms of skin cancer, and 2) melanoma precursor lesions or so-called dysplastic moles is established and validated. The possible contamination with nitrosamines of 1) other types of tricyclic antidepressant- Melitracen; 2) antidepressant of the selective serotonin reuptake inhibitor (SSRI) class: Paroxetine; 3) antidepressant of the serotonin and noradrenaline reuptake inhibitor (SNRIs) class: Venlafaxine, as well as of the systemic anticoagulant: apixaban is highlighted for the first time in the world literature.


Assuntos
Metformina , Inibidores da Recaptação de Serotonina e Norepinefrina , Neoplasias Cutâneas , Humanos , Inibidores Seletivos de Recaptação de Serotonina , Inibidores da Enzima Conversora de Angiotensina , Bloqueadores do Receptor Tipo 1 de Angiotensina II , Bloqueadores dos Canais de Cálcio , Bisoprolol , Cloridrato de Venlafaxina , Paroxetina , Enalapril , Antidepressivos Tricíclicos , Perindopril , Losartan , Anlodipino , Valsartana , Antagonistas de Receptores de Angiotensina , Incidência , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico
5.
Georgian Med News ; (337): 138-145, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37354687

RESUMO

The problem of contamination of the most commonly used medicines with nitrosamines is worsening worldwide. According to recent literature data, this "contamination" is the cause not only of skin cancer (keratinocytic/melanoma) but also of gastrointestinal neoplasms, brain tumours, neuroblastoma, rectal carcinoma, acute lymphoblastic leukaemia, and many others. It is these clinical manifestations that are associated with/ or already directly linked to the nitrosamine content of drugs and food products used by patients in previous periods. And it is this permissive availability/contamination that could prove to be the most likely, powerful inducer of acquired mutations underlying the worldwide cancer pandemic. Of further concern is the evidence of contamination of newer classes of medications by nitrosamines- namely: beta blockers, calcium antagonists and selective serotonin reuptake inhibitors (SSRIs). In practice, mankind faces the problem of certainly over 1 billion patients taking nitrosamine-contaminated drugs: 280 million patients with depression (antidepressants), over 1 billion patients with arterial hypertension (antihypertensive drugs), over half a billion patients with type 2 diabetes mellitus (oral antidiabetic drugs/metformin/ sitagliptin), over 4 billion patients with gastritis (ranitidine), over 5 million with tuberculosis (rifampicin), and probably a number of others. The calculations are apocalyptic, since even if only 20-30% of the groups were affected, the number of patients taking these drugs would, by a rough calculation, currently amount to over 1 billion. And there are certainly other classes of drugs yet to be announced. It is for this reason that we should not be surprised that the data on the development of keratinocyte cancer after intake of nitrosamine-contaminated preparations is growing at a breakneck pace. This data indirectly but strongly confirms the importance of a newly introduced concept in the medical science : Nitrosogenesis of skin cancer. A concept, until recently unknown, incomprehensible, but at the same time frightening and gradually accepted, imposing itself and which with each passing day is gaining more and more scientific significance and "visibility", "scientific tangibility, receptivity, and acceptability." This article presents, for the first time in the world literature, patients who developed single/multiple forms of keratinocytic cancer (partly in combination with melanoma precursors-dysplastic moles) after administration of two new classes of potentially nitrosamine-contaminated antihypertensive drugs: beta blockers (bisoprolol, metoprolol) and calcium antagonists (amlodipine, felodipine). For the first time in the scientific literature, the contributory pro-carcinogenic role of another potentially nitrosamine-contaminated ACE inhibitor- lisinopril , as well as that of candesartan: in the development of keratinocytic cancer is also discussed. For the first time in the world literature, the conclusion regarding the pathogenetic relationship between the intake of potentially contaminated drugs (from different drug groups) and cancer development is based on the model of the equivalent clinical manifestation of skin tumors (rather than on controlled long-term prospective analyses). Nitrosamine contamination in these drug groups appears to be the sole and major unifying factor or causative agent for these manifestations.


