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1.
Zhonghua Zhong Liu Za Zhi ; 42(6): 486-490, 2020 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-32575945

RESUMO

Objective: To investigate the effects of targeted artery perfusion of verapamil and chemotherapy drugs on advanced non-small cell lung cancer (NSCLC). Methods: Sixty patients with advanced NSCLC who were admitted to the Central Hospital of Zhumadian from April 2016 to April 2018 were selected as the research subjects. They were divided into the observation group (26 cases) and the control group (34 cases) according to the treatment method. Patients in the observation group were treated with targeted artery perfusion of verapamil and chemotherapy drugs while the control group were treated with target artery perfusion of chemotherapy drugs alone.Both groups were treated continuously for more than 2 months. The short-term curative effect, adverse reactions, changes in immune function, levels of serum tumor markers and Karnofsky Performance Scale (KPS) scores before and after treatment as well as the prognosis were compared between the two groups. Results: The response rate and control rate in the observation group were 80.8% and 96.2%, higher than 55.9% and 76.5% in the control group (P<0.05). After treatment, CD4(+) levels and CD4(+) /CD8(+) in the observation group were (25.43±2.76)% and (0.88±0.11), lower than (27.56±2.79)% and (0.95±0.13) in the control group (P<0.05). After treatment, serum levels of CEA and CA50 in the observation group were (11.57±2.32)ng/ml and (16.62±3.28)U/ml, also lower than (15.87±2.66)ng/ml and (20.31±3.42)U/ml in the control group (P<0.05). There was no significant difference in adverse reactions between the two groups (P>0.05). After treatment, KPS score of the observation group was (81.44±2.76) points, higher than (79.62±2.38) points of the control group (P<0.05). The median survival time and progression-free median survival time of the observation group were 16.0 months and 7.5 months, respectively, significantly better than 10.0 months and 5.0 months of the control group (P<0.05). Conclusions: The treatment with target arterial perfusion of verapamil and chemotherapy drugs for advanced NSCLC can effectively improve the short-term curative effect, reduce serum levels of tumor markers, improve life quality and prolong the survival time. However, it has a certain inhibitory effect on the patient's immune function.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bloqueadores dos Canais de Cálcio/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Verapamil/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Infusões Intra-Arteriais , Avaliação de Estado de Karnofsky , Neoplasias Pulmonares/patologia , Resultado do Tratamento , Verapamil/administração & dosagem , Verapamil/efeitos adversos
2.
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
3.
Turk Kardiyol Dern Ars ; 48(4): 410-424, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32519978

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Infecções por Coronavirus/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/terapia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiarrítmicos/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/toxicidade , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/toxicidade , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/toxicidade , Interações Medicamentosas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Pandemias , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores da Agregação de Plaquetas/toxicidade , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Vasodilatadores/toxicidade
4.
Kardiologiia ; 60(3): 21-29, 2020 Mar 18.
Artigo em Russo | MEDLINE | ID: mdl-32375612

