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1.
Expert Opin Investig Drugs ; 29(1): 1-4, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31825681

RESUMO

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


Assuntos
Taquicardia Paroxística/tratamento farmacológico , Taquicardia Supraventricular/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/farmacologia , Humanos , Sprays Nasais , Qualidade de Vida , Taquicardia Paroxística/fisiopatologia , Taquicardia Supraventricular/fisiopatologia , Fatores de Tempo
2.
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
3.
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
4.
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
5.
Rev Cardiovasc Med ; 20(2): 91-98, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31345001

RESUMO

A meta-analysis was performed to compare the antihypertensive efficacy of morning and evening dosing. Database of Pubmed, Embase, Cochrane, Web of Science CNKI, VIP, and Wanfang were searched up to December 2018. A total of 19 randomized control trials and 1215 participants were included in this meta-analysis. Administration time of amlodipine did not affect the office blood pressure (RR = -0.03, 95% CI -0.93-0.88, P = 0.96), daytime blood pressure (RR = -0.30, 95% CI -1.05-0.46, P = 0.44), 24 h mean blood pressure (RR = 1.15, 95% CI -0.39-2.70, P = 0.14), or heart rate (RR = 0.11, 95% CI -1.22-1.45, P = 0.87). Administration of amlodipine in the evening could significantly reduce the nighttime blood pressure (RR = 2.04, 95% CI 1.27-2.81, P < 0.00001), increased non-dipper alteration (RR = 0.51, 95% CI 0.41-0.63, P < 0.00001), and contained better anti-hypertension efficacy (RR = 0.64, 95% CI 0.55-0.74, P < 0.00001). For patients with hypertension, especially for non-dipper hypertension, taking amlodipine in the evening will be more beneficial. Better quality trials conducted in different regions and with larger sample size are necessary to verify the conclusion of this study.


Assuntos
Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Hipertensão/tratamento farmacológico , Anlodipino/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Cronoterapia Farmacológica , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
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
7.
J UOEH ; 41(2): 145-151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31292358

RESUMO

Constipation is very common and can be caused by adverse drug reactions as a result of many drugs. While the adverse effects of several medications such as opioids and anticholinergic agents are well established and well known, other commonly prescribed drugs, such as hypnotics, are less well understood. This review presents the results of an analysis of the relationship between constipation and drugs.


Assuntos
Antagonistas Colinérgicos/efeitos adversos , Constipação Intestinal/induzido quimicamente , Hipnóticos e Sedativos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticonvulsivantes/efeitos adversos , Antidepressivos Tricíclicos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Diuréticos/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Parassimpatolíticos/efeitos adversos
8.
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
9.
J Clin Pharm Ther ; 44(5): 813-814, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31211437

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Over the counter supplements are often taken for granted during medication reconciliation in the emergency department. Supplements are not regulated by FDA, and some can be potentially dangerous. CASE SUMMARY: We report a case of thyrotoxicosis secondary to over the counter bovine thyroid supplements. Our patient presented with atrial fibrillation with rapid ventricular response refractory to calcium channel blockers. Had we not known about the supplement, the course of treatment would have been different with potential adverse outcome. WHAT IS NEW AND CONCLUSION: Natural thyroid supplements are marketed as over the counter products and are largely unregulated. Thyroid extracts have been found to have disparaging inconsistencies in composition, delivering anywhere from non-existent to supratherapeutic doses. Thyroid supplements should be regulated considering the potential side effects.


Assuntos
Fibrilação Atrial/induzido quimicamente , Bloqueadores dos Canais de Cálcio/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Medicamentos sem Prescrição/efeitos adversos , Crise Tireóidea/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Tireotoxicose
11.
J Stroke Cerebrovasc Dis ; 28(8): 2155-2158, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103551