Assuntos
Diabetes Mellitus Tipo 2 , Melanoma , Nitrosaminas , Neoplasias Cutâneas , Humanos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina , Anlodipino , Perindopril , Metoprolol , Bisoprolol , Bloqueadores do Receptor Tipo 1 de Angiotensina II , Lisinopril , Felodipino , Inibidores de Simportadores de Cloreto de Sódio , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nitrosaminas/efeitos adversos , Estudos Prospectivos , Cálcio , Tiazidas
6.
Luminescence ; 38(9): 1583-1590, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37325939

RESUMO

A spectrofluorimetric approach that is sensitive, simple, validated, and cost-effective has been proposed for the estimation of amlodipine (AML) and perindopril (PER) in their bulk powders, pharmaceutical formulations, and spiked human plasma. The recommended approach utilized the quantitative quenching effect of the two cited drugs on the fluorescence intensity of erythrosine B, as a result of complex binary reactions among each drug with erythrosine B at pH 3.5 (Teorell and Stenhagen buffer). The quenching of erythrosine B fluorescence was recorded at 554 nm after excitation at 527 nm. The calibration curve was detected in the range 0.25-3.0 µg ml-1 , with a correlation coefficient of 0.9996 for AML, and 0.1-1.5 µg ml-1 , with a correlation coefficient of 0.9996 for PER. The established spectrofluorimetric approach was validated for the estimation of the cited drugs with high sensitivity regarding International Council on Harmonization guidelines. Therefore, the established approach could be utilized for quality control of the cited drugs in their pharmaceutical formulations.


Assuntos
Anlodipino , Leucemia Mieloide Aguda , Humanos , Perindopril , Eritrosina , Espectrometria de Fluorescência , Preparações Farmacêuticas
7.
Georgian Med News ; (336): 123-125, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37166894

RESUMO

Contamination of certain drugs and foods with one of the most potent carcinogens/mutagens- nitrosamines, remains to be an issue and unresolved at present. The increased contamination of these mutagens in the most commonly used drugs in the human population doesn't ceases to baffle clinicians, critics, public scholars, and analysts of the nitrosamine saga. The introduction of permissive determinations of the presence of carcinogens in drugs only reinforces doubts about the powerlessness of regulatory authorities in the face of the influence of powerful pharmaceutical cartels. The FDA's encouraging promises of 2018 for strict control of carcinogens in sartans seems to have been permanently forgotten? By 2021, it was unthinkable that these carcinogens would be present in blood drugs and affected batches were immediately removed. Following alert checks confirming their post-existence in diabetes drugs, anti-smoking drugs, a number of antibiotics, ACE inhibitors, Sartans, thiazide diuretics, ranitidine, but probably a number of others, the decision has been taken to give the green light to their permissible availability. An availability that in all likelihood has the flavour of death. A "flavour" that has been confirmed in hundreds of international publications. Or in data from scientific papers submitted to regulatory regional units for verification and which remain sadly silent to this day. The "silent confirmation" and the lack of any adequate response in favour of public health are a sufficient further indicator of the attitude and position of the regulatory authorities. A position that should be changed. Starting from the mentioned facts and the data announced already in 2016/2017 of all-American data shared originally in American scientific journals, using their statistical estimates, we present the first case in the world literature of nodular melanoma and basal cell carcinoma occurring after taking perindopril. This intake turns out to be confirmatory one with respect to the statistics presented by Beatrice Nardone dating back to 2017. The potential pro-carcinogenic effects of both nitrosamines and the generic substance of perindopril are discussed.


