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1.
Blood Press ; 31(1): 58-63, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35438025

RESUMO

PURPOSE: The aim of our study was to evaluate the adherence to mineralocorticoid receptor (MR) antagonists and other antihypertensive therapy and blood pressure control in conservatively treated patients with primary aldosteronism (PA). MATERIALS AND METHODS: Conservatively treated subjects with previously confirmed PA (n-50, 64.5 ± 9 years of age, 24% women) were investigated via our outpatient hypertension clinic. All subjects underwent regular examinations in our clinic. In addition to basic laboratory and clinical parameters, 24 h ambulatory blood pressure monitoring (ABPM) (Spacelabs) was evaluated. Unplanned blood sampling for assessment of serum antihypertensive drug concentrations by the means of liquid chromatography-mass spectrometry was performed in all patients. In case of spironolactone, its active metabolite canrenone was also evaluated. Total non-compliance was then defined as the absence of all measured antihypertensive drugs. Partial non-compliance was calculated as the absence of serum levels of at least one, but not all antihypertensive drugs prescribed. RESULTS: Good blood pressure control was detected (mean 24 h systolic/diastolic BP 130 ± 12/77 ± 9 mmHg). The average number of antihypertensive drugs was 3.9 ± 1.5. All subjects were treated by MR antagonists. 44% of patients received spironolactone (average daily dose 45 ± 20 mg) and in the remaining 56% of subjects eplerenone was administered (average daily dose 80 ± 30 mg) due to spironolactone side effects. Assessment of antihypertensive drug concentrations revealed full adherence in 80% of all subjects, partial nonadherence was noted in the remaining 20% of subjects. MR antagonist levels were detected in almost all subjects (49 out of 50). CONCLUSIONS: Good blood pressure control and adherence to therapy were detected in conservatively treated patients with PA. Eplerenone had to be used quite often as male subjects did not tolerate dose escalation due to spironolactone side effects.


Assuntos
Hiperaldosteronismo , Hipertensão , Idoso , Anti-Hipertensivos , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Eplerenona/farmacologia , Eplerenona/uso terapêutico , Feminino , Humanos , Hiperaldosteronismo/tratamento farmacológico , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona/uso terapêutico
2.
Turk J Ophthalmol ; 52(2): 147-152, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35481737

RESUMO

The aim of this case report is to describe a case of atypical central serous chorioretinopathy (CSCR) definitively diagnosed after 8 years. A 44-year-old woman presented with reduced visual acuity in her left eye. Her visual acuity was light perception with projection in the right eye and 0.15 in the left. She described a similar decline in vision in her right eye 8 years ago. At that time, she had exudative retinal detachment and was treated with systemic immunosuppressive therapy for a presumed diagnosis of Vogt-Koyanagi-Harada disease. Despite resolution of the exudative retinal detachment, macular scarring developed. Eight years later, she developed inferior exudative retinal detachment in the left eye. A diagnosis of atypical CSCR was made with the help of multimodal imaging and her left eye was successfully treated with eplerenone and half-fluence photodynamic therapy (hf-PDT). In conclusion, early diagnosis and treatment of atypical CSCR may prevent subretinal fibrosis formation and permanent vision loss. Hf-PDT and eplerenone are successful treatment options for atypical CSCR.


Assuntos
Coriorretinopatia Serosa Central , Fotoquimioterapia , Descolamento Retiniano , Síndrome Uveomeningoencefálica , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/tratamento farmacológico , Criança , Eplerenona/uso terapêutico , Feminino , Humanos , Descolamento Retiniano/etiologia , Síndrome Uveomeningoencefálica/complicações , Síndrome Uveomeningoencefálica/diagnóstico , Síndrome Uveomeningoencefálica/tratamento farmacológico
3.
Sci Rep ; 12(1): 4727, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35304566

RESUMO

To compare the anatomical/functional changes after navigated subthreshold pulse laser (SML) and oral eplerenone therapy for chronic central serous chorioretinopathy (cCSC). A total of 36 eyes of 36 patients suffering from cCSC treated with navigated SML (Navilas® 577s; OD-OS GmbH, near Berlin, Germany) (18 eyes, SML group) and oral eplerenone (18 eyes, eplerenone group) were enrolled in this retrospective study. Main outcome measures during a 3-month follow up period included changes of best corrected visual acuity (BCVA), central macular thickness (CMT), foveal subretinal fluid thickness (FSRFT), and subfoveal choroidal thickness (SFCT). At baseline average duration of symptoms was 6.8 ± 0.6 months in SML group and 6.4 ± 0.9 months in eplerenone group (p = 0.127). Mean BCVA, CMT and FSRFT changed significantly over time (p < 0.001). From baseline to 90 days the BCVA improved from 0.3 ± 0.1 to 0.1 ± 0.1 logMAR in SML group and from 0.3 ± 0. to 0.2 ± 0.1 logMAR in eplerenone group, CMT reduced from 357.1 ± 104.3 to 210.6 ± 46.7 µm and from 428.7 ± 107.7 to 332.5 ± 27.5 µm in SML group and eplerenone group respectively, FSRFT reduced from 144.4 ± 108.2 to 22.6 ± 37.2 µm and from 217.1 ± 105.9 to 54.4 ± 86.2 µm in SML group and eplerenone group. 55.6% of patients in SML group and 66.7% in eplerenone group showed a complete resolution of FSRFT during follow up. The interaction between group and time was statistically significant with greater absolute variation for CMT and FSRFT in SML group compared to eplerenone group (p < 0.001 and p = 0.043). SFCT did not change significantly during follow up (p = 0.083) for both groups. Both navigated SML and oral eplerenone were effective treatments showing recovery of retinal morphology and related visual acuity improvement in cCSC.