RESUMO

OBJECTIVE: To determine adherence to nimodipine administration in patients admitted with aneurysmal subarachnoid hemorrhage (aSAH). BACKGROUND: Oral nimodipine (60 mg every 4 hours for 21 days) is recommended by the national guidelines for aSAH. A Cochrane systematic review has determined that nimodipine reduces the risk of cerebral ischemia and is currently the only effective drug for the prevention of vasospasm in aSAH patients. DESIGN/METHODS: We retrospectively analyzed 109 patients with aSAH admitted to the Neurosciences Intensive Care Unit (NICU) at a tertiary care medical center between 2010 and 2013. Nimodipine-prescribing patterns, days of therapy completed, and adverse effects were tabulated. Patients not initiated on nimodipine and reasons for prematurely stopping therapy were noted. RESULTS: One hundred two (93%) patients with aSAH were started on oral nimodipine upon admission to the NICU. Early death (3%) and hypotension (1%) were reasons why patients were not started on nimodipine. Only 36 (33%) patients received nimodipine, 60 mg orally every 4 hours for 21 days. In 26 patients (39%), the dose of nimodipine was reduced because of excessive drops in blood pressure. Transient discontinuation occurred in 2 (2%) patients. Thirty one (47%) patients were discharged from the hospital before 21 days and nimodipine was not ordered to continue at home. CONCLUSION: We found that the majority of patients with aSAH in our practice did not complete 21 days of nimodipine. Hypotension was mostly responsible for dosing change or discontinuation.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Nimodipina/administração & dosagem , Padrões de Prática Médica , Hemorragia Subaracnóidea/tratamento farmacológico , Vasodilatadores/administração & dosagem , Administração Oral , Adulto , Idoso , Bloqueadores dos Canais de Cálcio/efeitos adversos , Esquema de Medicação , Feminino , Fidelidade a Diretrizes , Humanos , Hipotensão/induzido quimicamente , Hipotensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nimodipina/efeitos adversos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Padrões de Prática Médica/tendências , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Vasodilatadores/efeitos adversos
12.
Artigo em Inglês | MEDLINE | ID: mdl-31013922

RESUMO

Unlike chyloperitoneum associated with clinical conditions including cancer, cirrhosis, and traumatic surgery, calcium channel blocker (CCB)-associated chyloperitoneum is rarely discussed in comprehensive studies on chyloperitoneum. We aimed to investigate the prevalence and characteristics of CCB-associated chyloperitoneum in peritoneal dialysis (PD) patients. The MEDLINE, Embase, CENTRAL, CiNii, and RISS databases were systematically searched for clinical studies on CCB-associated chyloperitoneum in PD patients published up to 31 July 2018. A total of 17 studies (four cohort studies, one case series, and 12 case reports) were selected. Eight CCBs, namely amlodipine, benidipine, diltiazem, lercanidipine, manidipine, nifedipine, nisoldipine, and verapamil, were reported to be associated with chyloperitoneum; manidipine and lercanidipine were the most frequently reported. The average prevalence of chyloperitoneum for lercanidipine was 25.97% in three cohort studies, two of which had a moderate or high risk of bias. Most of the studies revealed chyloperitoneum development within 4 days of initiation of CCB therapy and chyloperitoneum disappearance within 24 h of CCB withdrawal. The results of this study emphasise on the need for awareness among healthcare professionals regarding CCB-associated chyloperitoneum in PD patients. Further studies elucidating the causality and clinical implication of CCB-associated chyloperitoneum are needed.


Assuntos
Bloqueadores dos Canais de Cálcio/efeitos adversos , Ascite Quilosa/induzido quimicamente , Diálise Peritoneal , Humanos , Fatores de Risco
13.
Am J Cardiovasc Drugs ; 19(3): 313-323, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30919249

