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2.
Curr Cardiol Rep ; 22(3): 12, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31997014

RESUMO

PURPOSE OF REVIEW: To examine the current clinical evidence behind the use of calcium channel blockers (CCB) and beta-blockers (BB) for the treatment of patients with stable coronary artery disease (SCAD) and their effect on mortality. RECENT FINDINGS: Current evidence suggests that BB use as a first line antianginal medication is associated with lower 5-year all-cause mortality only in patients who had MI within a year. This could be driven due to their effects reducing the sympathetic neuro-hormonal activation of more acutely ill patients. The use of CCB as an antianginal therapy, although proven effective in multiple trials both as monotherapy and combined with other agents, has not shown mortality benefit. Both BB and CCB are effective antianginals, and the selection among them depends on the patient clinical presentation and comorbidities. BB are the only ones that have shown survival benefit in SCAD, particularly the first year post-MI.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Humanos , Infarto do Miocárdio
3.
Handb Exp Pharmacol ; 260: 161-186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31820179

RESUMO

A large series of different ion channels have been identified and investigated as potential targets for new medicines for the treatment of a variety of human diseases, including pain. Among these channels, the voltage gated calcium channels (VGCC) are inhibited by drugs for the treatment of migraine, neuropathic pain or intractable pain. Transient receptor potential (TRP) channels are emerging as important pain transducers as they sense low pH media or oxidative stress and other mediators and are abundantly found at sites of inflammation or tissue injury. Low pH may also activate acid sensing ion channels (ASIC) and mechanical forces stimulate the PIEZO channels. While potent agonists of TRP channels due to their desensitizing action on pain transmission are used as topical applications, the potential of TRP antagonists as pain therapeutics remains an exciting field of investigation. The study of ASIC or PIEZO channels in pain signaling is in an early stage, whereas antagonism of the purinergic P2X3 channels has been reported to provide beneficial effects in chronic intractable cough. The present chapter covers these intriguing channels in great detail, highlighting their diverse mechanisms and broad potential for therapeutic utility.


Assuntos
Bloqueadores do Canal Iônico Sensível a Ácido/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Neuralgia/tratamento farmacológico , Manejo da Dor , Canais de Receptores Transientes de Potencial/antagonistas & inibidores , Canais Iônicos Sensíveis a Ácido , Canais de Cálcio , Humanos , Inflamação
4.
Urologiia ; (5): 48-52, 2019 Dec.
Artigo em Russo | MEDLINE | ID: mdl-31808632

RESUMO

OBJECTIVE: to evaluate the nephroprotective effect of lercanidipine, its effect on the dynamics of creatinine clearance and blood cytokine levels in patients with nephrolithiasis with obstructive uropathy during renal drainage. MATERIAL AND METHODS: 66 patients were included in the study with concretions of the pelvic segment and the presence of obstruction according to instrumental methods of examination. In order to prevent the occurrence of infectious complications before lithotripsy patients the first stage was performed installation of nephrostomic drainage, followed by antibacterial, anti-inflammatory therapy. Patients were divided into 2 groups: the first (33 patients) received standard therapy, the second (33 people) additionally received lercanidipine at a dose of 10 mg per day for 1 month. Determined the concentration of IL-8, VEGF, MCP-1, G-CSF and GM-CSF in the blood serum by the method of solid-phase ELISA. The glomerular filtration rate was calculated using the CKD-EPI formula. All studies were performed at the preoperative stage, on 7, 14, 21 and 28 days after renal drainage. RESULTS: In the appointment of lercanidipine, there was a more rapid decrease in levels of IL-8, VEGF, MS-1, GM-CSF in serum (21 days), and an improvement in renal function, compared with the group that did not receive nephroprotective therapy. CONCLUSION: The administration of lercanidipine may contribute to a more rapid recovery of renal function and normalization of blood cytokine levels. This drug can be used in the complex treatment of patients with nephrolithiasis with obstructive uropathy.


Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Citocinas/sangue , Di-Hidropiridinas/uso terapêutico , Rim/efeitos dos fármacos , Nefrolitíase/cirurgia , Fármacos Neuroprotetores/uso terapêutico , Urolitíase/cirurgia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Bloqueadores dos Canais de Cálcio/administração & dosagem , Di-Hidropiridinas/administração & dosagem , Taxa de Filtração Glomerular , Humanos , Fármacos Neuroprotetores/administração & dosagem , Resultado do Tratamento
5.
Lancet ; 394(10211): 1816-1826, 2019 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-31668726

RESUMO

BACKGROUND: Uncertainty remains about the optimal monotherapy for hypertension, with current guidelines recommending any primary agent among the first-line drug classes thiazide or thiazide-like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers, in the absence of comorbid indications. Randomised trials have not further refined this choice. METHODS: We developed a comprehensive framework for real-world evidence that enables comparative effectiveness and safety evaluation across many drugs and outcomes from observational data encompassing millions of patients, while minimising inherent bias. Using this framework, we did a systematic, large-scale study under a new-user cohort design to estimate the relative risks of three primary (acute myocardial infarction, hospitalisation for heart failure, and stroke) and six secondary effectiveness and 46 safety outcomes comparing all first-line classes across a global network of six administrative claims and three electronic health record databases. The framework addressed residual confounding, publication bias, and p-hacking using large-scale propensity adjustment, a large set of control outcomes, and full disclosure of hypotheses tested. FINDINGS: Using 4·9 million patients, we generated 22 000 calibrated, propensity-score-adjusted hazard ratios (HRs) comparing all classes and outcomes across databases. Most estimates revealed no effectiveness differences between classes; however, thiazide or thiazide-like diuretics showed better primary effectiveness than angiotensin-converting enzyme inhibitors: acute myocardial infarction (HR 0·84, 95% CI 0·75-0·95), hospitalisation for heart failure (0·83, 0·74-0·95), and stroke (0·83, 0·74-0·95) risk while on initial treatment. Safety profiles also favoured thiazide or thiazide-like diuretics over angiotensin-converting enzyme inhibitors. The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes. INTERPRETATION: This comprehensive framework introduces a new way of doing observational health-care science at scale. The approach supports equivalence between drug classes for initiating monotherapy for hypertension-in keeping with current guidelines, with the exception of thiazide or thiazide-like diuretics superiority to angiotensin-converting enzyme inhibitors and the inferiority of non-dihydropyridine calcium channel blockers. FUNDING: US National Science Foundation, US National Institutes of Health, Janssen Research & Development, IQVIA, South Korean Ministry of Health & Welfare, Australian National Health and Medical Research Council.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Criança , Estudos de Coortes , Pesquisa Comparativa da Efetividade/métodos , Bases de Dados Factuais , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Medicina Baseada em Evidências/métodos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Adulto Jovem
7.
Rev Cardiovasc Med ; 20(3): 139-151, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601088