Assuntos
Melanoma , Nitrosaminas , Neoplasias Cutâneas , Humanos , Nitrosaminas/toxicidade , Perindopril , Bloqueadores do Receptor Tipo 1 de Angiotensina II , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Melanoma/patologia , Carcinógenos , Mutagênicos/toxicidade , Aromatizantes
8.
Georgian Med News ; (335): 90-94, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37042596

RESUMO

Nitrosamines as contaminants in a wide variety of drugs are also found to be one of the most likely causes of skin cancer. A detailed analysis of this contamination could in the near future solve to a large extent the puzzle of carcinogenesis concerning the keratinocytic forms of cancer and melanoma. But also, probably cancer in general. Over 80% of skin cancer is due to acquired mutations, and nitrosamines, which are contained as contamination in certain batches of the most commonly distributed drugs worldwide (such as sartans, ACE inhibitors, ranitidine, metformin, hydrochlorothiazide, rifampicin, and a number of others.) are considered among the most powerful external mutagens, carcinogens. Carcinogens that until 2021 were not supposed to be present in medicines and carcinogens for which it was subsequently decided to create a regulatory regime for permissible availability. Regardless of whether these contaminants are applied within the so-called daily acceptable intake dose or many times above it, the problem with the availability of nitrosamines continues to be present. It is also caused by the lack of reflection of the concentration of the corresponding nitrosamine in a certain drug. Thus, it is impossible to calculate the ˝permissible daily intake of the total number of mutagens and their concentration based on polymedication˝. In practice, drug manufacturers distribute nitrosamines in parallel with drugs, although they are not listed as a component of the product but are identified and allowed as contamination or substances with permissible availability by the EMA/FDA. From another point of view, the fact that is not commented on is also of interest, namely that not all batches are affected by this contamination. This suggests that the contamination may have been controlled, since in a manufacturing error the contamination should be widespread. The registration of the potential contamination of a heterogeneous type of medicinal products on the European market to the executive agencies for drug control in certain geographical areas has remained for years without any answer and opens a number of questions. The problem with ACE inhibitors is similar to that with sartans, hydrochlorothiazide, metformin, and ranitidine. The ˝special impression˝ of the clinicians is determined by the fact that the patterns of manifestation of the skin tumors during the administration of a heterogeneous class of medications are similar to completely identical. From this it could be concluded that the unifying factor between the pattern of occurrence could not be based on the action of the main substance of each drug class, since it remains to be radically different. The unifying link remains the sole and only contamination or the permissible already availability of a new ingredient known as nitrosamines. We present cases of multiple basal cell carcinomas and dysplastic nevi following enalapril and perindopril administration. The role of potential contamination of ACE inhibitors with nitrosamines for the development of skin cancer is discussed.


Assuntos
Síndrome do Nevo Displásico , Nitrosaminas , Neoplasias Cutâneas , Humanos , Nitrosaminas/análise , Inibidores da Enzima Conversora de Angiotensina , Perindopril , Enalapril , Bloqueadores do Receptor Tipo 1 de Angiotensina II , Ranitidina , Carcinógenos/análise , Preparações Farmacêuticas , Hidroclorotiazida , Mutagênicos
9.
Adv Ther ; 40(4): 1765-1772, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36829102

RESUMO

INTRODUCTION: Single-pill combination therapy for hypertension is recognized to improve adherence to treatment. However, less is known about the benefits of triple single-pill combinations. This retrospective observational analysis aimed to assess changes in adherence when treatment was switched from perindopril (PER)/indapamide (IND) + amlodipine (AML) to PER/IND/AML single-pill combination, in Italian clinical practice. METHODS: This analysis used data extracted from administrative databases of Italian healthcare entities. Adult patients receiving PER/IND/AML were selected, and the prescription date was considered as the index date. Among them, those who had a prescription for PER/IND + AML during the 12 months before the index date and a prescription of PER/IND/AML during 6 months of follow-up were included. Adherence was calculated as the proportion of days covered (PDC: PDC < 40%, non-adherent; PDC = 40-79%, partially adherent; PDC ≥ 80%, adherent). RESULTS: Among the identified patients, 158 were exposed users and were included in the analysis. When patients were compared before and after switch to triple single-pill combination, the proportion of adherent patients was significantly higher with PER/IND/AML single-pill combination (75.3%) than with PER/IND + AML combination (44.3%) (P < 0.05). Conversely, the proportion of non-adherent patients was lower with the PER/IND/AML single-pill combination (14.6%) vs PER/IND + AML (17.7%) (P < 0.001). CONCLUSION: This real-world analysis showed that switching to a triple single-pill combination could offer an opportunity to improve adherence to antihypertensive treatment in real-life clinical practice.