RESUMO

Objective To analyze a profile of hypotensive drug therapy in patients with arterial hypertension (АH) aged 55-84 in a sample of urban population at a current period of time (2015-2017).Materials and Methods AH is a leader among risk factors of cardiovascular diseases (CVD) due to its high prevalence and serious prognosis. Despite the availability of effective hypotensive drugs and guidelines on AH treatment, 50% of patients do not achieve blood pressure (BP) goals. Knowledge about drug correction of AH in the Russian population is limited to clinical studies. Taking into account changing approaches in management of patients with AH, the population-based evaluation of hypotensive treatment if relevant. A random population sample of males and females aged 55-84 (n=3.898) was evaluated in Novosibirsk in 2015-2017 (international project, Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE)). AH was diagnosed in presence of systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg and/or treatment with hypotensive drugs within the recent two weeks. Regular intake of medication for 12 months was evaluated with coding according to the Anatomic Therapeutic Chemical Classification System (АТХ / АТС).Results In the population sample aged 55-84, AH prevalence was 80.9 %, and 21.1 % of persons with AH did not receive drug therapy. Hypotensive medicines included (total/as a part of combination therapy) angiotensin-converting enzyme (ACE) inhibitors (42.3 % / 25.3 %), angiotensin II receptor blockers (ARBs) (30.3 % / 18.9 %), diuretics (22.6 % / 20.4 %), calcium channel blockers (20.2 % / 16.1 %), and beta-blockers (34.7 % / 27.6 %). 45.7 % of people with AH received a combination therapy. Effective BP control was achieved in 23.4 % of AH patients and in 29.6 % of patients receiving a hypotensive therapy. In the group of ineffective BP control, the proportion of females was lower, AH duration was longer, and blood glucose was higher than in the group of effective control.Conclusion In the sample of urban population aged 55-84 in 2015-2017, each fourth participant with AH and each third participant using hypotensive drugs achieved effective BP control. The therapy profile in AH patients included recommended drug classes. However, combination therapy was used insufficiently (50% of AH patients). By frequency of use, ACE inhibitors were on the first place, beta-blockers were on the second place, ARBs were on the third place, diuretics were on the fourth place, and calcium channel blockers were on the fifth place, which differed from the guidelines (the difference from the recommended priority ranking is that the drugs taking the first places in the guidelines were in fact on the 3rd and 4th places in their actual frequency of use). 20% of persons with AH did not receive hypotensive therapy, which significantly contributed to the insufficient BP control in the population.


Assuntos
Hipertensão , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos , Pressão Sanguínea , Bloqueadores dos Canais de Cálcio , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Federação Russa , População Urbana
5.
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
6.
Med Sci Monit ; 26: e923696, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32285846

RESUMO

BACKGROUND This study evaluated the impact of clinical features and concomitant conditions on the clinical selection of different renin-angiotensin system (RAS) inhibitors in patients with hypertension, and built a renin-angiotensin inhibitors selection model (RAISM) to provide a reference for clinical decision making. MATERIAL AND METHODS We included 213 hypertensive patients in the study cohort; patients were divided into two groups: the angiotensin-converting enzyme inhibitor (ACEI) combined with calcium channel blocker (CCB) group (ACEI+CCB group) and the angiotensin receptor antagonist (ARB) combined with CCB group (ARB+CCB group). Basic demographic characteristics and concomitant conditions of the patients were compared. Single-factor and multi-factor analysis was performed by adopting logistic regression model. The RAISM was established by utilizing the nomograph technology. C-index and calibration curve were used to evaluate the model's efficacy. RESULTS In the study, 34.27% of the patients used ACEI+CCB and 65.73% of patients used ARB+CCB. The difference in age, body mass index (BMI), elderly patient, diabetes, renal dysfunction, and hyperlipidemia between the 2 groups determined medication selection. To be specific, compared to the group using ARB+CCB, the odds ratios and 95% confidence interval (CI) of the aforementioned factors for the ACEI+CCB group were 0.476 (0.319-0.711), 1.274 (1.001-1.622), 0.365 (0.180-0.743), 0.471 (0.203-1.092), 0.542 (0.268-1.094), and 0.270 (0.100-0.728), respectively; The C-index of RAISM acquired from the model construction parameters was 0.699, and the correction curve demonstrated that the model has good discriminative ability. CONCLUSIONS The outcome of our study suggests that independent discriminating factors that influence the clinical selection of different RAS inhibitors were elderly patient, renal insufficiency, and hyperlipidemia; and the RAISM constructed in this study has good predictability and clinical benefit.


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/tratamento farmacológico , Adulto , Idoso , Tomada de Decisão Clínica , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Sistema Renina-Angiotensina
7.
Biochim Biophys Acta Rev Cancer ; 1873(2): 188364, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32275934

RESUMO

Hyperactivation of the Mitogen Activated Protein Kinase (MAPK) pathway is prevalent in melanoma, principally due to mutations in the BRAF and NRAS genes. MAPK inhibitors are effective only short-term, and recurrence occurs due to functional redundancies or intertwined pathways. The remodeling of Ca2+ signaling is also common in melanoma cells, partly through the increased expression of T-type channels (TTCCs). Here we summarize current knowledge about the prognostic value and molecular targeting of TTCCs. Furthermore, we discuss recent evidence pointing to TTCCs as molecular switches for melanoma chemoresistance, which set the grounds for novel combined therapies against the advanced disease.