RESUMO

BACKGROUND: Angiotensin-converting enzyme inhibitors and calcium channel blockers in combination are widely recommended in hypertension guidelines. The advantages of single-pill combinations (SPCs) are increasingly recognized, so a dosage-adapted combination of perindopril and amlodipine was developed for the initial management of hypertension. OBJECTIVE: This randomized trial evaluated the blood pressure (BP)-lowering efficacy of four incremental doses of perindopril/amlodipine SPC in adults with mild-to-severe hypertension. METHODS: Eligible patients (N = 1617) were randomized to SPC perindopril 3.5 mg/amlodipine 2.5 mg (i.e., 3.5/2.5 mg) daily, uptitrating as required on a monthly basis up to 14/10 mg until BP < 140/90 mmHg (< 130/80 mmHg in patients with diabetes). The primary endpoint (proportion with controlled BP at each uptitrated dose) was evaluated at 6 months, and safety was evaluated at 9 months; 24-h ambulatory BP measurement and BP variability were also investigated. Control-arm participants (n = 1653) were randomized to irbesartan 150 mg daily, uptitrating over 3 months to irbesartan/hydrochlorothiazide 300/25 mg. RESULTS: Significant increases in BP control were observed with each dosage increment of perindopril/amlodipine, which was well tolerated, rising from 21% (3.5/2.5 mg) to 30% (7/5 mg), 37% (14/5 mg), and 42% (14/10 mg) after 1, 2, 3, and 6 months, respectively. Reductions in mean systolic and diastolic BP occurred with each incremental dose of perindopril/amlodipine. After 6 months, mean BP had fallen by 24.8/10.8 mmHg. Irbesartan-based therapy reduced clinic and 24-h BP similarly to perindopril/amlodipine, but perindopril/amlodipine reduced BP variability more in comparison. CONCLUSIONS: Incremental uptitration with dosage-adapted perindopril/amlodipine SPC is a safe and effective strategy for managing hypertension. TRIAL REGISTRATION: EudraCT (No. 2006-005799-42).


Assuntos
Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Perindopril/administração & dosagem , Idoso , Anlodipino/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Perindopril/efeitos adversos , Índice de Gravidade de Doença
14.
Cochrane Database Syst Rev ; 2: CD001928, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30758052

RESUMO

BACKGROUND: The sudden loss of blood supply in ischemic stroke is associated with an increase of calcium ions within neurons. Inhibiting this increase could protect neurons and might reduce neurological impairment, disability, and handicap after stroke. OBJECTIVES: To assess the effects of calcium antagonists for reducing the risk of death or dependency after acute ischemic stroke. We investigated the influence of different drugs, dosages, routes of administration, time intervals after stroke, and trial design on the outcomes. SEARCH METHODS: The evidence is current to 6 February 2018. We searched the Cochrane Stroke Group Trials Register (6 February 2018), Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), MEDLINE Ovid (1950 to 6 February 2018), Embase Ovid (1980 to 6 February 2018), and four Chinese databases (6 February 2018): Chinese Biological Medicine Database (CBM-disc), China National Knowledge Infrastructure (CNKI), Chinese Scientific Periodical Database of VIP information, and Wanfang Data. We also searched the following trials registers: ClinicalTrials.gov, EU Clinical Trials Register, Stroke Trials Registry, ISRCTN registry, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Registry, and we contacted trialists and researchers. SELECTION CRITERIA: Randomized controlled trials comparing a calcium antagonist versus control in people with acute ischemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the quality of the evidence. We used death or dependency at the end of long-term follow-up (at least three months) in activities of daily living as the primary outcome. We used standard Cochrane methodological procedures. MAIN RESULTS: We included 34 trials involving 7731 participants. All the participants were in the acute stage of ischemic stroke, and their age ranged from 18 to 85 years, with the average age ranging from 52.3 to 74.6 years across different trials. There were more men than women in most trials. Twenty-six trials tested nimodipine, and three trials assessed flunarizine. One trial each used isradipine, nicardipine, PY108-608, fasudil, and lifarizine. More than half of these trials followed participants for at least three months. Calcium antagonists showed no effects on the primary outcome (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.98 to 1.13; 22 trials; 22 studies; 6684 participants; moderate-quality evidence) or on death at the end of follow-up (RR 1.07, 95% CI 0.98 to 1.17; 31 trials; 7483 participants; moderate-quality evidence). Thirteen trials reported adverse events, finding no significant differences between groups. Most trials did not report the allocation process or how they managed missing data, so we considered these at high risk of selection and attrition bias. Most trials reported double-blind methods but did not state who was blinded, and none of the trial protocols were available. AUTHORS' CONCLUSIONS: We found no evidence to support the use of calcium antagonists in people with acute ischemic stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Vasodilatadores/uso terapêutico , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/mortalidade , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/efeitos adversos , Feminino , Flunarizina/administração & dosagem , Flunarizina/efeitos adversos , Flunarizina/uso terapêutico , Humanos , Isradipino/administração & dosagem , Isradipino/efeitos adversos , Isradipino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nimodipina/administração & dosagem , Nimodipina/efeitos adversos , Nimodipina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Vasodilatadores/administração & dosagem , Adulto Jovem
15.
Drugs ; 79(4): 463-468, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30778848