RESUMO

Effective therapy of hypertension represents a key strategy for reducing the burden of cardiovascular disease and its associated mortality. The significance of voltage dependent L-type Ca²âº channels to Ca²âº influx, and of their regulatory mechanisms in the development of heart disease, is well established. A wide variety of L-type Ca²âº channel inhibitors and Ca²âº antagonists have been found to be beneficial not only in the treatment of hypertension, but also in myocardial infarction and heart failure. Over the past two decades, another class of Ca²âº channel - the voltage independent store-operated Ca²âº channel - has been implicated in the regulation and fine tuning of Ca²âº entry in both cardiac and smooth muscle cells. Store-operated Ca²âº channels are activated by the depletion of Ca²âº stores within the endoplasmic/sarcoplasmic reticulum, or by low levels of cytosolic Ca²âº, thereby facilitating agonist-induced Ca²âº influx. Store-operated Ca²âº entry through this pivotal pathway involves both stromal interaction molecule (STIM) and Orai channels. Different degrees of changes in these proteins are considered to promote Ca²âº entry and hence contribute to the pathogenesis of cardiovascular dysfunction. Several blockers of store-operated Ca²âº channels acting at the level of both STIM and Orai channels have been shown to depress Ca²âº influx and lower blood pressure. However, their specificity, safety, and clinical significance remain to be established. Thus, there is an ongoing challenge in the development of selective inhibitors of store-operated Ca²âº channels that act in vascular smooth muscles for the improved treatment of hypertension.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio Ativados pela Liberação de Cálcio/antagonistas & inibidores , Hipertensão/tratamento farmacológico , Músculo Liso Vascular/efeitos dos fármacos , Moléculas de Interação Estromal/antagonistas & inibidores , Vasodilatadores/uso terapêutico , Animais , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Ativados pela Liberação de Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Moléculas de Interação Estromal/metabolismo , Resultado do Tratamento , Vasodilatadores/efeitos adversos
8.
Undersea Hyperb Med ; 46(4): 483-494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509904

RESUMO

The aim of this study was to establish the effect of combined therapy with hyperbaric oxygen (HBO2) therapy and verapamil, amlodipine or nicorandil on functional recovery and oxidative stress markers after ischemia in the isolated rat heart. The study included 48 rats (Wistar albino, male gender, eight weeks old, body weight 200±50g). All animals were exposed to HBO2 treatment over 14 days. Isolated heart rats were perfused by the Langendorff retrograde method at a constant coronary pressure of 70 cm H2O. After stabilization period the hearts were divided into the following groups: HBO2 group (animals exposed to only HBO2 preconditioning); HBO2 + verapamil; HBO2 + amlodipine; andHBO2 + nicorandil (animals pretreated with HBO2 and appropriate pharmacological agent). Afterward, the hearts in all groups were subjected to 20-minute global ischemia and 30-minute reperfusion. Parameters of heart function were registered, including maximum and minimum rate of pressure development, systolic and diastolic left ventricular pressure, heart rate and coronary flow. Levels of pro-oxidants such as index of lipid peroxidation, measured as thiobarbituric acid-reactive substances, nitrites, levels of superoxide anion radicals and hydrogen peroxide were determined in coronary venous effluent. Changes in cardiac tissue were evaluated by hematoxylin and eosin staining. Obtained results clearly indicate that blockage of calcium channel or the activation of adenosine triphosphate-sensitive potassium (KATP) in combination with HBO2 prevented ischemia/reperfusion-induced cardiac deleterious effects, thus contributing to improvement of functional recovery of the heart. However, future studies are certainly necessary for better understanding the mechanisms through which combination of these two maneuvers of preconditioning triggers cardioprotection.


Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Oxigenação Hiperbárica , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/terapia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Bloqueadores dos Canais de Potássio/uso terapêutico , Anlodipino/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Terapia Combinada/métodos , Circulação Coronária , Coração , Frequência Cardíaca/efeitos dos fármacos , Precondicionamento Isquêmico Miocárdico/efeitos adversos , Peroxidação de Lipídeos , Masculino , Miocárdio/patologia , Nicorandil/uso terapêutico , Estresse Oxidativo , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Verapamil/uso terapêutico
9.
Int J Clin Pharmacol Ther ; 57(10): 483-488, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31426904