Medication adherence is defined by the World Health Organization as the "extent to which a person's behavior (in taking medication) corresponds with agreed recommendations from a healthcare provider". Low levels of medication adherence in hypertension have been linked with increased disease burden and with higher costs for patients. Patients with hypertension whose blood pressure is poorly controlled often need to receive more than one pill. Nevertheless, having to take many pills may result in poor adherence, i.e., patients not taking their treatment as prescribed. Combining multiple drugs into a single pill for the management of hypertension is known to improve adherence; however, limited evidence exists about the benefits of triple single-pill combinations compared with equivalent free combinations in real clinical practice. This analysis evaluated changes in adherence before and after patients switched from a three-drug therapy of perindopril/indapamide single-pill + amlodipine (PER/IND + AML) to perindopril/indapamide/amlodipine (PER/IND/AML) taken as a single pill. In this analysis, real-world data from Italian administrative databases covering around 11% of the Italian population were used. Overall, 158 patients were included. More patients were found to be adherent after switch to PER/IND/AML single pill (75.3% vs 44.3% of PER/IND + AML combination). Partially adherent and poorly adherent patients were fewer with PER/IND/AML single-pill combination (10.1% and 14.6%, respectively) compared to PER/IND + AML combination (38.0% and 17.7%, respectively). These findings indicate that switching to a simplified therapy in which all three drugs are taken in one pill may offer an opportunity for increasing the number of patients that are adherent to their medication.


Assuntos
Hipertensão , Indapamida , Leucemia Mieloide Aguda , Adulto , Humanos , Anlodipino/uso terapêutico , Perindopril/uso terapêutico , Indapamida/uso terapêutico , Estudos Retrospectivos , Pressão Sanguínea , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Combinação de Medicamentos , Adesão à Medicação , Leucemia Mieloide Aguda/tratamento farmacológico
10.
Mayo Clin Proc ; 97(10): 1808-1823, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36202494

RESUMO

OBJECTIVE: To synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). METHODS: PubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI. RESULTS: Thirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, -0.54 [95% CI, -0.88 to -0.21]; P=.002; I2=96%), IL-6 (WMD, -0.84 [95% CI, -1.03 to -0.64]; P<.001; I2=0%), and TNF-α (WMD, -12.75 [95% CI, -17.20 to -8.29]; P<.001; I2=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, -1.34 [95% CI, -2.65 to -0.04]; P=.04; I2=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, -1.07 to -0.27]; P=.001; I2=94%) and in patients with coronary artery disease (WMD, -0.75 [95% CI, -1.17 to -0.33]; P<.001; I2=96%). CONCLUSION: Based on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.


Assuntos
Interleucina-6 , Fator de Necrose Tumoral alfa , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Inflamatórios , Anti-Hipertensivos/uso terapêutico , Biomarcadores , Proteína C-Reativa/análise , Enalapril , Humanos , Perindopril , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema Renina-Angiotensina
11.
Curr Oncol ; 29(5): 2941-2953, 2022 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-35621631