Assuntos
Coriorretinopatia Serosa Central , Coriorretinopatia Serosa Central/tratamento farmacológico , Coriorretinopatia Serosa Central/cirurgia , Doença Crônica , Eplerenona , Angiofluoresceinografia , Humanos , Lasers , Retina , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento
4.
PLoS One ; 17(3): e0265642, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35324976

RESUMO

Diabetic nephropathy (DN), which is correlated with an increased risk of cardiovascular disease, significantly elevates the morbidity and mortality of patients with diabetes. Recently, the benefits of mineralocorticoid receptor antagonists in chronic kidney disease (CKD), such as their anti-inflammatory and anti-fibrotic properties, have been discovered. Thus, the present meta-analysis aimed to systematically assess the efficacy and safety of eplerenone treatment in patients with DN. Six electronic databases-PubMed, The Cochrane Library, Embase, Web of Science, CNKI (China National Knowledge Infrastructure), and CBM(Chinese BioMedical Literature Database)-were searched to retrieve randomized controlled trials that assessed eplerenone treatment in patients with DN and were published up to July 31, 2021. Eight randomized controlled trials involving 838 patients were included. Between the eplerenone treatment groups and controls, significant differences were identified in 24-h urine protein levels (mean difference [MD], -19.63 [95% CI, -23.73 to -15.53], P < 0.00001), microalbuminuria (MD, -7.75 [95% CI, -9.75 to -5.75], P < 0.00001), urinary albumin-creatinine ratio (MD, -48.29 [95% CI, -64.45 to -32.14], P < 0.00001), systolic blood pressure (SBP) (MD, -2.49 [95% CI, -4.48 to -0.50], P = 0.01), serum potassium levels (MD, 0.19 [95% CI, 0.13 to 0.24], P < 0.00001), and levels of the renal fibrosis indicator laminin (MD, -8.84 [95% CI, -11.93 to -5.75], P < 0.00001). However, for the effect of estimated glomerular filtration rate (MD, 1.74 [95% CI, -0.87 to 4.35], P = 0.19) and diastolic blood pressure (MD, -0.51 [95% CI, -1.58 to 0.57], P = 0.36), the differences between the two groups were not significant. In addition, no noticeable difference was identified in the adverse events of hyperkalemia and cough between them. These findings suggest that eplerenone exerts beneficial effects on DN by significantly reducing urinary albumin or protein excretion, SBP, and laminin levels, without increasing the incidence of hyperkalemia and other adverse events.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Hiperpotassemia , Albuminas , Nefropatias Diabéticas/tratamento farmacológico , Eplerenona/uso terapêutico , Feminino , Humanos , Laminina , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Eur J Intern Med ; 97: 86-94, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35000806

RESUMO

AIMS: In the absence of previous direct comparative studies, we aimed to evaluate the effectiveness of spironolactone and eplerenone in patients with heart failure and reduced ejection fraction (HFrEF) in a real-world clinical setting. METHODS: Using Fine-Gray´s competing risk regression, we compared the clinical outcomes of 293 patients with chronic HF and left ventricular ejection fraction <40% treated with eplerenone and 293 propensity-score matched individuals treated with spironolactone. Study subjects were selected from a prospective cohort of 1404 ambulatory patients with HFrEF seen since 2010 to 2019 in a single specialized HF clinic, among which 992 received a mineralocorticoid receptor antagonist at baseline. Median follow-up was 3.95 years. RESULTS: No statistically significant differences between patients treated with eplerenone versus spironolactone were observed with regard to the risk of the primary composite end-point cardiovascular death or HF hospitalization (HR 0.95; 95% CI 0.73-1.23; p= 0.677). However, eplerenone use was associated to lower cardiovascular mortality (HR 0.55; 95% CI 0.35-0.85; p= 0.008) and lower all-cause mortality (HR 0.67; 95% CI 0.47-0.95; p= 0.027). The incidence of drug suspension due to side effects (HR 0.58, 95% CI 0.40-0.85; p= 0.005) and drug suspension due to any reason (HR 0.70, 95% CI 0.51-0.97; p= 0.033) were lower among patients treated with eplerenone. CONCLUSIONS: In this observational, real-world, propensity-score matched study of patients with HFrEF, eplerenone was associated to lower cardiovascular mortality and lower all-cause mortality than spironolactone.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Eplerenona/farmacologia , Eplerenona/uso terapêutico , Humanos , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Estudos Prospectivos , Espironolactona/uso terapêutico , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
6.
Eur Heart J Cardiovasc Pharmacother ; 8(2): 108-117, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33175088

