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1.
Medicine (Baltimore) ; 99(1): e18541, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31895792

RESUMEN

Perioperative hypertension is a common occurrence in the neurosurgical population, where 60% to 90% of the patients require treatment for blood pressure (BP) control. Nicardipine and clevidipine have been commonly used in neurocritical settings. This retrospective, observational study assessed the effectivity of the administration of clevidipine after nicardipine treatment failure in neurosurgical patients.We retrospectively reviewed the medical charts of adult patients who were admitted to our neurosurgical department and received clevidipine after nicardipine treatment failure for the control of BP. The primary effectivity outcome was the comparison of the percentage of time spent at targeted SBP goals during nicardipine and clevidipine administration, respectively.A total of 12 adult patients treated with clevidipine after nicardipine treatment failure and were included for data analysis. The median number of events that required dose-titration was 20.5 vs 17 during the administration of nicardipine and clevidipine, respectively (P = .534). The median percentage of time spent at targeted SBP goal was 76.2% during the administration of nicardipine and 93.4% during the administration of clevidipine (P = .123).Our study suggests that clevidipine could be an alternative effective drug with an acceptable benefit/risk ratio in the neurosurgical population that fails to achieve BP control with nicardipine treatment.


Asunto(s)
Bloqueadores de los Canales de Calcio/administración & dosificación , Hipertensión/tratamiento farmacológico , Complicaciones Intraoperatorias/tratamiento farmacológico , Procedimientos Neuroquirúrgicos/efectos adversos , Piridinas/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Hipertensión/etiología , Complicaciones Intraoperatorias/etiología , Masculino , Persona de Mediana Edad , Nicardipino/uso terapéutico , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento
2.
Expert Opin Investig Drugs ; 29(1): 1-4, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31825681

RESUMEN

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.


Asunto(s)
Taquicardia Paroxística/tratamiento farmacológico , Taquicardia Supraventricular/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/farmacología , Humanos , Rociadores Nasales , Calidad de Vida , Taquicardia Paroxística/fisiopatología , Taquicardia Supraventricular/fisiopatología , Factores de Tiempo
3.
Urologiia ; (5): 48-52, 2019 Dec.
Artículo en Ruso | MEDLINE | ID: mdl-31808632

RESUMEN

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.


Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Citocinas/sangre , Dihidropiridinas/uso terapéutico , Riñón/efectos de los fármacos , Nefrolitiasis/cirugía , Fármacos Neuroprotectores/uso terapéutico , Urolitiasis/cirugía , Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Bloqueadores de los Canales de Calcio/administración & dosificación , Dihidropiridinas/administración & dosificación , Tasa de Filtración Glomerular , Humanos , Fármacos Neuroprotectores/administración & dosificación , Resultado del Tratamiento
4.
S Afr Med J ; 109(9): 635-638, 2019 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-31635586

RESUMEN

Calcium channel blockers (CCBs) are commonly used in South Africa (SA) in the management of hypertension and other cardiovascular disease. Their ubiquitous availability makes them a common agent in drug overdose (OD), whether through accidental ingestion or deliberate self-harm. It is essential that medical practitioners know how to recognise and manage CCB OD, as severe CCB OD is often fatal. As there is a lack of local literature in SA, we highlight the general principles of management of CCB OD, as well as complications and problems that may be encountered during treatment. This narrative review is based on existing clinical guidelines, retrospective studies and systematic reviews on the emergency management of CCB OD. High-dose insulin euglycaemic therapy has become the mainstay of treatment in severe CCB OD. The rationale, the recommended protocol for its use and its adverse effects are described.