RESUMO

BACKGROUND: Two anti-cancer agents, doxorubicin (DOX) and trastuzumab (TRZ), are commonly used in the management of breast cancer in women. Despite their efficacy in reducing the morbidity and mortality of individuals with breast cancer, the use of these agents is limited by adverse cardiotoxic side effects. Both the nutraceutical agent flaxseed (FLX) and the pharmaceutical drug perindopril (PER) have been studied individually in the prevention of chemotherapy-mediated cardiac dysfunction. The objective of this study was to determine whether the prophylactic administration of FLX is comparable and/or synergistic with PER in preventing DOX + TRZ-induced cardiotoxicity. METHODS: Over a six-week period, 81 wild-type C57Bl/6 female mice (8-12 weeks old) were randomized to receive regular chow (RC) or 10% FLX-supplemented diets with or without PER (3 mg/kg/week; oral gavage). Starting at week 4, mice were randomized to receive a weekly injection of saline or DOX (8 mg/kg) + TRZ (3 mg/kg). Serial echocardiography was conducted weekly and histological and biochemical analyses were performed at the end of the study. RESULTS: In mice treated with RC + DOX + TRZ, left ventricular ejection (LVEF) decreased from 75 ± 2% at baseline to 37 ± 3% at week 6. However, prophylactic treatment with either FLX, PER, or FLX + PER partially preserved left ventricular systolic function with LVEF values of 61 ± 2%, 62 ± 2%, and 64 ± 2%, respectively. The administration of FLX, PER, or FLX + PER was also partially cardioprotective in preserving cardiomyocyte integrity and attenuating the expression of the inflammatory biomarker NF-κB due to DOX + TRZ administration. CONCLUSION: FLX was equivalent to PER at preventing DOX + TRZ-induced cardiotoxicity in a chronic in vivo murine model.


Assuntos
Neoplasias da Mama , Cardiotoxicidade , Linho , Perindopril , Animais , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Doxorrubicina/toxicidade , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Perindopril/uso terapêutico , Trastuzumab/toxicidade
12.
J Biochem Mol Toxicol ; 36(8): e23080, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35417068

RESUMO

Mortality rates associated with myocardial dysfunction due to sepsis and septic shock are generally high across the world. The present study focused on the antioxidant and anti-inflammatory effects of perindopril (PER) for the purpose of preventing the adverse effects of sepsis on the myocardium and developing new alternatives in treatment. The control group received only saline solution via the oral route for 4 days. The second group underwent cecal ligation puncture (CLP), and the third underwent CLP and received PER (2 mg/kg). Rats in the third group received 2 mg/kg PER per oral (p.o.) from 4 days before induction of sepsis. Thiobarbituric acid reactive species (TBARS), total thiol (-SH), interleukin-1 beta (IL-1ß), IL-6, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κB/p65) levels increased in the CLP groups. In contrast, PER (2 mg/kg) decreased the levels of biochemical parameters other than total-SH and decreased 8-OHdG, NF-κB/p65 immunopositivity in rat heart tissues. The data from this study show that impairment of the oxidant/antioxidant balance and inflammatory cytokine levels in favor of inflammation in heart tissue under septic conditions results in severe tissue damage. PER administration before sepsis was shown to exhibit antioxidant and anti-inflammatory properties by reducing these effects. This in turn increased the importance of PER as new evidence of its protective effects in heart tissue.


Assuntos
NF-kappa B , Sepse , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Oxigênio , Perindopril/farmacologia , Perindopril/uso terapêutico , Ratos , Ratos Sprague-Dawley , Sepse/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo
13.
Am J Cardiovasc Drugs ; 22(2): 219-230, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35257306

RESUMO

The single-pill combination (SPC) of perindopril (PER)/indapamide (IND)/amlodipine (AML) is a valuable and convenient treatment option for patients with hypertension controlled with two-drug SPC of PER/IND + AML given as two separate pills at the same dose level. PER [an angiotensin-converting enzyme (ACE) inhibitor], IND (a thiazide-like diuretic) and AML (a calcium channel blocker) are well established antihypertensive agents, which have been available for a long time as monotherapies and dual SPCs and have complementary mechanisms of action. Once-daily PER/IND/AML provided effective BP control, with good tolerability, in patients with uncontrolled hypertension in clinical trials and in large observational prospective studies. The efficacy and tolerability of PER/IND/AML was similar to that of PER/IND + AML in a randomized clinical trial. The therapeutic effect of PER/IND/AML was associated with improved health-related quality of life. Thus, switching from the two-pill PER/IND + AML regimen to single-pill PER/IND/AML reduces pill burden and simplifies drug administration, which may improve adherence to treatment, leading to better BP control and clinical outcomes.