Assuntos
Antineoplásicos/uso terapêutico , Canais de Cálcio Tipo T/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Linhagem Celular Tumoral , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , GTP Fosfo-Hidrolases/antagonistas & inibidores , GTP Fosfo-Hidrolases/genética , Humanos , Estimativa de Kaplan-Meier , Sistema de Sinalização das MAP Quinases/genética , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Mutação , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Resultado do Tratamento
9.
PLoS One ; 15(4): e0231711, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298357

RESUMO

Actively growing tumors are often histologically associated with Ki67 positivity, while the detection of invasiveness relies on non-quantitative pathologic evaluation of mostly advanced tumors. We recently reported that reduced expression of the Ca2+-dependent membrane-binding annexin A6 (AnxA6) is associated with increased expression of the Ca2+ activated RasGRF2 (GRF2), and that the expression status of these proteins inversely influence the growth and motility of triple negative breast cancer (TNBC) cells. Here, we establish that the reciprocal expression of AnxA6 and GRF2 is at least in part, dependent on inhibition of non-selective Ca2+ channels in AnxA6-low but not AnxA6-high TNBC cells. Immunohistochemical staining of breast cancer tissues revealed that compared to non-TNBC tumors, TNBC tumors express lower levels of AnxA6 and higher Ki67 expression. GRF2 expression levels strongly correlated with high Ki67 in pretreatment biopsies from patients with residual disease and with residual tumor size following chemotherapy. Elevated AnxA6 expression more reliably identified patients who responded to chemotherapy, while low AnxA6 levels were significantly associated with shorter distant relapse-free survival. Finally, the reciprocal expression of AnxA6 and GRF2 can delineate GRF2-low/AnxA6-high invasive from GRF2-high/AnxA6-low rapidly growing TNBCs. These data suggest that AnxA6 may be a reliable biomarker for distant relapse-free survival and response of TNBC patients to chemotherapy, and that the reciprocal expression of AnxA6 and GRF2 can reliably delineate TNBCs into rapidly growing and invasive subsets which may be more relevant for subset-specific therapeutic interventions.


Assuntos
Anexina A6/metabolismo , Canais de Cálcio/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Fatores ras de Troca de Nucleotídeo Guanina/metabolismo , Animais , Anexina A6/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Humanos , Antígeno Ki-67/metabolismo , Camundongos , Metástase Neoplásica/genética , Prognóstico , Transplante Heterólogo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Fatores ras de Troca de Nucleotídeo Guanina/genética
10.
PLoS One ; 15(4): e0231244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298274

RESUMO

BACKGROUND: Quantifying dose-dependent ultra-early edema and ultrastructural changes in the myocyte after drug delivery is important for the development of new mixed calcium channel blockers (CCBs). MATERIALS AND METHODS: Arterial cannulation was used to measure mean arterial pressure in real time; simultaneously, magnetic resonance imaging proton density mapping was used to quantify edema 5-55 min after the delivery of L-type CCBs, T- and L-type CCBs, and solvent to a spontaneously hypertensive rat model. Transmission electron microscopy was used to show ultrastructural changes in the myocyte. RESULTS: Analysis of variance showed significant differences among the three groups in mean arterial pressure reduction (F = 246.36, P = 5.75E-25), ultra-early level of edema (ULE) (F = 175.49, P = 5.62E-22), and dose-dependent level of edema (DLE) (F = 199.48, P = 4.28E-23). Compared with the solvent's mean arterial pressure reduction (2.65±6.56±1.64), ULE (1.16±0.09±0.02), and DLE (0.0010±0.0001±0.0000), post hoc tests showed that T- and L-type CCBs had better mean arterial pressure reduction (90.67±11.58±2.90, P = 1.06E-24 vs. 68.34±15.19±3.80, P = 1.76E-12), lower ULE (1.53±0.14±0.04, P = 4.74E-9 vs. 2.08±0.18±0.04, P = 2.68E-22), and lower DLE (0.0025±0.0004±0.0001, P = 1.14E-11 vs. 0.0047±0.0008±0.0002, P = 2.10E-11) than L- type CCBs. Transmission electron microscopy showed that T- and L-type CCBs caused fewer ultrastructural changes in the myocytes after drug delivery than L-type CCBs. CONCLUSION: T- and L-type CCBs produced less ultra-early and dose-dependent edema, fewer ultrastructural changes in the myocyte, and a greater antihypertensive effect. Proton density mapping combined with arterial cannulation and transmission electron microscopy allowed for quantification of ultra-early and dose-dependent edema, antihypertensive efficacy, and ultrastructural changes in the myocyte. This is important for the evaluation of induced vasodilatory edema.