Asunto(s)
Bloqueadores de los Canales de Calcio/envenenamiento , Sobredosis de Droga/terapia , Tratamiento de Urgencia/métodos , Bloqueadores de los Canales de Calcio/administración & dosificación , Enfermedades Cardiovasculares/tratamiento farmacológico , Humanos , Hipertensión/tratamiento farmacológico , Insulina/administración & dosificación , Guías de Práctica Clínica como Asunto , Sudáfrica
5.
Drug Des Devel Ther ; 13: 2427-2436, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31413542

RESUMEN

Background: Mortality rates increase due to iron deposition in the cardiac muscles of thalassemia major (TM) patients. Iron overload cardiomyopathy could be treated with a combination therapy of an iron chelator and an L-type calcium channel blocker. We designed a randomized controlled study to assess the potential of amlodipine, alongside chelation, in reducing myocardial iron concentration in TM patients compared with a placebo. Objectives: This study aims to estimate the change in myocardial iron concentration (MIC) determined by magnetic resonance imaging after 6 months of treatment with amlodipine, as well as measuring the changes in the secondary outcomes (liver iron concentration (LIC), serum ferritin level (SF), and left ventricle ejection fraction (LVEF)) of study participants. Methods: A single, randomized, placebo-controlled trial was performed in 40 ß-Thalassemia major patients aged between 6 and 20 years old, who received either oral amlodipine 2.5-5 mg/day or a placebo, in addition to a Deferasirox chelation regimen in a 1:1 allocation ratio. Results: After 6 months, a significant reduction was noted in the MIC of patients receiving amlodipine (n=20), compared with the patients receiving the placebo (n=20). At baseline, the mean was 0.76±0.11 mg/g dry weight, while at 6 months, the mean was 0.51±0.07 mg/g dry weight (p<0.001). Also, there was a significant change in the myocardial T2* after 6 months; the amlodipine increased the myocardial T2* from 40.63±5.45 ms at baseline to 43.25±5.35 ms (p<0.001). However, amlodipine did not significantly affect the secondary outcomes by the end of the study. Conclusion: The addition of amlodipine to the standard chelation therapy in transfusion-dependent thalassemia major patients improves myocardial iron overload without increasing the adverse effects.


Asunto(s)
Amlodipino/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Talasemia beta/tratamiento farmacológico , Adolescente , Adulto , Amlodipino/administración & dosificación , Bloqueadores de los Canales de Calcio/administración & dosificación , Niño , Femenino , Humanos , Hierro/análisis , Quelantes del Hierro/administración & dosificación , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos , Adulto Joven
6.
J Neurosci Nurs ; 51(5): 238-242, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31469704

RESUMEN

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is a type of stroke that is life threatening with high rates of mortality, and many survivors are left with permanent neurologic deficits. Nimodipine is the treatment of choice for aSAH with the goal of reduction of delayed cerebral ischemia. It is the only evidence-based medication that has been shown to have improved outcomes for delayed cerebral ischemia; therefore, it is important for neuroscience nurses to be knowledgeable of the pharmacology and pharmacogenomics properties of this medication, including cytochrome P450 (CYP450) enzymes. METHODS AND RESULTS: This article reviews the CYP450 enzyme system including a review of the pharmacotherapy and pharmacogenomics of nimodipine for patients with aSAH illustrated with case study of a patient with abnormal drug metabolism. CONCLUSION: CYP450 enzymes can be inhibited or induced by multiple medications resulting in clinically significant differences in drug metabolism. Food and Drug Administration-approved medication nimodipine is the only medication shown to improve outcomes in patients with aSAH. Hence, it is important to have awareness of potential drug-to-drug interactions and pharmacogenomics of nimodipine when caring for critically ill patients with aSAH.


Asunto(s)
Bloqueadores de los Canales de Calcio/administración & dosificación , Sistema Enzimático del Citocromo P-450/metabolismo , Nimodipina/administración & dosificación , Farmacogenética , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/tratamiento farmacológico , Administración Oral , Adulto , Isquemia Encefálica/etiología , Isquemia Encefálica/prevención & control , Esquema de Medicación , Adhesión a Directriz , Humanos , Masculino
7.
Rev Cardiovasc Med ; 20(2): 91-98, 2019 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-31345001

RESUMEN

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.


