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1.
BMC Infect Dis ; 21(1): 262, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722197

RESUMO

INTRODUCTION: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. METHODS: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. RESULTS: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality. CONCLUSION: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Sistema Renina-Angiotensina , Reino Unido , Adulto Jovem
2.
Hypertension ; 77(3): 833-842, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33423528

RESUMO

After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations. We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs). Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020. We excluded patients with a history of diabetes, known cardiovascular disease, chronic renal failure, or chronic respiratory disease during the previous 5 years, to only consider patients treated for uncomplicated hypertension and to limit indication bias. The primary end point was time to hospitalization for COVID-19. The secondary end point was time to intubation/death during a hospital stay for COVID-19. In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19. ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65-0.83] and 0.84 [0.76-0.93], respectively) and a lower risk of intubation/death. Risks were slightly lower for ACE inhibitor users than for ARB users. This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs. These results, if confirmed, tend to contradict previous hypotheses and raise new hypotheses.


Assuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Pandemias , Receptores Virais/efeitos dos fármacos , /fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Comorbidade , Suscetibilidade a Doenças , Uso de Medicamentos , Feminino , Seguimentos , França/epidemiologia , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/epidemiologia , Intubação Intratraqueal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
3.
Cochrane Database Syst Rev ; 10: CD011064, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000470

RESUMO

BACKGROUND: Calcium channel blockers (CCBs) are used to manage hypertension which is highly prevalent among people with chronic kidney disease (CKD). The treatment for hypertension is particularly challenging in people undergoing dialysis. OBJECTIVES: To assess the benefits and harms of calcium channel blockers in patients with chronic kidney disease requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies to 27 April 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs that compared any type of CCB with other CCB, different doses of the same CCB, other antihypertensives, control or placebo were included. The minimum study duration was 12 weeks. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random-effects model and results expressed as risk ratio (RR), risk difference (RD) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: This review included 13 studies (24 reports) randomising 1459 participants treated with long-term haemodialysis. Nine studies were included in the meta-analysis (622 participants). No studies were performed in children or in those undergoing peritoneal dialysis. Overall, risk of bias was assessed as unclear to high across most domains. Random sequence generation and allocation concealment were at low risk of bias in eight and one studies, respectively. Two studies reported low risk methods for blinding of participants and investigators, and outcome assessment was blinded in 10 studies. Three studies were at low risk of attrition bias, eight studies were at low risk of selective reporting bias, and five studies were at low risk of other potential sources of bias. Overall, the certainty of the evidence was low to very low for all outcomes. No events were reported for cardiovascular death in any of the comparisons. Other side effects were rarely reported and studies were not designed to measure costs. Five studies (451 randomised adults) compared dihydropyridine CCBs to placebo or no treatment. Dihydropyridine CCBs may decrease predialysis systolic (1 study, 39 participants: MD -27.00 mmHg, 95% CI -43.33 to -10.67; low certainty evidence) and diastolic blood pressure level (2 studies, 76 participants; MD -13.56 mmHg, 95% CI -19.65 to -7.48; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Dihydropyridine CCBs may make little or no difference to occurrence of intradialytic hypotension (2 studies, 287 participants; RR 0.54, 95% CI 0.25 to 1.15; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Other side effects were not reported. Eight studies (1037 randomised adults) compared dihydropyridine CCBs to other antihypertensives. Dihydropyridine CCBs may make little or no difference to predialysis systolic (4 studies, 180 participants: MD 2.44 mmHg, 95% CI -3.74 to 8.62; I2 = 0%, low certainty evidence) and diastolic blood pressure (4 studies, 180 participants: MD 1.49 mmHg, 95% CI -2.23 to 5.21; I2 = 0%, low certainty evidence) compared to other antihypertensives. There was no evidence of a difference in the occurrence of intradialytic hypotension (1 study, 92 participants: RR 2.88, 95% CI 0.12 to 68.79; very low certainty evidence) between dihydropyridine CCBs to other antihypertensives. Other side effects were not reported. Dihydropyridine CCB may make little or no difference to predialysis systolic (1 study, 40 participants: MD -4 mmHg, 95% CI -11.99 to 3.99; low certainty evidence) and diastolic blood pressure (1 study, 40 participants: MD -3.00 mmHg, 95% CI -7.06 to 1.06; low certainty evidence) compared to non-dihydropyridine CCB. There was no evidence of a difference in other side effects (1 study, 40 participants: RR 0.13, 95% CI 0.01 to 2.36; very low certainty evidence) between dihydropyridine CCB and non-dihydropyridine CCB. Intradialytic hypotension was not reported. AUTHORS' CONCLUSIONS: The benefits of CCBs over other antihypertensives on predialysis blood pressure levels and intradialytic hypotension among people with CKD who required haemodialysis were uncertain. Effects of CCBs on other side effects and cardiovascular death also remain uncertain. Dihydropyridine CCBs may decrease predialysis systolic and diastolic blood pressure level compared to placebo or no treatment. No studies were identified in children or peritoneal dialysis. Available studies have not been designed to measure the effects on costs. The shortcomings of the studies were that they recruited very few participants, had few events, had very short follow-up periods, some outcomes were not reported, and the reporting of outcomes such as changes in blood pressure was not done uniformly across studies. Well-designed RCTs, conducted in both adults and children with CKD requiring both haemodialysis and peritoneal dialysis, evaluating both dihydropyridine and non-dihydropyridine CCBs against other antihypertensives are required. Future research should be focused on outcomes relevant to patients (including death and cardiovascular disease), blood pressure changes, risk of side effects and healthcare costs to assist decision-making in clinical practice.