RESUMO

Mirogabalin besylate (hereafter mirogabalin) [Tarlige®] is an orally administered gabapentinoid developed by Daiichi Sankyo for the treatment of peripheral neuropathic pain (PNP), including diabetic PNP and post-herpetic neuralgia. The drug binds to and modulates the α2δ-1 subunit of the voltage-gated calcium channels widely found in the nervous system in areas that mediate pain transmission and processing. Mirogabalin has a unique binding profile and long duration of action. The drug is approved in Japan for the treatment of PNP and is in clinical development for this indication elsewhere in Asia. Clinical development of the drug for fibromyalgia pain was discontinued in the USA and EU after the primary endpoint was not met in phase 3 trials. No recent reports of development have been identified for PNP in the USA or India or for fibromyalgia pain in Australia, India, New Zealand, Russia, Argentina, Belarus, Chile, Colombia, Israel, Mexico, Switzerland, Canada, Serbia or South Africa. This article summarizes the milestones in the development of mirogabalin leading to this first approval for PNP.


Assuntos
Compostos Bicíclicos com Pontes/uso terapêutico , Neuralgia/tratamento farmacológico , Dor/tratamento farmacológico , Compostos Bicíclicos com Pontes/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio/metabolismo , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Aprovação de Drogas , Humanos , Japão , Neuralgia/complicações , Neuralgia Pós-Herpética/tratamento farmacológico , Dor/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Intern Med ; 58(12): 1791-1794, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30799349

RESUMO

We encountered a case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) caused by duloxetine, serotonin and norepinephrine reuptake inhibitor (SNRI). A 74-year-old woman complaining of severe lethargy was transferred to our emergency department. Her serum sodium level was 109 mEq/L. Plasma hypo-osmolality with urine normo-osmolality was observed, indicating SIADH. Her essential hypertension had long been treated with telmisartan, and she had just started duloxetine 20 mg/day for chronic musculoskeletal pain 4 days prior to admission. On prescribing duloxetine in the primary care setting, clinicians should be aware of the possibility of duloxetine-induced hyponatremia, particularly in combination with telmisartan.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Cloridrato de Duloxetina/efeitos adversos , Hiponatremia/induzido quimicamente , Síndrome de Secreção Inadequada de HAD/induzido quimicamente , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Cloridrato de Duloxetina/administração & dosagem , Feminino , Humanos
17.
Obstet Gynecol Surv ; 74(1): 50-55, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30648727

RESUMO

Importance: Preterm delivery represents an important cause of infant morbidity and mortality. Various tocolytics have been studied with the objective of stopping preterm labor, increasing gestational age at delivery, and preventing complications related to preterm birth. Objective: This review aims to summarize the major classes of tocolytics and review the evidence regarding use of each. Evidence Acquisition: A PubMed search of the following terms was performed to gather relevant data: "tocolytic," "preterm labor," "preterm delivery," "PPROM," "magnesium," "indomethacin," "nifedipine," and "betamimetics." Results: The benefits and risks of nonsteroid anti-inflammatory drugs, calcium channel blockers, magnesium, and betamimetics are reviewed. Calcium channel blockers afford superior outcomes in terms of prolonging gestation and decreasing neonatal morbidity and mortality with the fewest adverse effects. Conclusions and Relevance: Tocolytics, particularly calcium channel blockers, may provide benefit to pregnant women and their infants. Their use should be tailored to the particular clinical circumstances of the patient and used in conjunction with other management strategies (e.g., administration of corticosteroids for fetal lung maturation or magnesium for neuroprotection and transfer to a tertiary medical center). Further research and professional guidelines are needed on optimal use of these agents.