RESUMO

AIMS: A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated. METHODS AND RESULTS: In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (i) patients aged 20 years or older and (ii) those with left ventricular ejection fraction of ≤40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group [hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855]. In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure within 6 months was 0.55 (95% CI: 0.213-1.434). The safety profile for eplerenone was as expected. CONCLUSION: The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.


Assuntos
Insuficiência Cardíaca , Espironolactona , Idoso , Eplerenona/efeitos adversos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Espironolactona/efeitos adversos , Volume Sistólico , Função Ventricular Esquerda
7.
Pharmacology ; 107(1-2): 35-45, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34879385

RESUMO

INTRODUCTION: The study sought to assess the effect of treatment with mineralocorticoid receptor antagonists (MRAs) on long-term prognosis of patients with systolic heart failure (HF) surviving index episodes of ventricular tachyarrhythmias. METHODS: A large retrospective registry was used including consecutive HF patients with left ventricular ejection fraction <45% and index episodes of ventricular tachyarrhythmias from 2002 to 2015. The primary endpoint was all-cause mortality at 3 years and secondary endpoints were rehospitalization, as well as the composite endpoint consisting of recurrent ventricular tachyarrhythmias, sudden cardiac death and appropriate implantabe cardioverter defibrillator (ICD) therapies at 3 years. RESULTS: 748 patients were included, 20% treated with MRA and 80% without. At 3 years, treatment with MRA was not associated with improved all-cause mortality (22% vs. 24%, log-rank p = 0.968; hazard ratio (HR) = 1.008; 95% CI 0.690-1.472; p = 0.968). Accordingly, risk of the composite endpoint (28% vs. 27%; HR = 1.131; 95% CI 0.806-1.589; p = 0.476) and first cardiac rehospitalization (24% vs. 22%; HR = 1.139; 95% CI 0.788-1.648; p = 0.489) were not affected by treatment with MRA. CONCLUSION: In patients with ventricular tachyarrhythmias, treatment with MRA was not associated with improved all-cause mortality at 3 years. The therapeutic effect of MRA treatment in patients with ventricular tachyarrhythmias needs to be reinvestigated within further randomized controlled trials.


Assuntos
Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Taquicardia Ventricular/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Eplerenona/farmacologia , Eplerenona/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Espironolactona/farmacologia , Espironolactona/uso terapêutico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/mortalidade , Adulto Jovem
8.
Pediatr Transplant ; 26(2): e14191, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34806263

RESUMO

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) predisposes patients for risk of recurrent disease in allografts. METHODS: We report a case of a recipient of an unrelated living donor renal transplant and discuss considerations for utilization of ofatumumab and eplerenone in treatment for recurrent FSGS. RESULTS: The recipient was initially managed with scheduled plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab post-transplant during index hospitalization. With notable recurrence of FSGS noted on kidney transplant biopsy, she was initially treated with additional plasmapheresis sessions leading to downtrend in proteinuria. The patient was then transitioned to LDL-A pheresis, which resulted again in uptrend in proteinuria. This prompted return to scheduled plasmapheresis sessions weekly, leading again to a downtrend in proteinuria. Albumin levels remained within normal range throughout her course. Following initiation of eplerenone and ofatumumab, the patient demonstrated normalization of urine protein:creatinine ratio and remission of FSGS recurrence without need for additional apheresis. CONCLUSIONS: With notable risk of recurrence of FSGS in kidney transplants leading to allograft failure, the use of ofatumumab and eplerenone in conjunction should be considered for management to induce remission.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Eplerenona/uso terapêutico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Transplante de Rim , Adolescente , Quimioterapia Combinada , Feminino , Glomerulosclerose Segmentar e Focal/cirurgia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Plasmaferese , Recidiva
9.
Clin Res Cardiol ; 111(4): 380-392, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33893561

