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1.
Endocrinology ; 163(8)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35695766

RESUMO

Regulatory mechanisms of iodothyronine deiodinases (DIOs) require further elucidation, and conventional methods for evaluating DIOs are unsuitable for high-throughput screening (HTS). Here we explored factors of transcriptional regulation of 3 types of DIOs (DIO1, DIO2, and DIO3) from a chemical library using our designed HTS. We constructed HTS based on a promoter assay and performed a screen of 2480 bioactive compounds. For compounds that were clinically approved, we validated hit compounds through a retrospective cohort study in our department that evaluated changes in thyroid function in patients using the compounds as drug therapy. Furthermore, we verified the involvement of DIOs using mice treated with the compounds. Of the hit compounds, 6 and 7 compounds transcriptionally up- and downregulated DIO1, respectively; 34 transcriptionally upregulated DIO2; and 5 and 2 compounds transcriptionally up- and downregulated DIO3, respectively. The cohort study clarified the clinical effects of some hit compounds: ritodrine increased free triiodothyronine (fT3)/free thyroxine (fT4) ratio and decreased serum thyroid-stimulating hormone (TSH) levels, tadalafil increased serum fT3 levels, and tyrosine kinase inhibitors (TKIs) decreased serum fT3 and fT4 levels and increased serum TSH levels. Following in vivo experiments using treated mice, consistent results were observed in ritodrine, which upregulated DIO2 in the thyroid gland. In conclusion, we completed HTS for DIOs and obtained attractive hit compounds. Our cohort study revealed the clinical significance of ritodrine, sildenafil, and TKIs. We hope our unique method will contribute to analyzing various targets and lists of hit compounds will promote understanding of DIOs.


Assuntos
Iodeto Peroxidase , Ritodrina , Animais , Estudos de Coortes , Ensaios de Triagem em Larga Escala , Humanos , Iodeto Peroxidase/genética , Camundongos , Estudos Retrospectivos , Tireotropina , Tiroxina , Tri-Iodotironina
2.
PLoS One ; 17(3): e0265872, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35358222

RESUMO

Ritodrine hydrochloride is used for pregnancy prolongation and intrauterine fetal resuscitation. However, its clinical significance in intraamniotic inflammation during preterm labor and intrauterine fetal distress is unclear. We investigated the effects of maternal ritodrine hydrochloride administration (MRA; 200 µg/min for 2 h, followed by 800 µg/min for 2 h after 24 h) on fetal physiological parameters. For this purpose, we used chronically instrumented pregnant sheep at 113-119 d (term = 145 d) of gestation without (Group 1, n = 5) and with (Group 2, n = 5) intraamniotic inflammation induced by lipopolysaccharide injection into the amniotic cavity. The changes in fetal heart rate (FHR) and short-term variability (STV) and long-term variability (LTV) in FHR, fetal blood pressure, and fetal arterial blood gas (FABG) values were measured before and at 1 and 2 h after initiating MRA. Before MRA, all parameters were similar between Groups 1 and 2; however, there was significantly higher STV in Group 2 than in Group 1 before MRA at 800 µg/min, significantly higher partial arterial pressure of carbon dioxide in FABG in Group 2 than in Group 1 before MRA at 200 µg/min, and significantly lower blood glucose (BG) in Group 2 than in Group 1 before MRA at 800 µg/min. One hour after MRA, the FHR, STV, and LTV were significantly higher at 800 µg/min than those at the baseline in Group 1, as determined by the Friedman test; however, no significant difference was observed in Group 2. Additionally, the FABG pH significantly decreased 1 h after MRA at 800 µg/min in Group 2, whereas FABG lactate and BG significantly increased 2 h after MRA at 800 µg/min in Groups 1 and 2. Thus, short-term MRA at 800 µg/min increased the FHR, STV, and LTV significantly; these values were further modified under intraamniotic inflammation.