Assuntos
Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hipertensão/tratamento farmacológico , Diálise Renal , Insuficiência Renal Crônica/terapia , Adulto , Viés , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Di-Hidropiridinas/efeitos adversos , Humanos , Hipotensão/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações
4.
High Blood Press Cardiovasc Prev ; 27(6): 527-537, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33001356

RESUMO

INTRODUCTION: Benidipine and amlodipine are two well-known drugs used in hypertensive patients with chronic kidney disease (CKD). AIM: In this systematic review we aimed to compare benidipine and amlodipine in terms of efficacy in the management of hypertensive patients. METHODS: We searched PubMed, Cochrane CENTRAL, SCOPUS and Web of Science for relevant clinical trials and excluded observational studies. Quality appraisal was evaluated according to GRADE and we assessed the risk of bias using the Cochrane's risk of bias tool. We included the following outcomes: Systolic blood pressure, diastolic blood pressure, heart rate, estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio. Data were pooled as mean differences (MD) with relative 95% confidence intervals (CI). RESULTS: Eight studies were eligible for our meta-analysis. We found no significant difference between both drugs regarding systolic (MD = - 0.21 [- 1.48, 1.89], (P = 0.81) and diastolic (MD = 0.01[- 0.51, 0.53], (P = 0.97)) blood pressure measurements. The overall heart rate did not differ as well (MD = - 0.03 [- 1.63, 1.57], (P = 0.97)). We found that benidipine was statistically better than amlodipine in terms of eGFR (MD = 1.07 [0.43, 1.71], (P = 0.001)), and urinary albumin/creatinine ratio (MD = - 43.41 [- 53.53, - 33.29], (P < 0.00001)). CONCLUSIONS: Finally we conclude that benidipine seems to show more positive and promising results in the management of hypertensive patients with chronic kidney disease.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hipertensão/tratamento farmacológico , Vasodilatadores/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anlodipino/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Di-Hidropiridinas/efeitos adversos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Resultado do Tratamento , Vasodilatadores/efeitos adversos
5.
Pharmacol Res Perspect ; 8(5): e00653, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32930523

RESUMO

More than ten million patients worldwide have been diagnosed with coronavirus disease 19 (COVID-19) to date (WHO situation report, 1st July 2020). There is no vaccine to prevent infection with the causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), nor a cure. In the struggle to devise potentially useful therapeutics in record time, the repurposing of existing compounds is a key route of action. In this hypothesis paper, we argue that the bisbenzylisoquinoline and calcium channel blocker tetrandrine, originally extracted from the plant Stephania tetrandra and utilized in traditional Chinese medicine, may have potential in the treatment of COVID-19 and should be further investigated. We collate and review evidence for tetrandrine's putative mechanism of action in viral infection, specifically its recently discovered antagonism of the two-pore channel 2 (TPC2). While tetrandrine's particular history of use provides a very limited pharmacological dataset, there is a suggestion from the available evidence that it could be effective at doses used in clinical practice. We suggest that further research to investigate this possibility should be conducted.