RESUMO

AIM: The aim of this study was to investigate the potential association between antihypertensive therapy and the incidence of Parkinson's disease (PD) in patients followed in general practices in Germany. MATERIALS AND METHODS: This study included patients aged ≥ 40 who had received initial diagnoses of PD in 1,203 general practices in Germany between January 2013 and December 2017 (index date). After applying similar inclusion criteria, PD cases were matched to non-PD controls using propensity scores based on age, sex, and treating physician. The primary outcome of the study was the incidence of PD as a function of the use of antihypertensive drugs (diuretics, ß-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers). Logistic regression models were conducted to study the association between the use of antihypertensive drugs and the incidence of PD after adjusting for codiagnoses and antihypertensive cotherapy. RESULTS: The present study included 9,127 patients with PD and 9,127 patients without PD (mean age: 75.8 years; 48.4% women). The at-least-once use of diuretics (44.8% versus 38.4%; odds ratio (OR) = 1.23 (1.15-1.32)) was associated with an increased incidence of PD. However, this effect was not maintained for a therapy duration of at least 3 years, and no association was observed between the diuretic therapy duration and PD incidence. For all other antihypertensive drug classes, we found no significant associations with PD incidence. CONCLUSION: No association was found between antihypertensive therapy duration and PD incidence. Further epidemiological studies are needed to compare the effects of subclasses of antihypertensives on PD.


Assuntos
Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Doença de Parkinson/complicações , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Feminino , Medicina Geral , Alemanha , Humanos , Hipertensão/complicações , Incidência , Masculino
10.
J Physiol Pharmacol ; 70(2)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31443094

RESUMO

Urocortin 2 (Ucn2) - corticotropin-releasing hormone receptor 2 signalling has favourable effects in the cardiovascular system, including vasodilation, lowering of blood pressure and systemic peripheral resistance, increase in cardiac output and cardiac contractility, as well as cardioprotection against ischemia-reperfusion injury. Vasodilation and lowering of blood pressure seem to be very interesting and important effects, but their mechanism and interaction with the antihypertensive drugs have not been evaluated. The aim of the present study was to assess the relationship between Ucn2 concentration and antihypertensive therapy in patients with primary hypertension. We examined a group of 65 patients with primary hypertension receiving at least 3 antihypertensive drugs. In all of them plasma level of Ucn2, anthropometric measurements, biochemical tests, ambulatory blood pressure monitoring (ABPM), and echocardiography were performed. There were no differences in Ucn2 level related to beta-blockers, calcium channel blockers or diuretics, but we observed that in patients treated with angiotensin converting enzyme inhibitors (ACEI) (n = 52) serum Ucn2 levels were significantly higher than in patients treated with angiotensin-receptor blockers (ARBs) (n = 13) (10.93 versus 5.56 ng/mL; P < 0.05). Moreover, we did not observe any differences in terms of blood pressure on ABPM, biochemical measurements, left ventricular mass index, or presence of diabetes. In addition, in a small subgroup receiving alpha-blockers we also found a lower level of Ucn2, with coexisting higher systolic blood pressure at night, higher left ventricle mass index (LVMI) and more frequent occurrences of diabetes compared to non-alpha-blockers. Our findings suggest that the hypotensive action of renin-angiotensin-aldosterone system blockade may be related to the urocortin system. Ucn2 may be an important element in the mosaic of blood pressure-lowering factors in patients treated for essential hypertension.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hormônio Liberador da Corticotropina/metabolismo , Hipertensão/tratamento farmacológico , Urocortinas/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial/métodos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Feminino , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Humanos , Hipertensão/metabolismo , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos
11.
High Blood Press Cardiovasc Prev ; 26(5): 399-404, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463886