RESUMO

BACKGROUND: Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were eplerenone exhibits some of its pleotropic effects. Little is known about the effect of eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF. METHODS: The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium < 135 mmol/L or > 145 mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization. RESULTS: A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to eplerenone had a lower mean serum sodium over the follow-up (140 vs 141 mmol/L; p < 0.0001) and more often developed hyponatremia episodes (15 vs 11% p = 0.0001) and less often hypernatremia episodes (22 vs. 26% p = 0.0003). Hyponatremia, but not hypernatremia was associated with adverse outcome for all outcome endpoints in the placebo group but not in the eplerenone group (interaction p value < 0.05 for all). Baseline sodium values did not influence the treatment effect of eplerenone in reducing the various endpoints (interaction p value > 0.05 for all). Development of new-onset hyponatremia following eplerenone initiation did not diminish the beneficial eplerenone treatment effect. CONCLUSION: Eplerenone induces minor reductions in serum sodium. The beneficial effect of eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing eplerenone to patients who had an MI complicated with LVSD and/or HF. TRAIL REGISTRY: ClinicalTrials.gov identifier: NCT00232180. Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Disfunção Ventricular Esquerda , Eplerenona/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Sódio , Resultado do Tratamento
10.
Am J Ophthalmol ; 233: 101-110, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34214454

RESUMO

PURPOSE: To compare the efficacy and safety between half-dose photodynamic therapy (PDT) and eplerenone therapy for treating chronic central serous chorioretinopathy (cCSC). DESIGN: This was a multicenter, open-label, randomized controlled trial. METHODS: This investigator-initiated trial was conducted in 3 academic medical centers in the Netherlands. Eligible patients were randomized at a 1:1 ratio to receive either indocyanine green angiography-guided half-dose PDT or oral eplerenone for 12 weeks. Both anatomical and functional outcomes were evaluated at 3 months after the start of treatment. RESULTS: A total of 107 patients were randomly assigned to receive either half-dose PDT (n = 53) or eplerenone treatment (n = 54). Thirteen patients (3 in the PDT group and 10 in the eplerenone group) did not adhere to the study protocol. At the 3-month evaluation visit, 78% of patients in the PDT group had complete resolution of subretinal fluid accumulation compared to only 17% of patients in the eplerenone group (P < .001). Mean best-corrected visual acuity in Early Treatment of Diabetic Retinopathy Study letters at the 3-month evaluation visit was 83.7 ± 10.8 and 82.8 ± 9.0 in the PDT and eplerenone groups, respectively (P = .555). In addition, mean retinal sensitivity on microperimetry was 25.4 ± 3.4 dB and 23.9 ± 4.0 dB in the PDT and eplerenone groups, respectively (P = .041). Finally, mean vision-related quality of life scores were 87.2 ± 8.5 and 83.8 ± 12.1 in the PDT and eplerenone groups, respectively (P = .094). Three patients (6%) in the PDT group experienced adverse events during the study compared to 18 patients (33%) in the eplerenone group. CONCLUSIONS: Half-dose PDT is superior to oral eplerenone for cCSC with respect to both short-term safety and efficacy outcomes.


Assuntos
Coriorretinopatia Serosa Central , Fotoquimioterapia , Porfirinas , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/tratamento farmacológico , Doença Crônica , Eplerenona/uso terapêutico , Angiofluoresceinografia , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Qualidade de Vida , Tomografia de Coerência Óptica , Resultado do Tratamento , Verteporfina/uso terapêutico , Acuidade Visual
11.
J Steroid Biochem Mol Biol ; 215: 106024, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34774724

RESUMO

Aldosterone, the main physiological mineralocorticoid in humans and other terrestrial vertebrates, first appears in lungfish, which are lobe-finned fish that are forerunners of terrestrial vertebrates. Aldosterone activation of the MR regulates internal homeostasis of water, sodium and potassium, which was critical in the conquest of land by vertebrates. We studied transcriptional activation of the slender African lungfish MR by aldosterone, other corticosteroids and progesterone and find that aldosterone, 11-deoxycorticosterone, 11-deoxycortisol and progesterone have half-maximal responses (EC50 s) below 1 nM and are potential physiological mineralocorticoids. In contrast, EC50 s for corticosterone and cortisol were 23 nM and 66 nM, respectively. Unexpectedly, truncated lungfish MR, consisting of the DNA-binding, hinge and steroid-binding domains, had a stronger response to corticosteroids and progesterone than full-length lungfish MR, indicating that the N-terminal domain represses steroid activation of lungfish MR, unlike human MR in which the N-terminal domain contains an activation function. BLAST searches of GenBank did not retrieve a GR ortholog, leading us to test dexamethasone and triamcinolone for activation of lungfish MR. At 10 nM, both synthetic glucocorticoids are about 4-fold stronger than 10 nM aldosterone in activating full-length lungfish MR, leading us to propose that lungfish MR also functions as a GR.