Asunto(s)
Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Hipertensión/tratamiento farmacológico , Amlodipino/efectos adversos , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Cronoterapia de Medicamentos , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
8.
Gen Physiol Biophys ; 38(3): 227-235, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31184309

RESUMEN

The present in vitro study examined whether lipid emulsion attenuates the vasodilation evoked by toxic doses of calcium channel blockers (bepridil, verapamil, nifedipine and diltiazem) via their partitioning into the lipid phase. The effects of the calcium channel blockers alone, the lipid emulsion and calcium channel blocker mixture, and the centrifuged aqueous extract (CAE) obtained from ultracentrifugation of the lipid emulsion and calcium channel blocker mixture on isolated endothelium-denuded rat aortas precontracted with phenylephrine were observed. The effects of lipid emulsion on calcium channel blocker concentration in the Krebs solution were examined using ultraperformance liquid chromatography. A mixture of lipid emulsion with either bepridil or verapamil and the corresponding CAE more effectively attenuated vasodilation than either bepridil or verapamil alone, whereas the vasodilation induced by the mixture of lipid emulsion and either bepridil or verapamil was not significantly different from that induced by the corresponding CAE. The magnitude of the lipid emulsion-mediated reduction in vasodilation and calcium channel blocker concentration was as follows: bepridil > verapamil > nifedipine or diltiazem. These results suggest that lipid emulsion attenuates vasodilation induced by a toxic dose of bepridil and verapamil, seemingly through partitioning of the calcium channel blocker into the lipid phase.


Asunto(s)
Bloqueadores de los Canales de Calcio/química , Bloqueadores de los Canales de Calcio/toxicidad , Lípidos/química , Vasodilatación/efectos de los fármacos , Animales , Bloqueadores de los Canales de Calcio/administración & dosificación , Emulsiones , Ratas
9.
J Pharmacol Sci ; 140(2): 193-196, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31235271

RESUMEN

We tested whether NNC 55-0396 (NNC), a T-type calcium channel (T-channel) blocker, reduces the brain injury caused by middle cerebral artery occlusion and reperfusion (MCAO/R) in mice. NNC, administered i.c.v. before the occlusion, greatly reduced the MCAO/R-induced brain infarct and neurological dysfunctions, although it, given toward the end of occlusion, was less effective. Systemic administration of NNC before the occlusion also attenuated the infarct and neurological dysfunctions. Our data imply that blood-brain-barrier-permeable T-channel blockers such as NNC are capable of reducing MCAO/R-induced brain damage, and that T-channels are involved in neuronal damage induced by ischemia rather than reperfusion.


Asunto(s)
Bencimidazoles/administración & dosificación , Lesiones Encefálicas/etiología , Lesiones Encefálicas/prevención & control , Bloqueadores de los Canales de Calcio/administración & dosificación , Ciclopropanos/administración & dosificación , Infarto de la Arteria Cerebral Media/complicaciones , Naftalenos/administración & dosificación , Daño por Reperfusión/complicaciones , Animales , Bencimidazoles/metabolismo , Barrera Hematoencefálica/metabolismo , Bloqueadores de los Canales de Calcio/metabolismo , Canales de Calcio Tipo T/fisiología , Ciclopropanos/metabolismo , Infusiones Intraventriculares , Infusiones Parenterales , Masculino , Ratones Endogámicos , Naftalenos/metabolismo , Factores de Tiempo
10.
Basic Clin Pharmacol Toxicol ; 125(4): 345-352, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31058419

RESUMEN

The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open-label, three-period, fixed-sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP-3174, an active metabolite of losartan, were assessed at steady-state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady-state (AUCτ , 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954-1.178)]. In addition, the exposure of EXP-3174 was not affected by amlodipine (AUCτ , 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891-1.027]). However, amlodipine significantly decreased the exposure of losartan at steady-state (AUCτ , 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813-0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co-administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.


Asunto(s)
Amlodipino/farmacocinética , Antihipertensivos/farmacocinética , Hemodinámica/efectos de los fármacos , Losartán/farmacocinética , Administración Oral , Adulto , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/farmacocinética , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/farmacocinética , Interacciones Farmacológicas , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Voluntarios Sanos , Humanos , Hipertensión/tratamiento farmacológico , Losartán/administración & dosificación , Losartán/efectos adversos , Masculino , Persona de Mediana Edad , República de Corea , Adulto Joven
11.
Ter Arkh ; 91(1): 101-107, 2019 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-31090380