RESUMO

INTRODUCTION: Polytherapy is often required to treat the comorbidity of hypertension and hyperlipidemia. Fixed-dose co-formulation, rather than free combinations, simplifies medication taking and also improves adherence to medication, which is the key for a successful management of these conditions. AIM: To determine the number of patients potentially eligible for treatment with triple fixed-dose atorvastatin/perindopril/amlodipine (CTAPA), and to estimate if an unmet medical need exists among CTAPA free combination treated patients. METHODS: This observational retrospective study was based on administrative databases of 3 Italian Local Health Units. The cohort comprised adult patients with at least one prescription of amlodipine and perindopril (either as free combination or co-formulated) and atorvastatin during 2014. Follow-up period started on the date of prescription of the 3 molecules (index date) and lasted 1 year. Adherence to CTAPA was analyzed during follow-up, by using the proportion of days covered (PDC). RESULTS: 2292 patients (9.1 per 10,000 beneficiaries) had a prescription for CTAPA as free combination. Only 1249 (54.5%) were adherent to the therapy (PDC ≥ 80%); among them, a small percentage required dosage modification. The number of patients with CTAPA increased during the study period. Discontinuation of drugs prescribed the year before interested 582 patients in 2014, and 522 in 2015. Considering the Italian national population (n = 60,782,668), it was estimated that 69,542 hypertensive patients could be eligible for fixed-dose CTAPA during 2014. CONCLUSIONS: Real-world analysis among patients with free combination therapy can be applied to estimate the eligible population for fixed combination, and to evaluate the appropriateness of their prescriptions. Moreover, fixed-dose CTAPA could effectively improve adherence, which was calculated to be low in the free combination cohort.


Assuntos
Anlodipino/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Atorvastatina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/tratamento farmacológico , Perindopril/uso terapêutico , Idoso , Biomarcadores/sangue , Bases de Dados Factuais , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Itália , Lipídeos/sangue , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
Hypertension ; 74(3): 614-622, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31327267

RESUMO

Selection of antihypertensive treatment according to self-defined ethnicity is recommended by some guidelines but might be better guided by individual genotype rather than ethnicity or race. We compared the extent to which variation in blood pressure response across different ethnicities may be explained by genetic factors: genetically defined ancestry and gene variants at loci known to be associated with blood pressure. We analyzed data from 5 trials in which genotyping had been performed (n=4696) and in which treatment responses to ß-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blocker, thiazide or thiazide-like diuretic and calcium channel blocker were available. Genetically defined ancestry for proportion of African ancestry was computed using the 1000 genomes population database as a reference. Differences in response to the thiazide diuretic hydrochlorothiazide, the ß-blockers atenolol and metoprolol, the angiotensin-converting enzyme inhibitor lisinopril, and the angiotensin receptor blocker candesartan were more closely associated to genetically defined ancestry than self-defined ethnicity in admixed subjects. A relatively small number of gene variants related to loci associated with drug-signaling pathways (KCNK3, SULT1C3, AMH, PDE3A, PLCE1, PRKAG2) with large effect size (-3.5 to +3.5 mm Hg difference in response per allele) and differing allele frequencies in black versus white individuals explained a large proportion of the difference in response to candesartan and hydrochlorothiazide between these groups. These findings suggest that a genomic precision medicine approach can be used to individualize antihypertensive treatment within and across populations without recourse to surrogates of genetic structure such as self-defined ethnicity.


Assuntos
Afro-Americanos/genética , Anti-Hipertensivos/uso terapêutico , Grupo com Ancestrais do Continente Europeu/genética , Loci Gênicos/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Variação Genética/efeitos dos fármacos , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/etnologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Estados Unidos
13.
Int J Mol Sci ; 20(14)2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31331039

RESUMO

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however, new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (CaVs). Calcium entering through CaVs is crucial for multiple neuronal processes. In this review, we will summarize recent findings that link CaVs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of CaVs structure, classification, function, expression and pharmacology. Next, we will summarize tools to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in CaV genes when available. Finally, we will review pharmacological evidence of the use of CaV modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of CaVs.