Approximately one-quarter of patients with hypertension require three antihypertensive agents to achieve BP control. However, complex treatment regimens and high pill burden reduce treatment adherence, which in turn leads to poor BP control. Perindopril (PER), indapamide (IND), amlodipine (AML) belong to the core drug classes for the treatment of hypertension. These drugs have been available for a long time as monotherapies and two-drug single-pill combinations. Once-daily PER/IND/AML provides very good BP control in patients with uncontrolled hypertension and is generally well tolerated. The single-pill PER/IND/AML has similar efficacy and tolerability to PER/IND + AML given as two separate pills. Therefore, switching from PER/IND + AML to PER/IND/AML reduces pill burden and simplifies the treatment regimen, which may improve adherence to treatment, leading to better BP control and clinical outcomes. Thus, PER/IND/AML is a valuable and convenient treatment option for patients with hypertension controlled with PER/IND + AML at the same dose level.


Assuntos
Hipertensão , Indapamida , Anlodipino/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Combinação de Medicamentos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Indapamida/efeitos adversos , Perindopril/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
J Cachexia Sarcopenia Muscle ; 13(2): 858-871, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35174663

RESUMO

BACKGROUND: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. METHODS: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between-group difference in the short physical performance battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy. RESULTS: We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect -0.1 points (95%CI -1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.4 kg (95%CI -1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI -1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between-group difference -0.1 points (95%CI -0.4 to 0.2)]. CONCLUSIONS: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.


Assuntos
Leucina , Perindopril , Desempenho Físico Funcional , Sarcopenia , Idoso , Feminino , Força da Mão/fisiologia , Humanos , Leucina/uso terapêutico , Masculino , Metanálise como Assunto , Perindopril/uso terapêutico , Sarcopenia/tratamento farmacológico , Sarcopenia/fisiopatologia , Resultado do Tratamento
15.
Drug Chem Toxicol ; 45(6): 2509-2518, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34384315

RESUMO

Indomethacin is a widely used nonsteroidal anti-inflammatory drug; however, its clinical utility is accompanied by serious adverse reactions including peptic ulcers. The current study aims to investigate the protective potential of perindopril against indomethacin-induced gastric injury in rats. Perindopril (4 mg/kg) was administered orally for 7 days and indomethacin (60 mg/kg, single oral dose) was administered on the 7th day, 1 h after perindopril administration. Pantoprazole was used as a standard agent. Ulcer index (UI), preventive index ratio (PI), histopathological examination, oxidative stress, and inflammatory biomarkers were investigated. Perindopril significantly decreased UI while increased PI and counteracted histopathological aberrations induced by indomethacin. It alleviated indomethacin-induced oxidative stress by lowering NO while increasing GSH content and superoxide dismutase activity. Perindopril significantly downregulated TNF-α and asymmetric dimethylarginine (ADMA), while significantly upregulated COX-2, PGE-2, dimethylarginine dimethylaminohydrolase-1 (DDAH-1), ANG-(1-7), and ACE-2 expression. Together, these findings suggest the gastroprotective effects of perindopril through modulation of DDAH-1/ADMA and ACE-2/ANG-(1-7) signaling.HIGHLIGHTSPerindopril attenuated gastric histopathological damage.It increased GSH content and SOD activity while decreased NO content.It modulated gastric ADMA and DDAH-1 activity.It reduced TNF-α, while increased COX-2 and PGE-2 expression.It upregulated ACE-2 activity and ANG-(1-7) protein expression.