Assuntos
Antivirais/administração & dosagem , Benzilisoquinolinas/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Canais de Cálcio/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Animais , Antivirais/efeitos adversos , Benzilisoquinolinas/efeitos adversos , Betacoronavirus/patogenicidade , Bloqueadores dos Canais de Cálcio/efeitos adversos , Canais de Cálcio/metabolismo , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Interações Medicamentosas , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Transdução de Sinais
6.
Pediatr Cardiol ; 41(7): 1301-1318, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32915293

RESUMO

Alterations in blood pressure are common during the perioperative period in infants and children. Perioperative hypertension may be the result of renal failure, volume overload, or activation of the sympathetic nervous system. Concerns regarding end-organ effects or postoperative bleeding may mandate regulation of blood pressure. During the perioperative period, various pharmacologic agents have been used for blood pressure control including sodium nitroprusside, nitroglycerin, ß-adrenergic antagonists, fenoldopam, and calcium channel antagonists. The following manuscript outlines the commonly used pharmacologic agents for perioperative BP including dosing regimens and adverse effect profiles. Previously published clinical trials are discussed and efficacy in the perioperative period reviewed.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Adolescente , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Criança , Pré-Escolar , Fenoldopam/efeitos adversos , Fenoldopam/farmacologia , Fenoldopam/uso terapêutico , Humanos , Hipertensão/etiologia , Lactente , Masculino , Nitroprussiato/efeitos adversos , Nitroprussiato/farmacologia , Nitroprussiato/uso terapêutico , Período Perioperatório , Insuficiência Renal/complicações , Resultado do Tratamento
7.
High Blood Press Cardiovasc Prev ; 27(5): 379-388, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32705504

RESUMO

INTRODUCTION: Structural and functional properties of the left ventricle (LV) wall have been reported to be altered in hypertension, even at early stages of the disease. Abnormal adipokine levels affect blood pressure regulation. Hypo-adiponectinaemia and hyper-leptinaemia were reported in hypertension. AIM: To evaluate the effects of valsartan versus amlodipine on LV deformation also, on plasma adiponectin and leptin levels in hypertensive individuals. METHODS: LV strain was measured by two-dimensional speckle tracking echocardiography, plasma levels of adiponectin and leptin was determined in 30 healthy individuals served as control group and in 200 hypertensive patients before and after treatment for 6 months with either valsartan 160 mg or amlodipine 10 mg. RESULTS: Compared to control group longitudinal strain was significantly affected in hypertensive patients, adiponectin was significantly lower while TNF-α, hs-CRP and leptin levels were significantly higher in hypertensive group. A significant improvement in LV functions, along with a decrease in leptin and increase in adiponectin levels in valsartan group compared to amlodipine group. CONCLUSIONS: Our results indicate that valsartan is superior to amlodipine when it comes to affecting the hormonal function of human adipose tissue. Valsartan has a beneficial effect on LV deformation and function presented in GLS.