Assuntos
Canais de Cálcio/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Transtornos Mentais/genética , Animais , Biomarcadores , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio/química , Canais de Cálcio/metabolismo , Ensaios Clínicos como Assunto , Regulação da Expressão Gênica , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Transtornos Mentais/diagnóstico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/metabolismo , Terapia de Alvo Molecular , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Relação Estrutura-Atividade , Resultado do Tratamento
14.
BMC Pharmacol Toxicol ; 20(1): 44, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349878

RESUMO

BACKGROUND: This analysis was designed to investigate the relationship between drug application and mortality rate in Chinese older coronary artery disease (CAD)/chronic heart failure (CHF) patients with and without low glomerular filtration rate (GFR). METHODS: All 1050 Chinese hospitalized patients with diagnosed CAD were included in this analysis, and Cox Regression was used to analyze the relationship between drug application and mortality rate after multivariate adjustment. Low GFR was defined as GFR < 60 ml/min/1.73m2. RESULTS: There were 372 patients (35.4%) with low GFR in patients with CAD (1050 patients), and 168 patients (51.4%) in patients with CHF (327 patients). In CAD patients without low GFR, clopidogrel [P = 0.028, odds ratio (OR): 0.620, 95% confidence interval (CI): 0.404-0.951] rather than aspirin (P = 0.173) was significantly associated with lower mortality rate. Statins (P < 0.001, OR: 0.287, 95% CI: 0.180-0.456) were significantly associated with lower mortality rate. In CAD patients with low GFR, aspirin, clopidogrel and statins had no significant relationship with mortality rate (P > 0.05 for all). In CHF patients without low GFR, statins were significantly associated with lower mortality rate (P < 0.001, OR: 0.220, 95% CI: 0.098-0.490). In CHF patients with low GFR, statins had no significant relationship with mortality rate (P > 0.05 for all). CONCLUSION: Clopidogrel but not aspirin was beneficial in Chinese older CAD patients without low GFR rather than those with low GFR, and statins benefited for Chinese older CAD/CHF patients without low GFR rather than those with low GFR. These discoveries might offer some help for the therapy of Chinese older patients with cardiovascular/renal diseases.


Assuntos
Doença da Artéria Coronariana , Taxa de Filtração Glomerular , Insuficiência Cardíaca , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Aspirina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Digoxina/uso terapêutico , Uso de Medicamentos , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nitratos/uso terapêutico
15.
Presse Med ; 48(11 Pt 1): 1222-1228, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31303372

RESUMO

Erectile dysfunction (ED) is not routinely discussed with patients in cardiology practices whereas it may impact the ability of patients to stay on therapy. Most of the studies about ED and antihypertensive therapies have several methodological limitations. Diuretics and beta-blockers have been shown to have a deleterious effect on ED. ISRA inhibitors, calcium antagonists, vasodilator beta-blockers and alpha-blockers have been shown to have a neutral impact on ED. Angiotensin 2 inhibitors, nebivolol and alpha-blockers use has sometimes beneficial effect on ED. In case of ED due to antihypertensive treatment, drugs can be switched each other but careful attention in patients with a high cardiovascular risk is required.


Assuntos
Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Disfunções Sexuais Fisiológicas/induzido quimicamente , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Bloqueadores do Receptor Tipo 2 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , 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 , Doenças Cardiovasculares/tratamento farmacológico , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Substituição de Medicamentos , Humanos , Masculino , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Fatores de Risco , Disfunções Sexuais Fisiológicas/prevenção & controle
16.
Medicina (Kaunas) ; 55(7)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269687

RESUMO

Background and objectives: The etiology of anemia associated with heart failure is not fully understood, but there are data suggesting the involvement of multiple mechanisms, including various drug therapies used in patients with heart failure. Our primary objective was to evaluate the impact of beta blockers, angiotensin-converting enzyme inhibitors, and calcium-channel blockers on iron metabolism in patients with heart failure. Materials and Methods: This was a prospective observational study that included patients diagnosed with heart failure and iron deficiency (defined by ferritin <100 µg/L, or 100-300 µg/L with transferrin saturation <20%). Patients with anemia secondary to a known cause were excluded. Results: We found a statistically significant correlation between beta-blocker treatment and ferritin values (p = 0.02). Iron, hemoglobin, and hematocrit levels were significantly lower in the patients using calcium-channel blockers than those who were not. We also found a statistically significant indirect correlation (p = 0.04) between the use of angiotensin-converting enzyme inhibitors and hematocrit levels. Conclusion: The contribution of our study arises from the additional data regarding the drug-induced etiology of iron deficiency. Practitioners should be aware of the potential impact of therapeutic recommendations and this should imply a close monitoring of the biochemical parameters of iron deficiency in this category of patients.