RESUMEN

In conditions of climate warming with an increase in heat waves associated with an increase in cardiovascular morbidity and mortality, the particular interest is the effect of cardiovascular drugs on adaptation to high temperatures. The review reflects the results of European and domestic studies on the safety of therapy during long and short heat waves. Recommendations for the correction of therapy during this period are given. Self-control of blood pressure (SCAD) is a mandatory component of the therapy of arterial hypertension during heat waves. With the development of clinically significant hypotension, a reduction in the dose of antihypertensive drugs is necessary. It is recommended to start with a dose reduction and/or withdrawal of diuretics and nitrates. Not recommended the complete abolition of antihypertensive therapy because of the risk of hypertensive crises, characteristic of abnormal heat, as well as due to the increase in blood pressure when the weather changes and the temperature drops. With increasing blood pressure during heat waves, it is recommended to give preference to calcium channel antagonists, angiotensin converting enzyme inhibitors (ACE inhibitors) and selective beta-blockers. It is necessary to inform patients about the additional protective effect of statins in order to increase adherence to therapy. Patients taking diuretics require individual daily monitoring of fluid intake and body weight. An overview of recommendations on sanogenic behavior during heat waves is given. Details are considered rules for the use of air conditioning, methods of diagnosis of dehydration and drinking mode Keywords: heat waves, cardiovascular complications, preventive measures.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Bloqueadores de los Canales de Calcio/administración & dosificación , Enfermedades Cardiovasculares/tratamiento farmacológico , Calor Extremo/efectos adversos , Hipertensión/tratamiento farmacológico , Rayos Infrarrojos/efectos adversos , Antagonistas Adrenérgicos beta/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/mortalidad , Diuréticos/efectos adversos , Diuréticos/farmacología , Humanos , Estaciones del Año
12.
Pharm Biol ; 57(1): 306-309, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31060428

RESUMEN

CONTEXT: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with amlodipine (ALDP) for treating coronary heart disease. OBJECTIVE: This study investigated the effects of DST on the pharmacokinetics of ALDP and the potential mechanism. MATERIALS AND METHODS: The pharmacokinetics of ALDP (1 mg/kg) in male Sprague-Dawley rats (n = 6), with or without pretreatment of DST (100 mg/kg for 7 d), were investigated using LC-MS/MS. The effects of DST on the metabolic stability of ALDP were also investigated using rat liver microsomes (RLM). RESULTS: The results indicated that Cmax (16.25 ± 2.65 vs. 22.79 ± 2.35 ng/ml), AUC(0-t) (222.87 ± 59.95 vs. 468.32 ± 69.87 n gh/ml), and t1/2 (10.60 ± 1.05 vs. 14.15 ± 1.59 h) decreased significantly when DST and ALDP were co-administered, which suggested that DST might influence the pharmacokinetic behaviour of ALDP when they are co-administered. The metabolic stability of ALDP was also decreased (23.6 ± 4.7 vs. 38.9 ± 5.2) with the pretreatment of DST. DISCUSSION AND CONCLUSIONS: This study indicated that DST could accelerate the metabolism of ALDP in RLM and change the pharmacokinetic behaviours of ALDP. Accordingly, these results showed that the herb-drug interaction between DST and ALDP might occur when they were co-administered. Therefore, the clinical dose of ALDP should be increased when DST and ALDP are co-administered.


Asunto(s)
Amlodipino/farmacocinética , Bloqueadores de los Canales de Calcio/farmacocinética , Medicamentos Herbarios Chinos/farmacología , Interacciones de Hierba-Droga , Salvia miltiorrhiza/química , Amlodipino/administración & dosificación , Amlodipino/sangre , Animales , Área Bajo la Curva , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/sangre , Cromatografía Liquida , Relación Dosis-Respuesta a Droga , Estabilidad de Medicamentos , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Masculino , Microsomas Hepáticos/metabolismo , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem
13.
J Stroke Cerebrovasc Dis ; 28(8): 2155-2158, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31103551

RESUMEN

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.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Nimodipina/administración & dosificación , Pautas de la Práctica en Medicina , Hemorragia Subaracnoidea/tratamiento farmacológico , Vasodilatadores/administración & dosificación , Administración Oral , Adulto , Anciano , Bloqueadores de los Canales de Calcio/efectos adversos , Esquema de Medicación , Femenino , Adhesión a Directriz , Humanos , Hipotensión/inducido químicamente , Hipotensión/fisiopatología , Masculino , Persona de Mediana Edad , Nimodipina/efectos adversos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/tendencias , Estudios Retrospectivos , Factores de Riesgo , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Vasodilatadores/efectos adversos
14.
Lancet ; 393(10181): 1657-1668, 2019 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-30935736