Assuntos
Anti-Hipertensivos/farmacologia , Artérias/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Edema/diagnóstico , Hipertensão/tratamento farmacológico , Células Musculares/efeitos dos fármacos , Animais , Anti-Hipertensivos/administração & dosagem , Artérias/fisiopatologia , Bloqueadores dos Canais de Cálcio/administração & dosagem , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo T/metabolismo , Edema/induzido quimicamente , Ratos , Ratos Endogâmicos SHR
11.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(4): 520-525, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32344475

RESUMO

Objective: To understand the current status of anti-hypertensive drug use in patients with hypertension in the Southwest areas of China. Methods: Based on the Program of Screening and Intervention Subjects with High Risk Cardiovascular Diseases, this study presented information on adults aged 35-75 in Southwest China by convenient sampling method, from January 2016 to November 2018. Basic information and cardiovascular related data were collected. Data on hypertensive patients were recorded, including names, doses and frequency of anti-hypertensive drugs they used. Information on the use of anti-hypertensive drugs among different hypertension subgroups, potential related characteristics, types and combination patterns of drugs, etc., were analyzed. Results: A total of 394 957 subjects were included in the study, with 159 014 identified as being hypertensive [mean age (58.8±9.5) years, 40.2% male]. 29.8% of them ever received antihypertensive drugs. A total of 30 445 of the patients reported detailed information of the drugs they ever used and 22.5% of them received therapy of combined drugs. Rates of using combination therapy were consistent among subgroups with different age, gender, blood pressure level and history of cardiovascular and cerebrovascular diseases. Results from the multivariate logistic regression analysis showed that patients with previous cardiovascular and cerebrovascular events, obesity or diabetes were more likely to have received combined therapy, while patients with less education or lower income were in the opposite. Calcium antagonists (58.6%) were the main drugs being used in single drug therapy, while traditional fixed-dose combination drugs (31.4%) were the most common ones in the drug-combination therapy, followed by angiotensin converting enzyme inhibitor/angiotensin receptor blocker combined with calcium antagonists (22.4%). Angiotensin converting enzyme inhibitor/angiotensin receptor blocker combined with beta blocker was the main drug used in patients with coronary heart disease. Conclusions: Treatment programs using the antihypertensive drugs for hypertensive patients in Southwest China needs to be improved, since the irrational use of antihypertensive drugs still exists. However, we would encourage the use of combination therapy for hypertensive patients.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/tratamento farmacológico , Adulto , Idoso , Pressão Sanguínea , China/epidemiologia , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
N Engl J Med ; 382(17): 1608-1618, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32227756

RESUMO

BACKGROUND: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS: At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS: Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).


Assuntos
Angiografia Coronária , Ponte de Artéria Coronária , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/cirurgia , Intervenção Coronária Percutânea , Insuficiência Renal Crônica/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Bloqueadores dos Canais de Cálcio/uso terapêutico , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Fatores de Risco
13.
PLoS One ; 15(3): e0230655, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32208439