Assuntos
Adipocinas/sangue , Anlodipino/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ecocardiografia , Hipertensão/terapia , Valsartana/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Adiponectina/sangue , Adulto , Anlodipino/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Bloqueadores dos Canais de Cálcio/efeitos adversos , Egito , Feminino , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Valsartana/efeitos adversos
9.
J Korean Med Sci ; 35(25): e232, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32597045

RESUMO

BACKGROUND: There is a controversy whether it is safe to continue renin-angiotensin system blockers in patients with coronavirus disease 2019 (COVID-19). We analyzed big data to investigate whether angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers have any significant effect on the risk of COVID-19. Population-based cohort study was conducted based on the prescription data from nationwide health insurance records. METHODS: We investigated the 1,374,381 residents aged ≥ 40 years living in Daegu, the epicenter of the COVID-19 outbreak, between February and March 2020. Prescriptions of antihypertensive medication during the year before the outbreak were extracted from the National Health Insurance Service registry. Medications were categorized by types and stratified by the medication possession ratios (MPRs) of antihypertensive medications after controlling for the potential confounders. The risk of COVID-19 was estimated using a difference in difference analysis. RESULTS: Females, older individuals, low-income earners, and recently hospitalized patients had a higher risk of infection. Patients with higher MPRs of antihypertensive medications had a consistently lower risk of COVID-19 than those with lower MPRs of antihypertensive medications and non-users. Among patients who showed complete compliance, there was a significantly lower risk of COVID-19 for those prescribed angiotensin II receptor blockers (relative risk [RR], 0.751; 95% confidence interval [CI], 0.587-0.960) or calcium channel blockers (RR, 0.768; 95% CI, 0.601-0.980). CONCLUSION: Renin-angiotensin system blockers or other antihypertensive medications do not increase the risk of COVID-19. Patients should not stop antihypertensive medications, including renin-angiotensin system blockers, because of concerns of COVID-19.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , República da Coreia/epidemiologia
10.
N Engl J Med ; 382(25): 2441-2448, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32356628

RESUMO

BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Inibidores de Simportadores de Cloreto de Sódio/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Teorema de Bayes , Betacoronavirus , Bloqueadores dos Canais de Cálcio/efeitos adversos , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , New York , Pandemias , Pontuação de Propensão , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos
11.
Am J Physiol Cell Physiol ; 318(5): C913-C930, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32159364

RESUMO

Whole exome sequencing (WES) was used in the research of familial pulmonary arterial hypertension (FPAH). CAV1 and KCNK3 were found as two novel candidate genes of FPAH. However, few pathogenic genes were identified in idiopathic pulmonary arterial hypertension (IPAH). We conducted WES in 20 unrelated IPAH patients who did not carry the known PAH-pathogenic variants among BMPR2, CAV1, KCNK3, SMAD9, ALK1, and ENG. We found a total of 4,950 variants in 3,534 genes, including 4,444 single-nucleotide polymorphisms and 506 insertions/deletions (InDels). Through the comprehensive and multilevel analysis, we disclosed several novel signaling cascades significantly connected to IPAH, including variants related to cadherin signaling pathway, dilated cardiomyopathy, glucose metabolism, immune response, mucin-type O-glycosylation, phospholipase C (PLC)-activating G protein-coupled receptor (GPCR) signaling pathway, vascular contraction and generation, and voltage-dependent Ca2+ channels. We also conducted validation studies in five mutant genes related to PLC-activating GPCR signaling pathway potentially involved in intracellular calcium regulation through Sanger sequencing for mutation accuracy, qRT-PCR for mRNA stability, immunofluorescence for subcellular localization, Western blotting for protein level, Fura-2 imaging for intracellular calcium, and proliferation analysis for cell function. The validation experiments showed that those variants in CCR5 and C3AR1 significantly increased the rise of intracellular calcium and the variant in CCR5 profoundly enhanced proliferative capacity of human pulmonary artery smooth muscle cells. Thus, our study suggests that multiple genetically affected signaling pathways take effect together to cause the formation of IPAH and the development of right heart failure and may further provide new therapy targets or putative clues for the present treatments such as limited therapeutic effectiveness of Ca2+ channel blockers.