Assuntos
Trabalho de Parto Prematuro/tratamento farmacológico , Nascimento Prematuro/prevenção & controle , Tocólise/métodos , Tocolíticos/administração & dosagem , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/efeitos adversos , Feminino , Ruptura Prematura de Membranas Fetais/tratamento farmacológico , Idade Gestacional , Humanos , Gravidez , Tocolíticos/efeitos adversos
18.
Clin Toxicol (Phila) ; 57(1): 31-35, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30484705

RESUMO

BACKGROUND: Most Americans take at least one medication on a daily basis. Inadvertently ingesting a double-dose of a medication with a narrow therapeutic index may lead to adverse effects. When a patient or medical professional contacts the local poison center after an overdose, a poison specialist fields the incoming information and, depending on the caller, provides specific recommendations. We sought to determine which medication classes were most likely to lead to significant adverse outcomes when an extra dose was ingested. METHODS: This was a retrospective review of all double-dose medication ingestions reported to the California Poison Control System (CPCS) between January 2006 and December 2015. Inclusion criteria were single-instance, single-medication ingestions where the dose was known. All ages and both sexes were included. We evaluated generalized outcomes per AAPCC criteria stratified as no effect, minor, moderate, major or death. We also documented specific symptoms and interventions noted by the poison control specialists. RESULTS: Out of 1286 cases, 876 ingestions met the inclusion criteria. Medications with antihypertensive and behavior modulating effects each accounted for over a third of all moderate and major effects. The medications/medication classes implicated in the 12 major outcomes included propafenone, beta blockers (ßBs), calcium channel blockers (CCBs), bupropion, and tramadol. Of these, vasoactive medications were associated with the most severe effects requiring cardiac pacing and vasopressor drips. Analgesics, antimicrobials, and anti-allergy medications were well tolerated. There were no deaths. CONCLUSIONS: Major adverse outcomes after a double dose ingestion were rare. Most double dose medication ingestions can be safely monitored at home, albeit with a few exceptions. Vigilance is warranted in cases of ßB and CCB ingestion due to the risk of hemodynamic collapse or seizures with tramadol and bupropion.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Overdose de Drogas/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Centros de Controle de Intoxicações/estatística & dados numéricos , Antagonistas Adrenérgicos beta/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Overdose de Drogas/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Humanos , Estudos Retrospectivos , Estados Unidos/epidemiologia
20.
Clin Drug Investig ; 39(1): 85-96, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30368658

RESUMO

BACKGROUND AND OBJECTIVE: Tylerdipine hydrochloride (KBP-5660) is a novel L/T-type dual calcium channel blocker developed for the treatment of hypertension. We aimed to study the pharmacokinetics, safety and tolerability of tylerdipine in healthy Chinese subjects. METHODS: Two double-blind, randomized, dose-escalation studies were conducted that included a total of 88 healthy subjects: (1) a single-ascending dose (SAD) study; and (2) a multiple-ascending dose (MAD) study. In the SAD study, 64 subjects were randomly assigned to receive a single dose of 0.5, 2.5, 5, 10, 15, 20, 25, or 30 mg of tylerdipine or placebo. In the MAD study, 24 subjects were randomly assigned to receive 10 or 20 mg of tylerdipine or placebo once daily for 9 days. Blood samples were collected at the designated time points for pharmacokinetic analyses. Safety assessments were conducted throughout the study. RESULTS: Following a single oral dose of tylerdipine of 5-30 mg, the mean maximum plasma concentration (Cmax) increased from 0.9993 to 10.11 ng/ml; mean area under the plasma-concentration curve (AUC) from time zero to 72 h increased from 4.332 to 73.95 h·ng/ml. AUC increased in a greater than dose-proportional manner, whereas Cmax exhibited a rough but non-typical dose-proportionality increase. In the MAD study, steady-state conditions were achieved after 1 week of daily dosing in both dose groups. Accumulation of tylerdipine was low, with accumulation ratios (RAUC) of less than 1.65. All adverse events were assessed as mild or moderate. CONCLUSION: Tylerdipine hydrochloride was safe and well tolerated. The exposure (AUC) of tylerdipine over the dose range of 5-30 mg increased in a greater than dose-proportional manner, while Cmax exhibited a rough but non-typical dose proportionality increase. A slight accumulation of tylerdipine was observed following multiple dosing. STUDY REGISTRATIONS: CTR20140862 and CTR20150660.


Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Nitrobenzenos/administração & dosagem , Adulto , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/farmacocinética , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Nitrobenzenos/efeitos adversos , Nitrobenzenos/farmacocinética , Adulto Jovem
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