Assuntos
Anemia/etiologia , Insuficiência Cardíaca/tratamento farmacológico , Distúrbios do Metabolismo do Ferro/etiologia , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Anemia/sangue , Anemia/complicações , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Feminino , Insuficiência Cardíaca/sangue , Humanos , Ferro/análise , Ferro/sangue , Distúrbios do Metabolismo do Ferro/sangue , Masculino , Pessoa de Meia-Idade
17.
BMC Cancer ; 19(1): 615, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234828

RESUMO

BACKGROUND: A higher density of tumor-infiltrating lymphocytes (TILs) can lead to greater therapeutic effects and improved prognoses in cancer treatment. Similar results have been observed in breast cancer, particularly in triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2-enriched breast cancer. Calcium channel blockers (CCBs) are antihypertensive drugs (AHTs) that have also been reported to suppress the functions of T cells and macrophages. In this study, we evaluated TILs before pre-operative chemotherapy (POC) in breast cancer and retrospectively analyzed the correlation between CCBs and TILs or prognosis. METHODS: Of the patients treated with POC, 338 who had evaluable TILs were enrolled in this study. The correlations among TILs were evaluated according to standard methods, and CCB use and prognosis were investigated retrospectively. RESULTS: Before POC, 65 patients (19.2%) took AHTs (CCBs: 41/338, 12.1%). The TIL density was significantly lower among patients administered CCBs for the group of all patients and for patients with TNBC (p = 0.040, p = 0.009, respectively). Additionally, patients with TNBC who were administered CCBs showed significantly lower response rates for POC (p = 0.040). In all patients receiving POC, no significant differences in disease-free survival (DFS) or overall survival (OS) were observed in patients administered CCBs (p = 0.712, p = 0.478, log-rank tests, respectively). Furthermore, no significant differences were found, even in patients with TNBC (DFS: p = 0.441, OS: p = 0.727, log-rank tests, respectively). CONCLUSIONS: In patients with TNBC undergoing treatment for hypertension with CCBs, TILs in the needle biopsy specimens before treatment were significantly lower, and the response rate of POC was not sufficient. Thus, the immunosuppressive effects of CCBs may also affect the immune microenvironment.


Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Imunossupressores/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Adulto , Idoso , Biópsia por Agulha , Contagem de Células , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/patologia , Adulto Jovem
18.
Gynecol Oncol ; 154(2): 426-431, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31178150

RESUMO

OBJECTIVE: To examine associations between post-diagnosis use of antihypertensive (AH) medications including thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACEIs), beta blockers (BBs) [both non-selective (NSBBs) and selective (SBBs)] and calcium channel blockers (CCBs) and ovarian cancer-specific survival. METHODS: This cohort study used SEER-Medicare data on 2195 women 66+ years of age who were diagnosed with ovarian cancer during 2007-2012 and who survived for at least 12 months. Use of an AH class was defined as two or more fills during the year after diagnosis. Ovarian cancer-specific death was assessed starting one year after diagnosis and continued through the end of 2013. Associations between AH use and ovarian cancer-specific mortality were assessed using Cox proportional hazard models, comparing users of a given class of AH to non-AH users. RESULTS: Overall, 718 (33%), 690 (31%), 521 (24%), 154 (7%) of women used a TD, ACEI, BB, or CCB, respectively, with some women (48%) using more than one class of drug. Ovarian cancer-specific mortality was found to be lower among women who used an ACEI (adjusted hazard ratio [aHR] 0.76, 95% confidence interval [CI] 0.63-0.92), a TD (aHR 0.82, 95%CI 0.68-0.99), or a NSBB (aHR 0.60, 95%CI 0.43-0.83), but no such association was seen in women who took a SBB or CCB. CONCLUSION: We observed that women who took certain forms of an AH medication during the year following a diagnosis of ovarian cancer were thereafter at a relatively reduced risk of dying from their disease. However, the potential for residual confounding by disease severity argues for a cautious interpretation.