Assuntos
Hipertensão Pulmonar Primária Familiar/genética , Insuficiência Cardíaca/genética , Receptores CCR5/genética , Receptores de Complemento/genética , Adulto , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Sinalização do Cálcio/genética , Caveolina 1/genética , Proliferação de Células/efeitos dos fármacos , Hipertensão Pulmonar Primária Familiar/tratamento farmacológico , Hipertensão Pulmonar Primária Familiar/patologia , Feminino , Células HEK293 , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Proteínas do Tecido Nervoso/genética , Canais de Potássio de Domínios Poros em Tandem/genética , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Transdução de Sinais/genética , Sequenciamento Completo do Exoma
12.
Sci Rep ; 10(1): 2011, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029849

RESUMO

The development of proteinuria restricts the dose of anti-angiogenic agents, thereby reducing their efficacy. Thus, this retrospective study was undertaken to identify predictive factors of the development of angiogenesis inhibitor-induced proteinuria, and to elucidate if there is a difference in the likelihood of proteinuria among anti-angiogenic agents or cancer types, to help guide future strategies to improve the safety, efficacy, and quality of life of patients receiving chemotherapy. Between April 2014 and February 2019, 124 cancer patients at our outpatient chemotherapy center who were receiving chemotherapy with bevacizumab, ramucirumab, or aflibercept were enrolled. Variables related to the development of proteinuria were extracted from the patients' clinical records and used for regression analysis. The level of the proteinuria was evaluated based on CTCAE version 5. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the development of proteinuria. The Wilcoxon/Kruskal-Wallis test was used to identify significant differences between groups. Significant factors identified included systolic blood pressure (SBP) [odds ratio (OR) = 1.031, 95% confidence interval (CI) = 1.005-1.058; P = 0.0197], number of cycles (OR = 1.049, 95% CI = 1.018-1.082; P = 0.0019), and calcium channel blocker use (OR = 2.589, 95% CI = 1.090-6.146; P = 0.0311). There was no difference among the three anti-angiogenic agents (P = 0.4969) or among cancer types (P = 0.2726) in the likelihood of proteinuria. In conclusion, SBP, number of cycles, and calcium channel blocker use were identified as significant predictors of the development of angiogenesis inhibitor-induced proteinuria. There was no difference among the three anti-angiogenic agents or among cancer types.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias/tratamento farmacológico , Proteinúria/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Pressão Sanguínea/fisiologia , Bloqueadores dos Canais de Cálcio/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria/induzido quimicamente , Proteinúria/fisiopatologia , Qualidade de Vida , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
13.
Am J Cardiol ; 125(6): 907-915, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31959429

RESUMO

Clinical studies have shown that calcium channel blockers (CCB) can mitigate the progression of atherosclerosis. Their role in the primary prevention of peripheral artery disease (PAD) is unclear. We conducted a meta-analysis of randomized control trials (RCT) to compare the impact of CCB on the incidence of PAD in patients with hypertension. A comprehensive review of the literature was performed in PubMed and Cochrane registry. Studies were included if they were RCT and had outcome data on PAD with a follow-up duration of at least 6 months. CCB formed the intervention group, whereas the control group was constituted by either placebo or active treatment with any of the other antihypertensive medications. A random-effects meta-analysis was performed, and we report odds ratio as a measure of treatment effect. Our search identified 934 trials, of which 7 RCTs with 71,971 patients fulfilled the inclusion criteria. The mean duration of follow-up was 3.8 years. In patients receiving CCB, PAD events occurred in 547 out of 27,502 patients (2%) compared with 1,263 out of 42,659 patients in the control group (3%). Based on the random-effect model, the odds for development of PAD in hypertensive patients treated with CCB compared with the control group was 0.70 (95% confidence interval of 0.58 to 0.86, p = 0.0005). In conclusion, this meta-analysis of RCTs of hypertensive patients, we found that treatment with CCB was strongly associated with a decrease in the PAD compared with other antihypertensive agents or placebo.