Assuntos
Ritodrina , Animais , Gasometria , Feminino , Feto , Frequência Cardíaca , Frequência Cardíaca Fetal , Inflamação , Gravidez , Ovinos
3.
Minerva Obstet Gynecol ; 74(4): 337-342, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35107244

RESUMO

BACKGROUND: Treatment with beta-agonist tocolytics preceding external cephalic version (ECV) attempt increases success rates. Most studies have focused on intravenously and orally administered beta-agonists, while other administration routes including intramuscularly (IM) and subcutaneously (SC) are understudied. The aim of this study was to compare the efficacy of IM ritodrine to SC salbutamol given prior to ECV. METHODS: A retrospective study of patients who underwent ECV between 1/2012 and 12/2019 at two medical centers. We compared patients undergoing ECV following IM ritodrine versus SC salbutamol. We matched the two groups by parity and placental location. Maternal, pregnancy, ECV procedure and neonatal characteristics were compared. RESULTS: Overall, 601 women were included in each group. Median maternal age and amniotic fluid index (AFI) were lower in the Ritodrine group (27 vs. 32 years, P<0.001, 11 vs. 15 AFI cm, P<0.001, respectively). The median gestational age at ECV was higher in the Ritodrine group (380/7 vs. 370/7 weeks gestation). Success rate was higher in the Ritodrine group (71.7% vs. 63.8%, P=0.003). Vaginal delivery rate was higher in the Ritodrine group (70.7% vs. 60.1%, P<0.001). The number needed to treat to benefit was 10. In a multivariate analysis, Ritodrine was independently associated with higher ECV success rates as compared with Salbutamol (aOR 2.1, 95%CI 1.52-2.89). CONCLUSIONS: Intramuscular ritodrine significantly improved the success rate of ECV compared to SC salbutamol, and both drugs were safe and acceptable before ECV.


Assuntos
Apresentação Pélvica , Ritodrina , Versão Fetal , Albuterol/uso terapêutico , Apresentação Pélvica/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Placenta , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Ritodrina/uso terapêutico , Versão Fetal/métodos
4.
J Matern Fetal Neonatal Med ; 35(1): 80-85, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931641

RESUMO

OBJECTIVE: To assess the efficacy of atosiban versus ritodrine as tocolytics in external cephalic version (ECV). MATERIALS AND METHODS: A prospective comparative trial was carried out in a tertiary hospital. 430 women with singleton breech pregnancies ≥36 weeks were recruited for ECV, 215 with ritodrine and 215 with atosiban as tocolytic agents. The efficacy, complications and perinatal outcomes were compared between both groups. The associations between variables were analyzed using the chi-square test (χ2) (qualitative), Student's t test (quantitative, parametric) or Mann-Whitney test (nonparametric). Statistical significance was established as p < .05. RESULTS: The overall ECV success rate was 47.9% (206/430), 46.0% in the atosiban group (99/215) and 49.8% in the ritodrine group (107/215). This difference showed no statistical significance (p = .440). A higher rate of uterine contractions after the maneuver was observed in the atosiban group (34.4 versus 22.8%; p = .008), but without clinical relevance. Perinatal outcomes were similar in both groups, with no significant differences. CONCLUSION: Atosiban and ritodrine showed similar efficacy as tocolytic agents in ECV, with no differences in complications and perinatal outcomes between these two agents.


Assuntos
Apresentação Pélvica , Ritodrina , Tocolíticos , Versão Fetal , Feminino , Humanos , Gravidez , Estudos Prospectivos , Vasotocina/análogos & derivados
5.
BMC Pediatr ; 21(1): 370, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465290

RESUMO

BACKGROUND: Betamimetics have been used for tocolysis extensively in the past, and one of them, ritodrine is widely used in Japan. Various adverse events have been reported for this agent, including newborn hypoglycemia and hypokalemia, as well as maternal hypokalemia and rebound hyperkalemia; however, cases of neonatal rebound hyperkalemia are not described in the literature. CASE PRESENTATION: A male infant born at 36 weeks of gestation by cesarean section at a local maternity clinic suddenly entered cardiopulmonary arrest with ventricular tachycardia and fibrillation due to hyperkalemia (K+, 8.7 mmol/L). No monitoring, examination of blood electrolyte levels, or infusions had been performed prior to this event. Maternal infusion of ritodrine (maximum dose, 170 µg/min) had been performed for 7 weeks prior to cesarean section. After resuscitation combined with calcium gluconate, the infant died at 4 months old due to serious respiratory failure accompanied by acute lung injury following shock. No cause of hyperkalemia other than rebound hyperkalemia associated with ritodrine was identified. CONCLUSIONS: This case report serves as a warning regarding the potential risk of neonatal rebound hyperkalemia in association with maternal long-term ritodrine administration.