Assuntos
Indometacina , Perindopril , Ratos , Animais , Indometacina/toxicidade , Perindopril/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Pantoprazol , Ciclo-Oxigenase 2 , Transdução de Sinais , Anti-Inflamatórios não Esteroides , Superóxido Dismutase/metabolismo , Biomarcadores , Prostaglandinas E
16.
Chem Biol Interact ; 351: 109732, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34737150

RESUMO

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-1ß, 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.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Enteropatias/tratamento farmacológico , Perindopril/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Enteropatias/induzido quimicamente , Intestinos/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Metotrexato , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Perindopril/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Sirtuína 1/metabolismo , Receptor 4 Toll-Like/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-34092792

RESUMO

AIMS: Sub-analysis of a retrospective nation-wide observational analysis of heart failure (HF) epidemiology reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018 aimed at angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II-receptor antagonists (ARB) and angiotensin receptor blocker/neprilysin inhibitor (ARNI) use. METHODS AND RESULTS: ACEi and ARBs were generally used in 87.6% of all HF patients in 2012 (n=154 627); 84.5% in 2013 (n=170 861); 83.5% in 2014 (n=186 963); 81.6% in 2015 (n=198 844); 80.1% in 2016 (n=205 793); 78.0% in 2017 (n=212 152) and in 76.7% in 2018 (n=219 235). In a sub-analysis of patients with a medical procedure and/or examination using an I50.x ICD code accounted for in the given year, ACEi and ARBs were generally used in 99.3% in 2012 (n=63 250); 96% in 2013 (n=62 241); 95.2% in 2014 (n=64 414); 93.3% in 2015 (n=65 217); 91.8% in 2016 (n=65 236); 90.1% in 2017 (n=65 761) and in 88.6% in 2018 (n=66 332). In 2018, the majority of patients with HF were prescribed ramipril (n=49 909; 17.5%) and perindopril (n=44 332; 15.5%). The mostly prescribed ARBs in 2018 were telmisartan (n=18 669; 6.5%); losartan (n=13 935; 4.9%) and valsartan (n=4 849; 1.7%). In 24.5% of cases, ACEIs and ARBs were prescribed in a fixed combination with another drug. ARNI became gradually more prescribed from 2018 (n=9 659 in November 2020). CONCLUSION: In an analysis of ACEIs, ARBs and ARNIs utilization in all patients treated for heart failure in the given year in the whole country, we found a comparable rate of drug prescription in comparison with specific heart failure registries. This indicates a good translation of current standard of care into common clinical practice. Ramipril and perindopril remained the mostly prescribed ACEIs and telmisartan became the mostly prescribed ARB. Since 2018, ARNIs began to be widely prescribed.


Assuntos
Antagonistas de Receptores de Angiotensina , Insuficiência Cardíaca , Bloqueadores do Receptor Tipo 2 de Angiotensina II/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Angiotensinas/uso terapêutico , Anti-Hipertensivos , República Tcheca/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Humanos , Losartan/uso terapêutico , Neprilisina/uso terapêutico , Perindopril/uso terapêutico , Ramipril/uso terapêutico , Estudos Retrospectivos , Telmisartan/uso terapêutico , Valsartana/uso terapêutico
18.
Clin Sci (Lond) ; 136(1): 139-161, 2022 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-34878093

RESUMO

Angiotensin-converting enzyme inhibitors (ACEis) have been used to treat anthracycline (ANT)-induced cardiac dysfunction, and they appear beneficial for secondary prevention in high-risk patients. However, it remains unclear whether they truly prevent ANT-induced cardiac damage and provide long-lasting cardioprotection. The present study aimed to examine the cardioprotective effects of perindopril on chronic ANT cardiotoxicity in a rabbit model previously validated with the cardioprotective agent dexrazoxane (DEX) with focus on post-treatment follow-up (FU). Chronic cardiotoxicity was induced by daunorubicin (DAU; 3 mg/kg/week for 10 weeks). Perindopril (0.05 mg/kg/day) was administered before and throughout chronic DAU treatment. After the completion of treatment, significant benefits were observed in perindopril co-treated animals, particularly full prevention of DAU-induced mortality and prevention or significant reductions in cardiac dysfunction, plasma cardiac troponin T (cTnT) levels, morphological damage, and most of the myocardial molecular alterations. However, these benefits significantly waned during 3 weeks of drug-free FU, which was not salvageable by administering a higher perindopril dose. In the longer (10-week) FU period, further worsening of left ventricular function and morphological damage occurred together with heart failure (HF)-related mortality. Continued perindopril treatment in the FU period did not reverse this trend but prevented HF-related mortality and reduced the severity of the progression of cardiac damage. These findings contrasted with the robust long-lasting protection observed previously for DEX in the same model. Hence, in the present study, perindopril provided only temporary control of ANT cardiotoxicity development, which may be associated with the lack of effects on ANT-induced and topoisomerase II ß (TOP2B)-dependent DNA damage responses in the heart.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Cardiotoxicidade/prevenção & controle , Daunorrubicina/efeitos adversos , Perindopril/uso terapêutico , Animais , Antibióticos Antineoplásicos , Cardiotoxicidade/tratamento farmacológico , Cardiopatias/induzido quimicamente , Cardiopatias/prevenção & controle , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Masculino , Coelhos , Troponina T/sangue
19.
Braz. J. Pharm. Sci. (Online) ; 58: e20012, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1394034