Assuntos
Aterosclerose/prevenção & controle , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/tratamento farmacológico , Doença Arterial Periférica/prevenção & controle , Bloqueadores dos Canais de Cálcio/efeitos adversos , Seguimentos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Doc Ophthalmol ; 140(3): 279-287, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31900741

RESUMO

PURPOSE: Pregabalin binds to the α2-δ1/α2-δ2 subunits of the voltage-gated L-type calcium channel (LTCC), which is expressed in rod/cone photoreceptor terminals. The purpose of this report was to describe electroretinographic abnormalities associated with pregabalin treatment. CASE PRESENTATION: This is an observational case report. A 49-year-old female reported photophobia and night blindness in her left eye after 10 months of pregabalin administration. One month after the symptoms, ophthalmic examinations were performed, which revealed good visual acuity and no remarkable fundus findings. However, full-field electroretinography (ERG) of the left eye revealed a decreased b-wave in rod ERG, a slightly decreased a-wave and severely decreased b-wave (negative ERG) in bright flash ERG, decreased a- and b-waves in cone ERG, and decreased b-waves in 30-Hz flicker ERG. These findings are similar to those seen in incomplete congenital stationary night blindness, whereas the right eye ERG showed normal responses, except for a square a-wave in cone ERG. The ERG gradually improved from 1 to 12 months after discontinuing pregabalin. Finally, b-waves in bright flash ERG and cone ERG responses largely recovered, but b-waves in rod ERG and a-waves in bright flash ERG only partially recovered in the left eye. The square a-wave recovered to normal in the right eye. CONCLUSIONS: This is the first report to indicate that ERG abnormalities might be associated with pregabalin treatment. Our results suggest that pregabalin may affect LTCC function via the α2-δ1/α2-δ2 subunits, which leads to defective synaptic transmission from rod/cone photoreceptors to bipolar cells.


Assuntos
Bloqueadores dos Canais de Cálcio/efeitos adversos , Eletrorretinografia/efeitos dos fármacos , Cegueira Noturna/induzido quimicamente , Fotofobia/induzido quimicamente , Pregabalina/efeitos adversos , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Canais de Cálcio Tipo L , Adaptação à Escuridão , Feminino , Humanos , Pessoa de Meia-Idade , Cegueira Noturna/fisiopatologia , Fotofobia/fisiopatologia , Acuidade Visual/fisiologia
15.
Drugs Aging ; 37(2): 77-81, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31797247

RESUMO

Prescribing cascades are where a drug adverse reaction is wrongly attributed to the emergence of a new condition, which leads to further drug prescribing. This promotes polypharmacy, adverse drug reactions and therapeutic burden. An example of a prescribing cascade is the co-prescribing of loop diuretics to treat the peripheral oedema caused by calcium channel blocker (CCB) drugs. Although well recognised, this is still a combination of medications taken by millions of people worldwide. CCBs have no prognostic benefit in heart failure and have an absolute risk increase for oedema of around 8-18% (number needed to harm 6-13). In the treatment of hypertension, they also increase the risk of oedema and a new diagnosis of heart failure without having any major advantages over alternative drugs. The best way to manage the oedema caused by CCBs is to switch to an alternative medication. Only where this is not possible or fails to achieve therapeutic goals would the CCB-loop diuretic combination appear to be justified. In many cases, therapeutic practice could be improved by targeting people on CCB-loop diuretic combinations for medication review. This could improve quality of life and reduce polypharmacy, adverse drug reactions, therapeutic burden and financial costs for millions of people worldwide.


Assuntos
Anti-Hipertensivos/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Prescrição Inadequada/prevenção & controle , Padrões de Prática Médica/normas , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Edema/prevenção & controle , Humanos , Hipertensão/tratamento farmacológico , Prescrição Inadequada/estatística & dados numéricos , Qualidade de Vida , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico
16.
Drug Res (Stuttg) ; 70(2-03): 91-96, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31746448