Assuntos
Hiperpotassemia , Trabalho de Parto Prematuro , Ritodrina , Tocolíticos , Cesárea , Feminino , Humanos , Hiperpotassemia/induzido quimicamente , Lactente , Recém-Nascido , Masculino , Gravidez , Ritodrina/efeitos adversos , Tocolíticos/efeitos adversos
6.
Pediatr Allergy Immunol ; 32(7): 1455-1463, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34013624

RESUMO

BACKGROUND: The effects of maternal ritodrine hydrochloride administration (MRA) during pregnancy on fetuses and offspring are not entirely clear. The present study aimed to evaluate the association between MRA and childhood wheezing using data from a nationwide Japanese birth cohort study. METHODS: This study analyzed the data of the participants enrolled in the Japan Environment and Children's Study, a nationwide prospective birth cohort study, between 2011 and 2014. Data of women with singleton live births after 22 weeks of gestation were analyzed. The participants were divided according to MRA status. Considering childhood factors affecting the incidence of wheezing, including smoking environment and childhood viral infections, a logistic regression model was used to calculate odds ratios for "wheezing ever," diagnosis of asthma in the last 12 months, and "asthma ever" in women with MRA, with women who did not receive MRA as the reference. Additionally, participants were stratified by term births, and odds ratios for outcomes were calculated using a logistic regression model. RESULTS: A total of 68,123 participants were analyzed. The adjusted odds ratio for wheezing was 1.17 (95% confidence interval, 1.12-1.22). The adjusted odds ratios for the other outcomes did not significantly increase after adjusting for childhood factors. The same tendency was confirmed after excluding women with preterm births. CONCLUSION: MRA was associated with a slightly increased incidence of childhood wheezing up to three years, irrespective of term or preterm birth status. It is important that perinatal physicians consider the potential effects of MRA on the offspring's childhood health.


Assuntos
Nascimento Prematuro , Ritodrina , Criança , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Japão/epidemiologia , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Sons Respiratórios , Ritodrina/efeitos adversos
7.
Kobe J Med Sci ; 66(5): E166-E169, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-34001683

RESUMO

OBJECTIVE: Acute pulmonary edema associated with ritodrine hydrochloride is a rare, life-threatening complication, and dose and duration of ritodrine use are closely associated with this pathology. We report a case of acute pulmonary edema associated with short-duration infusion of ritodrine hydrochloride in a patient with pectus excavatum as an underlying factor. CASE REPORT: A 30-year-old healthy pregnant woman was treated with oral ritodrine for tocolysis between 31 and 35 weeks of pregnancy. At 36 weeks of gestation, she went into preterm labor, with premature rupture of the membrane and breech presentation, and received an infusion of ritodrine hydrochloride for a few hours. Although she was normotensive until labor onset, mild hypertension and proteinuria were recognized. Intraoperatively, a funnel-chest deformity was observed, and she developed postoperative pulmonary edema associated with dyspnea and wet cough and confirmed on chest radiography and arterial gas analysis, and recovered with supportive care. CONCLUSION: Small-dose infusion of ritodrine hydrochloride might cause pulmonary edema in patients with underlying medical problems, including pectus excavatum.


Assuntos
Pulmão/efeitos dos fármacos , Trabalho de Parto Prematuro/prevenção & controle , Edema Pulmonar/induzido quimicamente , Ritodrina/administração & dosagem , Tocolíticos/administração & dosagem , Contração Uterina/efeitos dos fármacos , Adulto , Cesárea , Feminino , Humanos , Infusões Parenterais , Gravidez , Edema Pulmonar/tratamento farmacológico , Ritodrina/efeitos adversos , Ritodrina/uso terapêutico , Tocolíticos/efeitos adversos , Tocolíticos/uso terapêutico , Resultado do Tratamento
8.
Med Sci Monit ; 27: e929743, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33731666