RESUMO

BACKGROUND: T-wave area dispersion (TW-Ad) is a novel electrocardiographic (ECG) repolarization marker associated with sudden cardiac death. However, limited data is available on the clinical correlates of TW-Ad. In addition, there are no previous studies on cardiovascular drug effects on TW-Ad. In this study, we examined the relation between TW-Ad and left ventricular mass. We also studied the effects of four commonly used antihypertensive drugs on TW-Ad. METHODS: A total of 242 moderately hypertensive males (age, 51±6 years; office systolic/diastolic blood pressure during placebo, 153±14/100±8 mmHg), participating in the GENRES study, were included. Left ventricular mass index was determined by transthoracic echocardiography. Antihypertensive four-week monotherapies (a diuretic, a beta-blocker, a calcium channel blocker, and an angiotensin receptor antagonist) were administered in a randomized rotational fashion. Four-week placebo periods preceded all monotherapies. The average value of measurements (over 1700 ECGs in total) from all available placebo periods served as a reference to which measurements during each drug period were compared. RESULTS: Lower, i.e. risk-associated TW-Ad values correlated with a higher left ventricular mass index (r = -0.14, p = 0.03). Bisoprolol, a beta-blocker, elicited a positive change in TW-Ad (p = 1.9×10-5), but the three other drugs had no significant effect on TW-Ad. CONCLUSIONS: Our results show that TW-Ad is correlated with left ventricular mass and can be modified favorably by the use of bisoprolol, although demonstration of any effects on clinical endpoints requires long-term prospective studies. Altogether, our results suggest that TW-Ad is an ECG repolarization measure of left ventricular arrhythmogenic substrate.


Assuntos
Anti-Hipertensivos/uso terapêutico , Ventrículos do Coração/fisiopatologia , Hipertensão/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Bisoprolol/farmacologia , Bisoprolol/uso terapêutico , Pressão Sanguínea , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Morte Súbita Cardíaca/prevenção & controle , Diuréticos/farmacologia , Diuréticos/uso terapêutico , Método Duplo-Cego , Ecocardiografia , Ventrículos do Coração/anatomia & histologia , Ventrículos do Coração/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Função Ventricular/efeitos dos fármacos
14.
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
15.
Am J Cardiol ; 125(9): 1429-1435, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32156412

RESUMO

Combination therapies are often needed to modify the concomitant risk factors for cardiovascular disease. Nonadherence to cardiovascular medications is a relevant concern, especially in polytherapy. We conducted a population-based, cohort study with the aim of quantifying the level of adherence and its related determinants in patients exposed to free 3-drug combination therapies, namely concurrent use of angiotensin-converting-enzyme inhibitor (ACEi), calcium channel blocker (CCB), and statin or of ACEi, statin, and low-dose aspirin. Within Health Search Database, we selected a cohort of adult patients concurrently prescribed with ACEi, CCB, and statin, as well as those prescribed with ACEi, statin and low-dose aspirin, from the January 1, 2002 to the December 31, 2014. Adherent patients were concurrent users of triple free pill regimen with a proportion of days covered ≥80% during 1-year follow-up; demographics and clinical determinants of 1-year adherence were identified by multivariate logistic regression. We found that more than half of patients prescribed with triple free drug combination therapy with ACEi plus CCB plus statin or ACEi plus statin plus low-dose aspirin, were found to be nonadherent to these treatments. Males and patients at high/very-high cardiovascular risk were more likely to be adherent, whereas depression and atrial fibrillation were associated with nonadherence. Our findings indicate that sex, cardiovascular risk, presence of atrial fibrillation, and depression can influence adherence to polytherapy. In conclusion, given that patients suffering from multiple cardiovascular risk factors are at higher risk of fatal events, strategies are needed to improve medication adherence to combination therapies.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Aspirina/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Prim Dent J ; 8(4): 34-39, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32127092

RESUMO

INTRODUCTION:
Drug-influenced gingival enlargement (DIGE) is a reaction to specific medications, namely phenytoin, ciclosporin and calcium channel blockers. DIGE is encountered increasingly in clinical practice due to the widespread use of calcium channel blocker drugs particularly. Approaches to its management are discussed in this review.
Methods: Narrative review of the literature and discussion of clinical implications.
Findings: Management of DIGE involves nonsurgical treatment and may require surgical reduction of the overgrown gingival tissues. Management is complicated by the difficulties in achieving adequate plaque control, given the unfavourable contour of the enlarged gingival tissues, and the high frequency of recurrence of DIGE after surgical management. Replacing the drug involved can be very beneficial in selected cases, but the management of the underlying medical condition limits its application. The decision to replace a drug is not the responsibility of the dental practitioner, but the patient's physician may make it after consultation.
Conclusions: Management of DIGE can be challenging and may require close co-operation between the dental practitioner and a hygienist, a periodontist and the patient's physician. Long term supportive maintenance programmes need to be in place for optimal outcomes.