Assuntos
Carcinoma Epitelial do Ovário/mortalidade , Hipertensão/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Carcinoma Epitelial do Ovário/complicações , Carcinoma Epitelial do Ovário/terapia , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão/complicações , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/terapia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Estados Unidos/epidemiologia
19.
J Ethnopharmacol ; 242: 112039, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31252093

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Parsley (Petroselinum crispum; P. crispum) is among the popular aromatic vegetables and a part of the daily diet in the Mediterranean area. This plant is widely used in alternative medicine as a remedy against hypertension. THE AIM OF THE STUDY: The aim of the study was to evaluate the antihypertensive activity of the aqueous extract of this plant. MATERIAL AND METHODS: In the current study, the aqueous extract of the aerial parts of parsley (AEPC) was prepared and its antihypertensive activity was evaluated using in vivo and in vitro studies. In the in vivo investigation, anesthetized L-NAME-hypertensive and normotensive rats received orally AEPC (160 mg/kg) during 6 h for the acute experiment and during seven days for the sub-chronic treatment. Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were recorded using a tail cuff and a computer-assisted monitoring device. Concerning the in vitro investigation, isolated thoracic aortic rings were suspended in a tissue bath and the tension changes were recorded to a data acquisition system. RESULTS: The results indicated that AEPC extract decreased the systolic, diastolic, mean arterial blood pressure in normotensive and hypertensive rats. The data revealed that parsley extract exerts its hypotensive effects through vasodilatory properties via an endothelium-independent pathway. More interestingly, the study demonstrated here that the vasorelaxing ability of AEPC is exerted through both Voltage Operated and Receptor Operated Calcium Channels (VOCC and ROCC). CONCLUSION: The study illustrates the beneficial action of P. crispum as an antihypertensive agent.


Assuntos
Anti-Hipertensivos , Bloqueadores dos Canais de Cálcio , Canais de Cálcio/fisiologia , Hipertensão/tratamento farmacológico , Petroselinum , Extratos Vegetais , Vasodilatadores , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Aorta/efeitos dos fármacos , Aorta/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Masculino , NG-Nitroarginina Metil Éster , Componentes Aéreos da Planta , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos Wistar , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico
20.
Hypertension ; 74(2): 413-420, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31203725

RESUMO

Cerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled study investigated how 6 months of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mild-to-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest including the hippocampus. Fifty-eight patients were randomly assigned (29 in each group), of whom 22 in both groups had no magnetic resonance exclusion criteria and were medication compliant over 6 months. Mean age was 72.8±6.2 years, mean mini-mental state examination was 20.4±3.4. Nilvadipine treatment lowered systolic blood pressure (Δ=-11.5 [95% CI, -19.7 to -3.2] mm Hg; P<0.01), while whole-brain gray-matter CBF remained stable (Δ=5.4 [95% CI, -6.4 to 17.2] mL/100 g per minute; P=0.36). CBF in the hippocampus increased (left: Δ=24.4 [95% CI, 4.3-44.5] mL/100 g per minute; P=0.02; right: Δ=20.1 [95% CI, -0.6 to 40.8] mL/100 g per minute; P=0.06). There was no significant change in CBF in the posterior cingulate cortex (Δ=5.2 [95% CI, -16.5 to 27.0] mL/100 g per minute; P=0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressure and increased CBF in the hippocampus, whereas other regions showed stable or small nonsignificant increases in CBF. These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02017340.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Nifedipino/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Países Baixos , Nifedipino/uso terapêutico , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Ultrassonografia Doppler/métodos
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