Assuntos
Aldosterona/farmacologia , Dexametasona/farmacologia , Proteínas de Peixes/genética , Peixes/genética , Receptores de Glucocorticoides/genética , Receptores de Mineralocorticoides/genética , Animais , Corticosterona/farmacologia , Cortodoxona/farmacologia , Desoxicorticosterona/farmacologia , Eplerenona/farmacologia , Proteínas de Peixes/agonistas , Proteínas de Peixes/metabolismo , Peixes/metabolismo , Expressão Gênica , Hidrocortisona/farmacologia , Cinética , Progesterona/farmacologia , Domínios Proteicos , Engenharia de Proteínas/métodos , Receptores de Glucocorticoides/agonistas , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/agonistas , Receptores de Mineralocorticoides/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Espironolactona/farmacologia , Triancinolona/farmacologia
13.
J UOEH ; 43(4): 379-384, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34897166

RESUMO

Primary aldosteronism (PA) is associated with a high risk of cardiovascular complications. Large-scale clinical studies have demonstrated that mineralocorticoid receptor antagonists (MRA) exhibit organ-protective effects and improve the prognosis of patients with heart failure and myocardial infarction, and daily clinical practice suggests that MRA seem to improve vascular endothelial dysfunction. In this pilot study, we treated 10 PA patients with eplerenone for 3 months. We used Endo-PAT to evaluate the effects of MRA on vascular endothelial function and analyzed the data for correlative factors. The primary outcome measure, the reactive hyperemia index (RHI), was 1.71 before therapy and increased significantly to 2.21. Univariate analysis showed a significant correlation between the rate of change in RHI and that in plasma renin activity (PRA). Since plasma aldosterone concentration increases during MRA therapy, PRA may be the best marker for selecting the most appropriate dose of MRA. PRA can potentially be used for adjusting the dose of MRA, in addition to adjusting blood pressure and serum potassium level.


Assuntos
Hiperaldosteronismo , Hipertensão , Eplerenona , Humanos , Hiperaldosteronismo/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Projetos Piloto
14.
Wiad Lek ; 74(9 cz 1): 2087-2093, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34725281

RESUMO

OBJECTIVE: The aim: To increase the treatment effectiveness of CHF patients after MI with stenting by using magnesium and potassium salts of gluconic acid, eplerenone, and rivaroxaban in complex therapy. PATIENTS AND METHODS: Materials and methods: The research was performed at the premises of Ivano-Frankivsk Regional Clinical Cardiology Centre, Ukraine. 84 patients with CHF after past MI were examined. RESULTS: Results and conclusions: A more pronounced anti-ischemic effect has been linked to the use of combination therapy with rivaroxaban on the background of basic therapy (BT) in patients with CHF after MI, compared with the use of magnesium and potassium salts of gluconic acid or eplerenone. The use of eplerenone in the complex treatment of these patients on the background of BT has been proven to provide a pronounced reverse remodeling of the left myocardium in the postinfarction period.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Eplerenona , Gluconatos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Magnésio , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Miocárdio , Potássio , Rivaroxabana/uso terapêutico , Sais , Espironolactona/uso terapêutico
15.
Drug Deliv ; 28(1): 2510-2524, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34842018

RESUMO

Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bioavailability after oral administration. In this study, we aimed to develop and evaluate eplerenone nanocrystals (EPL-NCs) for solubility and dissolution enhancement. D-optimal combined mixture process using Design-Expert software was employed to generate different combinations for optimization. EPL-NCs were prepared by a bottom-up, controlled crystallization technique during freeze-drying. The optimized EPL-NCs were evaluated for their size, morphology, thermal behavior, crystalline structure, saturation solubility, dissolution profile, in vivo pharmacokinetics, and acute toxicity. The optimized EPL-NCs showed mean particle size of 46.8 nm. Scanning electron microscopy revealed the formation of elongated parallelepiped shaped NCs. DSC and PXRD analysis confirmed the crystalline structure and the absence of any polymorphic transition in EPL-NCs. Furthermore, EPL-NCs demonstrated a 17-fold prompt increase in the saturation solubility of EPL (8.96 vs. 155.85 µg/mL). The dissolution rate was also significantly higher as indicated by ∼95% dissolution from EPL-NCs in 10 min compared to only 29% from EPL powder. EPL-NCs improved the oral bioavailability as indicated by higher AUC, Cmax, and lower Tmax than EPL powder. Acute oral toxicity study showed that EPL-NCs do not pose any toxicity concern to the blood and vital organs. Consequently, NCs prepared by controlled crystallization technique present a promising strategy to improve solubility profile, dissolution velocity and bioavailability of poorly water-soluble drugs.