Assuntos
Placa Dentária , Hiperplasia Gengival , Bloqueadores dos Canais de Cálcio , Humanos
17.
Dtsch Med Wochenschr ; 145(3): 161-165, 2020 02.
Artigo em Alemão | MEDLINE | ID: mdl-32018289

RESUMO

While monitoring and symptomatic care is sufficient for most intoxicated patients, some develop life threatening symptoms. We present recent changes in the recommendations of the treatment in patients with calcium channel blocker, beta blocker and high dose paracetamol intoxications. Additionally, new insights in the efficacy and safety of the use of physostigmine in anticholinergic patients and beta blockers in cocaine intoxication are discussed as well as the specific considerations in the resuscitation of intoxicated patients.


Assuntos
Cuidados Críticos , Envenenamento/tratamento farmacológico , Acetaminofen/envenenamento , Antagonistas Adrenérgicos beta/envenenamento , Bloqueadores dos Canais de Cálcio/envenenamento , Carbono/uso terapêutico , Humanos , Fisostigmina/efeitos adversos , Fisostigmina/uso terapêutico
18.
BMC Complement Med Ther ; 20(1): 14, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-32020867

RESUMO

BACKGROUND: Euphorbia hirta (Linn) family Euphorbiaceae has been used in indigenous system of medicine for the treatment of gastrointestinal disorders. This study was designed to determine the pharmacological basis for the medicinal use of E. hirta in diarrhea and constipation. METHODS: The aqueous-methanol extract of whole herb of E. hirta (EH.Cr) and its petroleum ether (Pet.EH), chloroform (CHCl3.EH), ethyl acetate (Et.Ac.EH) and aqueous (Aq.EH) fractions were tested in the in-vivo experiments using Balb/c mice, while the in-vitro studies were performed on isolated jejunum and ileum preparations of locally bred rabbit and Sprague Dawley rats, respectively, using PowerLab data system. RESULTS: Qualitative phytochemical analysis showed the presence of alkaloids, saponins, flavonoids, tannins, phenols, cardiac glycosides, while HPLC of EH.Cr showed quercetin in high proportion. In mice, EH.Cr at the dose of 500 and 1000 mg/kg showed 41 and 70% protection from castor oil-induced diarrhea, respectively, similar to the effect of quercetin and loperamide, while at lower doses (50 and 100 mg/kg), it caused an increase in the fecal output. In loperamide-induced constipated mice, EH.Cr also displayed laxative effect with respective values of 28.6 and 35.3% at 50 and 100 mg/kg. In rabbit jejunum, EH.Cr showed atropine-sensitive inhibitory effect in a concentration-dependent manner, while quercetin and nifedipine exhibited atropine-insensitive effects. Fractions of E. hirta also produced atropine-sensitive inhibitory effects except Pet.EH and CHCl3.EH. On high (80 mM) and low (20 mM) K+ - induced contractions, the crude extract and fractions exhibited a concentration-dependent non-specific inhibition of both spasmogens and displaced concentration-response curves of Ca++ to the right with suppression of the maximum effect similar to the effect quercetin and nifedipine. Fractions showed wide distribution of spasmolytic and Ca++ antagonist like effects. In rat ileum, EH.Cr and its fractions exhibited atropine-sensitive gut stimulant effects except Pet.EH. CONCLUSION: The crude extract of E. hirta possesses antidiarrheal effect possibly mediated through Ca++ antagonist like gut inhibitory constituents, while its laxative effect was mediated primarily through muscarinic receptor agonist like gut stimulant constituents. Thus, these findings provide an evidence to the folkloric use of E. hirta in diarrhea and constipation.