RESUMEN

Tetanus is a vaccine-preventable disease that still commonly occurs in many low-income and middle-income countries, although it is rare in high-income countries. The disease is caused by the toxin of the bacterium Clostridium tetani and is characterised by muscle spasms and autonomic nervous system dysfunction. Global vaccination initiatives have had considerable success but they continue to face many challenges. Treatment for tetanus aims to control spasms and reduce cardiovascular instability, and consists of wound debridement, antitoxin, antibiotics, and supportive care. Recent research has focused on intravenous magnesium sulphate and intrathecal antitoxin administration as methods of spasm control that can avoid the need for ventilatory support. Nevertheless, without access to mechanical ventilation, mortality from tetanus remains high. Even with such care, patients require several weeks of hospitalisation and are vulnerable to secondary problems, such as hospital-acquired infections.


Asunto(s)
Carga Global de Enfermedades , Tétanos , Administración Intravenosa , Bloqueadores de los Canales de Calcio/administración & dosificación , Femenino , Humanos , Sulfato de Magnesio/administración & dosificación , Masculino , Áreas de Pobreza , Embarazo , Índice de Severidad de la Enfermedad , Espasmo/tratamiento farmacológico , Tétanos/tratamiento farmacológico , Tétanos/epidemiología , Tétanos/prevención & control , Toxoide Tetánico/inmunología , Vacunación/estadística & datos numéricos
15.
World Neurosurg ; 127: e1104-e1111, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30980985

RESUMEN

BACKGROUND: Verapamil, a calcium-channel blocker, has shown promising results on cerebral vasospasm. However, it has not yet been accepted for treatment or prevention purposes because of the associated side effects. Although the effective results of nimodipine and nicardipine's intrathecal administration are well known, intrathecal verapamil has not been considered earlier. We used an experimental subarachnoid hemorrhage-induced vasospasm model for the evaluation of vasodilator and neuroprotective effects of intrathecal verapamil. METHODS: A total of 24 Sprague-Dawley rats were randomly divided into the following 3 groups: group 1 (sham), group 2 (subarachnoid hemorrhage), and group 3 (verapamil). A double hemorrhage method was used. Group 2 did not receive any treatment. Verapamil (Eporon, Dem Ilac, Turkey) at a dose of 1000 µg/kg was given intrathecally to group 3 rats. The animals were euthanized on day 7 of the procedure. Arterial wall thickness and lumen diameter in the basilar arterial cross-sectional areas, endothelin-1 serum level, oxidative stress index, and apoptosis were measured in all groups. RESULTS: In the verapamil group, wall thickness, endothelin-1 level, oxidative stress index, and apoptosis were found to be significantly lower than the subarachnoid hemorrhage group, but the lumen diameter was found to be greater. Intrathecal verapamil was found to decrease vasospasm parameters and apoptosis and increase the antioxidant and antiapoptotic pathways. CONCLUSIONS: Our findings suggest that intrathecal verapamil can prevent vasospasm, oxidative stress, and apoptosis after experimental subarachnoid hemorrhage.


Asunto(s)
Bloqueadores de los Canales de Calcio/administración & dosificación , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/patología , Verapamilo/administración & dosificación , Animales , Inyecciones Espinales , Masculino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Ratas , Ratas Sprague-Dawley , Resultado del Tratamiento , Vasodilatadores/administración & dosificación , Vasoespasmo Intracraneal/metabolismo
16.
Int J Cardiovasc Imaging ; 35(9): 1549-1555, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30941564