RESUMO

BACKGROUND Premature labor is an important cause of infant death and long-term disability. This study aimed to explore the safety and effectiveness of combining the tocolytic agents atosiban and ritodrine to extend gestation. MATERIAL AND METHODS The study included 52 patients with late threatened abortion and threatened premature labor between 20°â¸7 and 336⸍7 weeks' gestation who were administrated continuous tocolytic agents for 48 h. Patients were divided into a research group receiving ritodrine combined with atosiban, owing to having no response to ritodrine alone (n=30), and a control group receiving ritodrine alone (n=22). The mean infusion rate and duration of tocolytic administration, gestation extension, pregnancy outcomes, and adverse effects were recorded. Routine blood tests, including C-reactive protein, and cultures for leukorrhea, candida, and mycoplasma were performed before and 1 week after treatment. RESULTS Patients receiving ritodrine with atosiban had a mean gestation extension of 42.53±31.70 days. The extension of gestation of the research group was statistically shorter than that of the control group (P<0.05). The fetal loss rate, newborn birth weight, and Apgar score at 1 min were similar between the 2 groups (all, P>0.05). The research group had a lower incidence of palpitations than the control group (P<0.05). CONCLUSIONS For patients with late threatened abortion or threatened premature labor not controlled with ritodrine alone, ritodrine combined with atosiban extends gestation and improves pregnancy outcomes. For patients with abnormal uterine contractions, routine testing for reproductive tract infection should be performed. When infection is present, anti-infective therapy should be administered.


Assuntos
Ameaça de Aborto/tratamento farmacológico , Trabalho de Parto Prematuro/tratamento farmacológico , Ritodrina/uso terapêutico , Vasotocina/análogos & derivados , Ameaça de Aborto/prevenção & controle , Adulto , Quimioterapia Combinada/métodos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Trabalho de Parto Prematuro/prevenção & controle , Gravidez , Resultado da Gravidez , Ritodrina/metabolismo , Tocolíticos/efeitos adversos , Tocolíticos/uso terapêutico , Vasotocina/metabolismo , Vasotocina/uso terapêutico
9.
J Med Case Rep ; 15(1): 126, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33743806

RESUMO

BACKGROUND: We report a case of pulmonary edema induced by tocolytic agents that was successfully managed with noninvasive positive-pressure ventilation (NPPV) and resulted in extended gestation. CASE PRESENTATION: A 36-year-old Japanese pregnant woman received tocolytic therapy with ritodrine hydrochloride, magnesium sulfate, nifedipine, and betamethasone from 28 weeks of gestation. She developed respiratory failure. and her chest X-ray showed enlarged pulmonary vascular shadows. At 29 weeks and 1 day of gestation, she was diagnosed with pulmonary edema induced by tocolytic agents. Because respiratory failure worsened 2 days after ritodrine hydrochloride and magnesium sulfate were stopped, NPPV was initiated. Her respiratory status improved and she was weaned off of NPPV after 3 days. She underwent cesarean section because of breech presentation at 30 weeks and 0 days of gestation due to initiation of labor pains. CONCLUSIONS: NPPV can be safely administered in cases of tocolytic agent-induced pulmonary edema during pregnancy.


Assuntos
Edema Pulmonar , Ritodrina , Tocolíticos , Adulto , Cesárea , Feminino , Humanos , Respiração com Pressão Positiva , Gravidez , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/terapia , Ritodrina/efeitos adversos , Tocolíticos/efeitos adversos
10.
Drug Discov Ther ; 15(1): 14-19, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33642492

RESUMO

Prematurely born infants face unique risks, and the treatment of imminent preterm birth is thus an important part of perinatal care. Ritodrine hydrochloride (Rito) is widely used as a therapeutic agent to treat imminent preterm birth in Japan. Following assessment of the risks and benefits of short-acting ß-agonists, including Rito, in Europe, however, the use of Rito has begun to be questioned. Thus, in this study we investigated the safety of Rito in the treatment of imminent preterm birth, with a particular focus on the adverse effects (AEs) on fetuses and newborn infants. Using the Pharmaceuticals and Medical Devices Agency of Japan's Japanese Adverse Drug Event Report (JADER) database, the AEs on fetuses and newborns caused by oral and injected Rito were extracted and analyzed. The reported odds ratios for oral Rito were significantly higher for fetal tachycardia, fetal bradycardia, neonatal hypoglycemia, and neonatal heart failure than for other drugs. The reported odds ratios for Rito injection were significantly higher for fetal tachycardia and neonatal hypoglycemia than for other drugs. Oral drugs had more adverse effect reports than injectable drugs.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Nascimento Prematuro/prevenção & controle , Ritodrina/administração & dosagem , Tocolíticos/administração & dosagem , Administração Oral , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Feminino , Humanos , Recém-Nascido , Injeções Intramusculares , Japão , Gravidez , Ritodrina/efeitos adversos , Tocolíticos/efeitos adversos , Adulto Jovem
11.
Sci Rep ; 11(1): 1146, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441922