Assuntos
Cálcio/metabolismo , Constipação Intestinal/tratamento farmacológico , Diarreia/tratamento farmacológico , Euphorbia/química , Extratos Vegetais/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Cromatografia Líquida , Modelos Animais de Doenças , Feminino , Íleo/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Paquistão , Coelhos , Ratos , Ratos Sprague-Dawley
19.
Internist (Berl) ; 61(3): 270-276, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-32030435

RESUMO

BACKGROUND: The treatment of polyneuropathy includes symptomatic therapy of sensory, motor and autonomic dysfunctions. AIM: This article provides an overview of the current treatment recommendations for polyneuropathy, focusing on pain. METHODS: Current treatment guidelines will be discussed based on a literature research. RESULTS: Calcium-channel anticonvulsants gabapentin/pregabalin as well as antidepressants duloxetine and amitriptyline are recommended as first line therapeutics. Alternatively, topical therapeutics can be used in the case of localized disorders. In individual cases, opioids or other antidepressants/anticonvulsants may be effective. Pharmacological treatment is often limited due to adverse events, which affect the central nervous system in particular. DISCUSSION: In general, treatment for polyneuropathy should follow a multimodal concept and include the treatment of other symptoms. When choosing pain medication, comorbidities, patient's age and adverse events need to be taken into consideration. Phenotype-based stratification may support specialized pain therapy and achieve the best medical treatment.


Assuntos
Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Neuralgia/tratamento farmacológico , Polineuropatias/tratamento farmacológico , Amitriptilina/uso terapêutico , Analgésicos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Pregabalina/uso terapêutico
20.
Mol Pharmacol ; 97(4): 250-258, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32015008

RESUMO

Phenytoin is a hydantoin derivative that is used clinically for the treatment of epilepsy and has been reported to have antiarrhythmic actions on the heart. In a failing heart, the elevated diastolic Ca2+ leak from the sarcoplasmic reticulum can be normalized by the cardiac ryanodine receptor 2 (RyR2) inhibitor, dantrolene, without inhibiting Ca2+ release during systole or affecting Ca2+ release in normal healthy hearts. Unfortunately, dantrolene is hepatotoxic and unsuitable for chronic long-term administration. Because phenytoin and dantrolene belong to the hydantoin class of compounds, we test the hypothesis that dantrolene and phenytoin have similar inhibitory effects on RyR2 using a single-channel recording of RyR2 activity in artificial lipid bilayers. Phenytoin produced a reversible inhibition of RyR2 channels from sheep and human failing hearts. It followed a hyperbolic dose response with maximal inhibition of ∼50%, Hill coefficient ∼1, and IC50 ranging from 10 to 20 µM. It caused inhibition at diastolic cytoplasmic [Ca2+] but not at Ca2+ levels in the dyadic cleft during systole. Notably, phenytoin inhibits RyR2 from failing human heart but not from healthy heart, indicating that phenytoin may selectively target defective RyR2 channels in humans. We conclude that phenytoin could effectively inhibit RyR2-mediated release of Ca2+ in a manner paralleling that of dantrolene. Moreover, the IC50 of phenytoin in RyR2 is at least threefold lower than for other ion channels and clinically used serum levels, pointing to phenytoin as a more human-safe alternative to dantrolene for therapies against heart failure and cardiac arrythmias. SIGNIFICANCE STATEMENT: We show that phenytoin, a Na channel blocker used clinically for treatment of epilepsy, is a diastolic inhibitor of cardiac calcium release channels [cardiac ryanodine receptor 2 (RyR2)] at doses threefold lower than its current therapeutic levels. Phenytoin inhibits RyR2 from failing human heart and not from healthy heart, indicating that phenytoin may selectively target defective RyR2 channels in humans and pointing to phenytoin as a more human-safe alternative to dantrolene for therapies against heart failure and cardiac arrhythmias.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cardiotônicos/farmacologia , Insuficiência Cardíaca/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Fenitoína/farmacologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/patologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cardiotônicos/uso terapêutico , Dantroleno/farmacologia , Dantroleno/uso terapêutico , Relação Dose-Resposta a Droga , Vesículas Extracelulares , Insuficiência Cardíaca/patologia , Humanos , Bicamadas Lipídicas , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fenitoína/uso terapêutico , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo , Ovinos
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