RESUMEN

The transient left atrial appendage (LAA) dysfunction after electrical cardioversion (CV), which is called as LAA-stunning, was found to be an important etiology of thrombus formation. The aim of the present study was to investigate the risk factors of LAA-stunning. This study included 134 patients who underwent catheter ablation for non-paroxysmal, non-valvular, and symptomatic atrial fibrillation (AF). Internal-CV was performed, and LAA emptying fraction (LAA-EF) was assessed using LAA-angiogram before and just after CV. LAA-stunning (defined as 10% reduction of LAA-EF after CV) was observed in 45/134 patients (34%). Patients in LAA-stunning group had longer duration of AF prior to CV, higher brain natriuretic peptide (BNP), higher prevalence of patients taking calcium blocker, larger left atrial (LA) diameter, elevated E wave, and larger LA volume than those in non LAA-stunning group. Multivariate analysis showed that longer duration of AF prior to CV (p = 0.015, OR 1.033 for 1 month extend, 95% CI 1.006-1.073) and elevated BNP (p = 0.038, OR 1.041 for each 10 pg/mL increase, 95% CI 1.001-1.009) were associated with LAA-stunning. In addition, all patients were divided into four groups based on the combination between duration of AF prior to CV and BNP; group 1 (low BNP/short-lasting AF), group 2 (high BNP/short-lasting AF), group 3 (low BNP/long-lasting AF), and group 4 (high BNP/long-lasting AF). The rate of LAA-stunning was the highest in the group 4 (55.6%). Elevated BNP and long duration of AF were associated with LAA stunning after electrical cardioversion.


Asunto(s)
Apéndice Atrial/fisiopatología , Fibrilación Atrial/terapia , Función del Atrio Izquierdo , Cardioversión Eléctrica/efectos adversos , Aturdimiento Miocárdico/etiología , Anciano , Antiarrítmicos/administración & dosificación , Apéndice Atrial/diagnóstico por imagen , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/fisiopatología , Biomarcadores/sangre , Bloqueadores de los Canales de Calcio/administración & dosificación , Esquema de Medicación , Ecocardiografía , Técnicas Electrofisiológicas Cardíacas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aturdimiento Miocárdico/diagnóstico por imagen , Aturdimiento Miocárdico/fisiopatología , Péptido Natriurético Encefálico/sangre , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba
17.
Indian Heart J ; 71(1): 32-38, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31000180

RESUMEN

BACKGROUND: Despite several decades of use of calcium channel blockers, the side effect of edema persists as a class effect, and its mechanism is unresolved. Amlodipine has effects on hemorheology (HR), and its hemodilutory property may partly contribute to its antihypertensive action. This aspect is not well studied, and the literature is sparse in this regard. OBJECTIVE: This experiment was planned to determine effect of a single-dose administration of amlodipine on HR parameters in normal human volunteers. METHODS AND RESULTS: Amlodipine (5 mg) or S (-) amlodipine (2.5 mg) was administered to 27 normal human volunteers. Whole-blood viscosity (WBV) at different shear rates, plasma viscosity (PV), red cell rigidity (RCR), red cell aggregation (RCA), hematocrit (Hct), plasma hemoglobin, along with plasma drug concentration were determined at time intervals, t = 0, 4, 8, 12, and 24 h. Statistically significant reductions were observed at tmax = 4 h in WBV at shear rates of 0.512 s-1 (p < 0.005), WBV at shear rates of 5.26 s-1 (p < 0.01), PV (p < 0.05), and Hct (p < 0.01). At t = 8 h, as drug concentration reduced, some of the changes persisted and later slowly decreased with the decreasing drug concentration till t = 24 h. Red blood cell-related parameters such as RCA and RCR remained unaltered. WBV values at all shear rates, when corrected for Hct = 0.45, did not show deviation from their original values at any time. CONCLUSIONS: Amlodipine causes a reduction in Hct and blood viscosity, along with hemodilution. These effects persist as long as the drug remains in plasma. Edema resulting from chronic dosing may be explained by the aforementioned effects. It is possible that antihypertensive action of the drug may be due to a combination of vasodilatation and an improvement in the HR properties.


Asunto(s)
Amlodipino/administración & dosificación , Viscosidad Sanguínea/efectos de los fármacos , Edema/sangre , Agregación Eritrocitaria/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/administración & dosificación , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Edema/etiología , Voluntarios Sanos , Hematócrito , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Masculino , Método Simple Ciego , Resultado del Tratamiento , Adulto Joven
18.
Am J Cardiovasc Drugs ; 19(3): 313-323, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30919249

RESUMEN

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).