RESUMO

Nifedipine is one of calcium channel blockers that commonly used clinically to treat hypertension and angina in Egyptian patients. A sustained-release (SR) formulation of nifedipine is available in the Egyptian community and administered twice daily. This study aimed to to compare the pharmacokinetics and safety profiles of a 20 mg SR and IR (immediate release) formulation of nifedipine after single-dose administration in healthy Egyptian subjects. Randomized, crossed open-label two- way clinical trial, in 16 healthy adult volunteers, of 24.75±5.20 years, with BMI 23.26±1.756 were assessed. Blood samples were collected at predefined times for 48 h and analyzed for Nifedipine plasma concentrations using validated reversed phase liquid chromatography method with ultraviolet detection. Pharmacokinetics was determined using non- compartmental model pharmacokinetics and analyzed using one-way ANOVA (P≤0.05). Following a single oral administration, SR formulation had a lower Cmax, compared to IR formulation (54.46±17.75 , 107.45±29.85 ng/mL, respectively), and Tmax was significantly longer (2.97 vs. 1.13 h) for the SR and IR formulation, respectively. There was no significant difference between the SR and the IR formulations for AUC0-last and AUC0-∞ (326.7±98.28 vs. 309.27±105.53 ng·h·mL-1 and 380.9 ± 105.24 vs. 334.36±108.1 ng·h·mL-1, respectively). SR formulation of nifedipine showed similar pharmacokinetics to the IR Formulation (F%=1.049), but it additionally allows a less frequent administration. Therefore, The nifedipine SR and IR formulations were well tolerated and displayed comparable safety profiles.


Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Nifedipino/administração & dosagem , Administração Oral , Adolescente , Adulto , Área Sob a Curva , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/farmacocinética , Estudos Cross-Over , Preparações de Ação Retardada , Egito , Jejum , Humanos , Masculino , Nifedipino/efeitos adversos , Nifedipino/farmacocinética , Comprimidos , Adulto Jovem
17.
Expert Opin Investig Drugs ; 29(1): 1-4, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31825681

RESUMO

Introduction: Paroxysmal supraventricular tachycardia (SVT) can be very bothersome and may potentially lead to considerable health-care utilization. Non-parenteral medication is currently unavailable for the rapid termination of paroxysmal SVT. However, an intranasal spray formulation of etripamil, a short-acting calcium-channel blocker, is under investigation as a convenient, safe, and rapidly efficacious means to terminate paroxysmal SVT.Areas covered: This review summarizes the clinical rationale, potential benefit, and clinical trials safety and efficacy data for the use of etripamil nasal spray to terminate paroxysmal SVT.Expert opinion: Based on the efficacy and tolerability demonstrated in phase 1 and 2 clinical trials, etripamil nasal spray is a potential convenient, safe, and effective means for patients to terminate paroxysmal SVT. It has the potential to improve quality of life, reduce health-care burden, and alter the current management paradigm for many patients with SVT. Further ongoing evaluation in ambulatory patients will help to determine its real-life practicality, safety, and effectiveness.


Assuntos
Benzoatos/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Sprays Nasais , Taquicardia Paroxística/tratamento farmacológico , Taquicardia Supraventricular/tratamento farmacológico , Benzoatos/efeitos adversos , Benzoatos/farmacologia , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/farmacologia , Humanos , Qualidade de Vida , Taquicardia Paroxística/fisiopatologia , Taquicardia Supraventricular/fisiopatologia , Fatores de Tempo
18.
Hip Int ; 30(1): 101-106, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30821177

RESUMO

PURPOSE: To evaluate the predictive value of pre-fracture medication usage on 30-day mortality following a hip fracture. METHODS: Information on age, sex, fracture type, time of death and Charlson co-morbidity index (CCI) was collected from the Danish National Patient Registry on all patients above 60 years, sustaining a hip fracture during the period January 1995 to December 2013. Information on drug usage was obtained from the Danish National Prescription Database. Hazard ratios were calculated with 30-day mortality as the outcome. A univariate and 3 multivariate analyses were conducted with increasing adjustments, starting with age, sex and fracture type, adding co-morbidity and dose in the latter. RESULTS: 141,201 patients were included and a total of 12 drugs/drug groups were identified for analysis. Increased mortality was evident in all analyses for antiarrhythmics, beta blockers, proton pump inhibitors, loop diuretics, opioids, acetaminophen and for psycholeptics. For ACE-inhibitors, increased mortality was found in all analyses, except after adjustment for co-morbidity and dose. For thiazide diuretics, a significantly reduced mortality was evident in all but the univariate analyses while NSAIDs and statins were associated with a significantly reduced mortality in all analyses. For calcium channel blockers, an insignificant decrease was found after adjustment for dose. Further analysis showed a dose-response relationship for all drugs except ACE-inhibitors and calcium channel blockers. CONCLUSION: The study shows a correlation between pre-fracture usage of certain drugs and 30 day mortality after a hip fracture.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Fraturas do Quadril/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Dinamarca/epidemiologia , Feminino , Fraturas do Quadril/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências
19.
J Stomatol Oral Maxillofac Surg ; 121(3): 308-311, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31055091