Assuntos
Anti-Hipertensivos/farmacocinética , Eplerenona/farmacocinética , Nanopartículas/química , Administração Oral , Animais , Anti-Hipertensivos/administração & dosagem , Área Sob a Curva , Peso Corporal , Varredura Diferencial de Calorimetria , Química Farmacêutica , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Eplerenona/administração & dosagem , Liofilização , Masculino , Taxa de Depuração Metabólica , Camundongos , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Solubilidade , Difração de Raios X
16.
Lima; IETSI; nov. 2021.
Não convencional em Espanhol | BRISA/RedTESA, BRISA/RedTESA | ID: biblio-1357708

RESUMO

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de eplerenona como tratamiento en pacientes con insuficiencia cardíaca crónica con fracción de eyección reducida < 35 %, clase funcional NYHA II-IV y con terapia óptima, que desarrollan ginecomastia con mastodinia debido a uso de espironolactona. La insuficiencia cardiaca (IC) es un conjunto de síntomas y signos que resultan de anormalidades estructurales y/o funcionales de la función cardiaca y que conducen a un gasto cardiaco reducido o altas presiones de llenado al reposo o con esfuerzo. Se clasifica según la fracción de eyección del ventrículo izquierdo (FEVI) como IC con fracción de eyección reducida (ICFEr) o IC con fracción de eyección preservada (ICFEp). La ICFEr tiene una FEVI < 40 %. Todos los pacientes con ICFEr clase NYHA II-IV deben iniciar tratamiento con un inhibidor de la enzima convertidora de angiotensina (IECA) o un bloqueador del receptor de la angiotensina II (ARA II), y un beta bloqueador (BB). Se debe agregar a este esquema un antagonista de los receptores de mineralocorticoides (ARM). El ARM disponible en EsSalud es la espironolactona. Sin embargo, algunos pacientes pueden sufrir el evento adverso de ginecomastia con dolor mamario con su uso, afectando de manera negativa las actividades diarias y la calidad de vida. Según opinión de los especialistas en cardiología, esta situación podría impactar también en la adherencia al tratamiento. OBJETIVO: evaluar la eficacia y seguridad de eplerenona como tratamiento en pacientes con insuficiencia cardiaca crónica con FEVI < 35 %, clase funcional NYHA II-IV y con terapia óptima, que desarrollan ginecomastia con mastodinia debido a uso de espironolactona. METODOLOGÍA: La búsqueda de la literatura científica se realizó con el objetivo de identificar evidencia sobre eplerenona en el tratamiento de los pacientes con insuficiencia cardiaca crónica con fracción de eyección reducida < 35 %, clase funcional NYHA II-IV y con terapia óptima, que desarrollan ginecomastia con mastodinia debido a uso de espironolactona. La búsqueda de la literatura científica identificó tres GPC (ESC 2021, NICE 2018 y SIGN 2016) y cuatro ensayos clínicos aleatorizados (ECA); tres de ellos fueron controlados con placebo y uno comparó eplerenona con espironolactona. Los tres primeros fueron el estudio RALES que evaluó a espironolactona, el estudio EMPHASIS-HF que evaluó a eplerenona y el estudio J-EMPHASIS-HF que evaluó la eplerenona. El cuarto ensayo comparó espironolactona con eplerenona (Khondokar 2020). RESULTADOS: Se llevó a cabo una búsqueda de evidencia científica relacionada al uso de eplerenona como tratamiento en pacientes con IC crónica con FEVI < 35 %, clase funcional NYHA II-IV y con terapia óptima, que desarrollan ginecomastia con mastodinia debido a uso de espironolactona. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA fase III). CONCLUSIONES: En el presente documento, se evaluó la mejor evidencia científica disponible hasta la actualidad en relación con la eficacia y seguridad de eplerenona como tratamiento en pacientes con insuficiencia cardiaca crónica con fracción de eyección reducida < 35%, clase funcional NYHA II-IV y con terapia óptima, que desarrollan ginecomastia con mastodinia debido a uso de espironolactona. La eplerenona ejerce su acción al unirse a los receptores de mineralocorticoides y de esta manera impide su unión a la aldosterona. Eplerenona está contraindicado en los pacientes con: 1) Potasio > 5.5 mEq/L al inicio, 2) Depuración de creatinina ≤ 30 mL/min. Una diferencia importante con la espironolactona es la alta selectividad que tiene eplerenona por los receptores de aldosterona. La introducción del grupo epoxi presente en la eplerenona afecta solo marginalmente su afinidad por los receptores de mineralocorticoides, pero disminuye su afinidad por los receptores de andrógenos y progesterona tres a diez veces menor que el de aldosterona. Todas las guías clínicas consultadas recomiendan agregar un ARM como la espironolactona o eplerenona, al tratamiento óptimo con BB y IECA/ARAII, en pacientes con ICFEr, clase funcional NYHA II-IV, para mejorar su sobrevida. Además, las GPC recomiendan que los clínicos deben considerar cambiar a eplerenona en pacientes que experimentan ginecomastia tomando espironolactona, pero este cambio debe ser considerado como parte de una toma de decisiones compartida, ya que la valoración en evitar la aparición de ginecomastia varia de paciente a paciente. El primer ARM fue espironolactona y fue estudiado en el ECA de Pitt et 1999 (RALES), que evaluó los efectos de agregar espironolactona al régimen recomendado en pacientes con ICFEr y síntomas moderados a severos (clase funcional NYHA III o IV). Comparado con placebo, la adición de espironolactona al régimen de primera línea disminuyó la tasa de muerte por cualquier causa y el riesgo de hospitalización por causas cardiovasculares, comparado con placebo. Posteriormente, se desarrolló otro ARM: eplerenona que fue comparado con placebo en el estudio EMPHASIS-HF, el cual incluyó a pacientes menos sintomáticos (NYHA II) con tratamiento óptimo. La eplerenona redujo el riesgo de muerte por cualquier causa y la hospitalización total, comparado con placebo. Por lo expuesto, el IETSI aprueba el uso de eplerenona como tratamiento en pacientes con insuficiencia cardiaca crónica con FEVI < 35 %, clase funcional NYHA II-IV y con terapia optima, que desarrollan ginecomastia con mastodinia debido a uso de espironolactona. La vigencia del presente dictamen es de dos años, según lo establecido en el Anexo N° 1 y la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.