Asunto(s)
Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Perindopril/administración & dosificación , Anciano , Amlodipino/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Perindopril/efectos adversos , Índice de Severidad de la Enfermedad
19.
J Renin Angiotensin Aldosterone Syst ; 20(1): 1470320319839525, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30915878

RESUMEN

OBJECTIVE:: In our recent study, non-Gaussianity of heart rate variability (λ25s), an indicator of sympathetic nerve activity, did not change during two-day treatment with the angiotensin II type 1 receptor blocker (ARB) azilsartan. Coadministration of calcium channel blockers (CCBs) might affect the study results. METHODS:: In this subanalysis, 20 patients with chronic kidney disease (14 men; age 61±15 years) were divided into three groups: patients with coadministration of L-type CCB, patients without coadministration of CCB, and patients with coadministration of sympathoinhibitory (L/T- or L/T/N-type) CCB. λ25s was calculated separately in daytime and nighttime. RESULTS:: Daytime λ25s at baseline was higher in patients with L-type CCB coadministration (0.62±0.18, n = 5) compared with those without CCB (0.49±0.13, n = 11) and those with sympathoinhibitory CCB (0.46±0.06, n = 4). The relationship between the changes in daytime λ25s and systolic blood pressure was positive in patients with L-type CCB coadministration, whereas the relationship was inverse in the other two groups. A larger decrease in daytime λ25s was shown in patients with L-type CCB coadministration compared with those in the other two groups. CONCLUSIONS:: CCBs, as well as diuretics, are recommended as second-line antihypertensive agents. Our results suggested that ARBs can overwhelm the activation of sympathetic nerve activity stimulated by coadministration of L-type CCBs.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bencimidazoles/administración & dosificación , Bencimidazoles/farmacología , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/farmacología , Oxadiazoles/administración & dosificación , Oxadiazoles/farmacología , Sistema Nervioso Simpático/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad
20.
Eur J Pharm Biopharm ; 139: 142-152, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30902733

RESUMEN

Nifedipine and nicardipine loaded PLGA extrudates have a great potential to prevent cerebral vasospasms after subarachnoid hemorrhage or surgical clipping of aneurysm. A constant release over approx. two weeks is desired. Although in vivo studies on humans have been reported, there is limited knowledge about the release kinetics and the underlying mechanisms. Therefore, nifedipine and nicardipine loaded PLGA implants with different drug loads were manufactured by extrusion and investigated. In addition to the measurements of the release kinetics, GPC, DSC, X-ray diffraction and light microscopic investigations were performed for a detailed characterization. The water uptake and polymer erosion studies showed an initial lag phase of 5-7 days and an acceleration of both processes thereafter. With 5% loaded implants a higher drug release compared to 10% drug loaded polymers could be achieved and not only the relative amount of drug release (% of loaded drug), but surprisingly also the absolute amount of the released drug increased. The drugs were initially in an amorphous state. For nifedipine, formation of drug crystals with time has been observed by light microscopy and X-ray diffraction. The analysis of the drug content in the degrading polymer showed a very large increase from 10% to about 20% (nifedipine) and over 50% (nicardipine). In contrast, no or only a moderate increase of the drug content occurred for initially 5% loaded polymer implants. We postulate that water penetration and polymer degradation induced changes of the microenvironment lead to supersaturated systems. A supersaturated state is faster reached for polymers with higher drug load and therefore, drug precipitation takes place at earlier time points. As a result, drug release might be incomplete for poorly soluble drugs and paradoxically, the total amount of drug release might be higher for systems with a lower drug load. Drug release is initially controlled by the PLGA matrix, but later by the dissolution kinetics of the precipitated drug which are very slow for poorly soluble drugs according to the Noyes-Whitney equation.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacocinética , Portadores de Fármacos/química , Implantes de Medicamentos/farmacocinética , Liberación de Fármacos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Plásticos Biodegradables/química , Bloqueadores de los Canales de Calcio/administración & dosificación , Rastreo Diferencial de Calorimetría , Composición de Medicamentos/métodos , Implantes de Medicamentos/administración & dosificación , Humanos , Nicardipino/administración & dosificación , Nicardipino/farmacocinética , Nifedipino/administración & dosificación , Nifedipino/farmacocinética , Solubilidad , Difracción de Rayos X
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