RESUMO

Beta-2 adrenergic receptor (B2AR) agonists, used as asthma treatments and tocolytics during pregnancy, have recently been reported to be associated with autism in their offspring. However, the particular link between autism and ritodrine, a common type of B2AR agonist used solely as tocolytics, has never been substantiated with any nationwide database. Thus, we aimed to examine the association between in utero exposure of ritodrine and the risk of autism in their offspring using a national database. This population-based cohort study was conducted by merging the Korea National Health Insurance claims database and National Health Screening Program for Infants and Children database. These databases included all women who had delivered singleton between January 2007 and December 2008 in Korea. Out of the total 770,016 mothers, 30,959 (4.02%) were exposed to ritodrine during pregnancy, and 5583 (0.73%) of their children were identified as having autism, defined until 8 years of age. According to our analysis, the overall cumulative incidence of autism up to 8 years was 1.37% in ritodrine exposure group and 0.70% in ritodrine non-exposure group (p < 0.05, log-rank test). By Cox proportional hazard analysis, use of ritodrine in preterm birth was associated with significantly higher hazard of autism [adjusted hazard ratio: 1.23, 95% CI 1.04-1.47], after adjusting for confounding variables including maternal age, parity, cesarean section, preterm labor, steroid use, birth weight, gender, and preeclampsia. Thus, in utero exposure to ritodrine was associated with an increased risk of autism in their offspring.


Assuntos
Transtorno Autístico/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ritodrina/efeitos adversos , Tocolíticos/efeitos adversos , Adulto , Transtorno Autístico/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Gravidez , Nascimento Prematuro/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , República da Coreia/epidemiologia
12.
J Matern Fetal Neonatal Med ; 34(18): 3008-3013, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31608725

RESUMO

OBJECTIVE: Published series regarding interventions for facilitating external cephalic version (ECV) have concluded that parenterally administered beta-stimulant tocolytics, increased ECV success rate and reduced the number of cesarean sections. However, there were insufficient data regarding calcium channel blockers to provide good evidence regarding its efficacy. Given the paucity of literature, we aimed to compare the efficacy of nifedipine to that of ritodrine on ECV success rates. METHODS: This is a retrospective case control study of prospectively collected data of patients who underwent ECV between January 2012 and December 2013 at Bikur Cholim Medical Center and Hadassah-Hebrew University Medical Center in Jerusalem, Israel. Patient undergoing ECV with tocolysis by ritodrine were compared with those using nifedipine as tocolysis. Patients were matched in a one-to-one ration by parity and placental location. RESULTS: Overall, 148 women received ritodrine and 148 women received nifedipine before ECV procedure. Overall success rate was higher among the ritodrine group (82.4 vs. 63.5%, p < .001). Among nulliparous and among parous, success rate was higher in the ritodrine group (78.9 vs. 57.9 and 88.6 vs. 73.5%, p = .001, p = .04, respectively). Vaginal delivery rate was higher among the ritodrine group (86.5 vs. 68.9%, p < .001). Cesarean delivery rate was 31.1% for the nifedipine group versus 13.5% in the ritodrine group (p < .001). Number needed to treat to benefit (NNTb) 5.7 (95% confidence interval 3.7-12.1). Overall, 216 of 296 (72.9%) of ECV were successful. Ritodrine was associated with higher success rates as compared with nifedipine (56.5 vs. 32.5%, p < .001). In a multivariate analysis, ritodrine tocolytic therapy was independently associated higher ECV success rates as compared to nifedipine (OR 4.54, 95% CI 2.38-9.09). Higher amniotic fluid index (OR 1.16, 95% CI 1.05-1.28) and nulliparity (OR 0.16, 95% CI 0.08-0.30) were additional independent predictors of ECV outcome. CONCLUSION: Ritodrine significantly improve the success of ECV compared with nifedipine. Both drugs are shown to be safe.