Assuntos
Humanos , Espironolactona/farmacologia , Mastodinia/fisiopatologia , Eplerenona/uso terapêutico , Ginecomastia/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Eficácia , Análise Custo-Benefício
17.
Pharmacotherapy ; 41(12): 998-1008, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34655484

RESUMO

BACKGROUND: Mineralocorticoid receptor antagonist (MRA) when combined with either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may provide additional benefits of cardiovascular and kidney disease risk reduction in patients with diabetic kidney disease (DKD) and hypertension. We evaluated the effectiveness of combination therapy (MRAs, either spironolactone or eplerenone, plus ACEI/ARB) compared with monotherapy (ACEI/ARB only) in patients with DKD and hypertension. METHODS: Retrospective cohort study was performed in patients (age ≥ 18 years) with hypertension, diabetes, and albuminuria between 2008 and 2018 within an integrated health system. MRA with ACEI/ARB compared to ACEI/ARB alone was evaluated on composite of cardiovascular events, progression to end-stage kidney disease, or all-cause mortality. Hyperkalemia was compared as a safety outcome. RESULTS: We identified 1282 patients who received MRAs with ACEI/ARBs and 5484 patients who received ACEI/ARBs alone. Median exposure time for combination therapy was 126 days. The rates per 100 person-years of cardiovascular, kidney, or all-cause mortality outcomes were 12.2 and 9.2 for combination therapy and monotherapy, respectively (hazard ratios = 1.24, 95% Confidence Interval (CI):0.94, 1.63). Patients receiving combination therapy had greater reduction in urine albumin-to-creatinine ratio compared with monotherapy (Mean reduction: 823 and 585 mg/g; p < 0.001, respectively). Hyperkalemia was more frequent in combination therapy versus monotherapy (22.3 vs. 10.9 per 100 person-years for combination and monotherapy, respectively; hazard ratios = 1.78, 95%CI: 1.42, 2.24). CONCLUSIONS: Among patients with DKD and hypertension, the short-term use of MRAs, either spironolactone or eplerenone, in combination with ACEI/ARBs, was not associated with lower risk of cardiovascular or kidney outcomes compared with ACEI/ARB monotherapy. The risk of hyperkalemia and the short duration of combination therapy may suggest a real-world clinical challenge for MRA with ACEI/ARB combination therapy.


Assuntos
Nefropatias Diabéticas , Hipertensão , Adolescente , Adulto , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/epidemiologia , Quimioterapia Combinada/efeitos adversos , Eplerenona/efeitos adversos , Eplerenona/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Nefropatias/epidemiologia , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Estudos Retrospectivos , Espironolactona/efeitos adversos , Espironolactona/uso terapêutico , Resultado do Tratamento
18.
Physiol Rep ; 9(15): e14971, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34350730