RESUMO

Gingival enlargements (GEs) can be caused by local, systemic diseases or drugs. Three molecules can be responsible of GEs: ciclosporin, phenytoin and calcium channel blockers (CCBs). We report the case of a 56-year-old male treated by Amlodipine, a CCB, for hypertension for many years and who recently developed a severe GE affecting both mandibular and maxillary arches inducing dental malposition. The histological examination showed non-specific inflammation with a predominance of lymphocytes. Amlodipine was suspected and suspended in agreement with his physician. One month later, the enlargement significantly reduced but GE was so severe and dental malposition so marked that all the teeth but the canines were extracted. No recurrence was noted one year later. This exceptional case should encourage every practitioner to be vigilant with patient treated with CCBs and their potential side effects and consequences.


Assuntos
Anlodipino/efeitos adversos , Crescimento Excessivo da Gengiva/induzido quimicamente , Crescimento Excessivo da Gengiva/diagnóstico , Crescimento Excessivo da Gengiva/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade
20.
JAMA Netw Open ; 2(12): e1918425, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31880802

RESUMO

Importance: Calcium channel blockers, specifically dihydropyridine calcium channel blockers (DH CCBs, eg, amlodipine), may cause lower-extremity edema. Anecdotal reports suggest this may result in a prescribing cascade, where DH CCB-induced edema is treated with loop diuretics. Objective: To assess the magnitude and characteristics of the DH CCB prescribing cascade. Design, Setting, and Participants: This cohort study used a prescription sequence symmetry analysis to assess loop diuretic initiation before and after the initiation of DH CCBs among patients aged 20 years or older without heart failure. Data from a private insurance claims database from 2005 to 2017 was analyzed. Use of loop diuretics associated with initiation of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and other commonly used medications was used as negative controls. Data were analyzed from March 2019 through October 2019. Exposures: Initiation of DH CCB or negative control medications. Main Outcomes and Measures: The temporality of loop diuretic initiation relative to DH CCB or negative control initiation. Secular trend-adjusted sequence ratios (aSRs) with 95% CIs were calculated using data from 360 days before and after initiation of DH CCBs. Results: Among 1 206 093 DH CCB initiators, 55 818 patients (4.6%) (33 100 [59.3%] aged <65 years; 32 916 [59.0%] women) had a new loop diuretic prescription 360 days before or after DH CCB initiation, resulting in an aSR of 1.87 (95% CI, 1.84-1.90). An estimated 1.44% of DH CCB initiators experienced the prescribing cascade. The aSR was disproportionately higher among DH CCB initiators who were prescribed high doses (aSR, 2.20; 95% CI, 2.13-2.27), initiated amlodipine (aSR, 1.89; 95% CI, 1.86-1.93), were men (aSR, 1.96; 95% CI, 1.91-2.01), and used fewer antihypertensive classes (aSR, 2.55; 95% CI, 2.47-2.64). The evaluation of ACE inhibitors or ARBs as negative controls suggested hypertension progression may have tempered the incidence of the prescribing cascade (aSR for ACE inhibitors and ARBs, 1.27; 95% CI, 1.24-1.29). Conclusions and Relevance: This study found an excessive use of loop diuretics following initiation of DH CCBs that cannot be completely explained by secular trends or hypertension progression. The prescribing cascade was more pronounced among those initially prescribed a high dose of DH CCBs.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Di-Hidropiridinas/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Adulto , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/tratamento farmacológico , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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