RESUMO

Abstract Perindopril erbumine (Perindopril tert-butylamine salt) is a potent angiotensin-converting enzyme (ACE) inhibitor. It is used to treat the patients with hypertension and heart failure problems. A sensitive, inexpensive and precise analytical technique has been developed for the estimation of perindopril in bulk and formulations. The procedure involves the development of colour by forming an oxidative coupling reaction between drug (PPE) and reagent such as 2, 6-dichloroquinone-4-chlorimide (DCQC). The formed colored species were measured at (max=520 nm. The developed method showed linearity within the concentration limits of 25-75 µg mL-1. The linear correlation coefficient (r) and molar absorptivity were found to be 0.9999 and 3.285 x 103 mol-1cm-1. % Recovery ± SD values were in the range of 99.69 - 100.51 (+ 0.42 - ( 0.41) (n=3) which indicates the accuracy of the developed method. The interference of other excipients that are commonly present in formulations is found to be negligible. Precision and accuracy of the proposed method were confirmed by student t-test and F-tests at 95% confidence limits with (n-1) degrees of freedom. The validity parameters of proposed method were calculated by ICH guidelines


Assuntos
Perindopril , Acoplamento Oxidativo , Espectrofotometria/métodos , Angiotensinas/administração & dosagem , Preparações Farmacêuticas , Química Farmacêutica/classificação , Insuficiência Cardíaca
20.
Medicine (Baltimore) ; 100(42): e27572, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34678898

RESUMO

RATIONALE: Neurofibromatosis type 1 (NF-1) is an autosomal-dominant neurocutaneous disorder that affects the skin, bones, and nervous system. The most common manifestation of kidney involvement is renal artery stenosis; glomerulonephritis is extremely rare. In this case report, we present a patient with NF-1 and immunoglobulin A nephropathy (IgAN). PATIENT CONCERNS: A 51-year-old Korean man previously diagnosed with NF-1 presented with persistent proteinuria and hematuria identified during a routine medical check-up. He had no history of hypertension or diabetes, and denied a history of alcohol use or smoking. DIAGNOSIS: The contrast-enhanced computed tomography scan revealed normal-sized kidneys and no evidence of renal artery stenosis. On the day of the kidney biopsy, laboratory tests showed a serum creatinine level of 1.1 mg/dL, urine protein/creatinine ratio of 1.3 g/g, and urine red blood cell count of >10 to 15/HPF. The kidney biopsy sample revealed IgAN grade III, according to Lee glomerular grading system. INTERVENTION: The patient was advised to take 4 mg of perindopril. OUTCOME: Three months after the treatment, the urine protein/creatinine ratio decreased to 0.6 g/g, with no change in the serum creatinine level (1.03 mg/dL). LESSONS: A genetic link between NF-1 and IgAN or other glomerular diseases is not established. However, activation of the mTOR pathway may explain this association.


Assuntos
Glomerulonefrite por IGA/complicações , Neurofibromatose 1/complicações , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Perindopril/uso terapêutico
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