RESUMO

Individuals with type 2 diabetes have an increased risk of cardiovascular disease. A correlation between plasma aldosterone and hyperinsulinemia has been demonstrated in vivo, and hyperinsulinemia and insulin resistance are independently associated with the development of cardiovascular complications. We investigated if mineralocorticoid blockade (Eplerenone) improves insulin sensitivity in individuals with type 2 diabetes compared to healthy controls. We included 13 participants with type 2 diabetes (<5 years; male/female, Caucasians) and 10 healthy control participants (male/female, Caucasians). On 2 experimental days, before and at the end of the 8 weeks of treatment with mineralocorticoid blockade, a two-stage hyperinsulinemic-isoglycemic clamp (20 and 50 mU∙m-2 min-1 ) was performed for the determination of insulin sensitivity. No change in insulin sensitivity was detected at the end of the mineralocorticoid blockade in the individuals with type 2 diabetes or the healthy controls. Both before and at the end of the treatment with mineralocorticoid blockade, the individuals with type 2 diabetes had a lower insulin sensitivity compared to healthy controls. In conclusion, mineralocorticoid receptor blockade does not appear to improve insulin sensitivity in individuals with type 2 diabetes. CLINICAL TRIAL REGISTRATION: NCT03017703. https://clinicaltrials.gov/ct2/show/NCT03017703.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Eplerenona/uso terapêutico , Resistência à Insulina , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Receptores de Mineralocorticoides/química , Glicemia/análise , Estudos de Casos e Controles , Feminino , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade
19.
Int J Nanomedicine ; 16: 4985-5002, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335024

RESUMO

BACKGROUND: Eplerenone (Epl) is a selective mineralocorticoid-receptor antagonist used for chronic central serous chorioretinopathy treatment. Our goal was to enhance the corneal performance of Epl-loaded nanostructured lipid carriers (NLCs) through surface modification using different coating polymers. METHODS: Epl-loaded modified NLCs (Epl-loaded MNLCs) were prepared by coating the surface of Epl-loaded NLCs using different polymers, namely hyaluronic acid, chitosan oligosaccharide lactate, and hydrogenated collagen. A 31×41 full factorial design was used to evaluate the effect of the surface modification on the properties of the prepared systems. Selected optimal Epl-loaded MNLCs were further evaluated for in vitro drug release, morphology, pH, rheological properties, corneal mucoadhesion, irritation, and penetration. RESULTS: Epl-loaded MNLCs were successfully prepared with high drug-entrapment efficiency and nanosized particles with low size distribution. Transmission electron microscopy revealed nanosized spherical particles surrounded by a coating layer of the surface modifier. The pH, refractive index, and viscosity results of the Epl-loaded MNLCs confirmed the ocular compatibility of the systems with no blurring of vision. The safety and ocular tolerance of the optimal MNLCs were confirmed using the hen's egg test on chorioallantoic membrane and by histopathological evaluation of rabbit eyes treated with the optimal systems. Confocal laser-scanning microscopy of corneal surfaces confirmed successful transcorneal permeation of the Epl-loaded MNLCs compared to the unmodified Epl-loaded NLCs, revealed by higher corneal fluorescence intensity at all time intervals. CONCLUSION: Overall, the results confirmed the potential of Epl-loaded MNLCs as a direct approach for Epl ocular delivery.


Assuntos
Nanoestruturas , Animais , Galinhas , Córnea , Portadores de Fármacos , Eplerenona , Feminino , Lipídeos , Tamanho da Partícula , Coelhos
20.
J Clin Hypertens (Greenwich) ; 23(9): 1706-1714, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34432358

RESUMO

Numerous studies have demonstrated that sympathetic nervous system overactivation during exercise in hypertensive rodents and humans is due, in part, to an exaggerated reflex response known as the exercise pressor reflex. Our prior studies have implicated a key role of mineralocorticoid receptor activation in mediating an augmented exercise pressor reflex in spontaneously hypertensive rats, which is mitigated by blockade with eplerenone. However, the effect of eplerenone on exercise pressor reflex has not been assessed in human hypertension. Accordingly, the authors performed a randomized crossover study to compare the effects of eplerenone to another antihypertensive drug from a different class amlodipine on sympathetic nerve activity (SNA) in 14 patients with uncomplicated hypertension. The authors found that amlodipine unexpectedly augmented the increase in SNA during the second minute of isometric handgrip, which persisted into the post-exercise circulatory arrest period (∆ SNA, from rest of 15 ± 2 vs. 9 ± 2 vs. 10 ± 2 bursts/min, amlodipine vs. baseline vs. eplerenone, respectively, p < .01), suggesting an exaggerated muscle metaboreflex function. Eplerenone did not alter sympathetic responses to exercise or post-exercise circulatory arrest in the same hypertensive individuals. In conclusions, our studies provide the first direct evidence for a potentially unfavorable potentiation of muscle metaboreflex by amlodipine during isometric handgrip exercise in hypertensive patients whereas eplerenone has no significant effect. Our study may have clinical implications in terms of selection of antihypertensive agents that have the least detrimental effects on sympathetic neural responses to isometric exercise.


Assuntos
Hipertensão , Anlodipino/farmacologia , Animais , Pressão Sanguínea , Estudos Cross-Over , Eplerenona , Força da Mão , Humanos , Hipertensão/tratamento farmacológico , Músculo Esquelético , Ratos
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