Assuntos
Apresentação Pélvica , Ritodrina , Versão Fetal , Estudos de Casos e Controles , Feminino , Humanos , Israel , Nifedipino , Placenta , Gravidez , Estudos Retrospectivos
13.
PLoS One ; 15(11): e0241215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33166306

RESUMO

INTRODUCTION: Ritodrine is one of the most commonly used tocolytics in preterm labor, acting as a ß2-adrenergic agonist that reduces intracellular calcium levels and prevents myometrial activation. Ritodrine infusion can result in serious maternal complications, and pulmonary edema is a particular concern among these. The cause of pulmonary edema following ritodrine treatment is multifactorial; however, the contributing genetic factors remain poorly understood. This study investigates the genetic variants associated with ritodrine-induced pulmonary edema. METHODS: In this case-control study, 16 patients who developed pulmonary edema during ritodrine infusion [case], and 16 pregnant women who were treated with ritodrine and did not develop pulmonary edema [control] were included. The control pregnant women were selected after matching for plurality and gestational age at the time of tocolytic use. Maternal blood was collected during admission for tocolytic treatment, and whole exome sequencing was performed with the stored blood samples. RESULTS: Gene-wise variant burden (GVB) analysis resulted in a total of 71 candidate genes by comparing the cumulative effects of multiple coding variants for 19729 protein-coding genes between the patients with pulmonary edema and the matched controls. Subsequent data analysis selected only the statistically significant and deleterious variants compatible with ritodrine-induced pulmonary edema. Two final candidate variants in CPT2 and ADRA1A were confirmed by Sanger sequencing. CONCLUSIONS: We identified new potential variants in genes that play a role in cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) regulation, which supports their putative involvement in the predisposition to ritodrine-induced pulmonary edema in pregnant women.


Assuntos
Variação Genética/genética , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/genética , Ritodrina/efeitos adversos , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Miométrio/efeitos dos fármacos , Trabalho de Parto Prematuro/tratamento farmacológico , Trabalho de Parto Prematuro/genética , Gravidez , Tocolíticos/efeitos adversos
14.
Obstet Gynecol Clin North Am ; 47(4): 569-586, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33121645

RESUMO

"Trials evaluating tocolytic use in preterm premature rupture of membranes (PPROM) have been small and lacked adequate power to evaluate uncommon outcomes. There still is much controversy on the benefit, length of use, route, and drug of choice among clinicians treating patients with PPROM. Most professional medical societies would propose to consider the use of tocolytics for 48 hours to allow for corticosteroid administration or to allow for maternal transfer to a higher level of care. Longer treatment regimens may lead to adverse maternal and perinatal outcomes. Insufficient data are available to make stronger and more definitive recommendations."


Assuntos
Ruptura Prematura de Membranas Fetais/tratamento farmacológico , Tocolíticos/uso terapêutico , Corticosteroides/uso terapêutico , Feminino , Humanos , Recém-Nascido , Sulfato de Magnésio/uso terapêutico , Gravidez , Nascimento Prematuro/prevenção & controle , Ritodrina/uso terapêutico , Tocólise/métodos
15.
Biosci. j. (Online) ; 36(4): 1491-1497, 01-06-2020. tab
Artigo em Inglês | LILACS | ID: biblio-1147326

RESUMO

This project was designedto explore the effects of ritodrine hydrochloride combined with magnesium sulfate in the prevention of preterm delivery of patients with threatened premature birth. 128 cases of threatened premature birth were randomly divided into two groups according to the number table method. The control group was treated with magnesium sulfate, while the study group was treated with ritodrine hydrochloride combined with magnesium sulfate. The data (p > 0.05) was analyzed using SPSS 18.0 and was subjected to Chi-square and t-test. The onset time and prolonged gestation time of the study group were shorter than those of the control group (p < 0.05). There was no difference in the incidence of myocardial ischemia between the study group and the control group (p > 0.05). The heart rate per minute of the study group was higher than that of the control group (p < 0.05). There was no difference in blood pressure between the study group and the control group. Nevertheless, the neurological function, pregnancy outcome, and neonatal status of the group were better than those of the control group (p < 0.05).(AU)


Este projeto foi desenvolvido para explorar os efeitos do cloridrato de ritodrina combinado com sulfato de magnésio na prevenção do parto prematuro de pacientes com risco de nascimento prematuro. 128 casos de nascimento prematuro ameaçado foram divididos aleatoriamente em dois grupos, de acordo com o método da tabela numérica. O grupo de controle foi tratado com sulfato de magnésio, enquanto o grupo de estudo foi tratado com cloridrato de ritodrina combinado com sulfato de magnésio. Os dados (p > 0,05) foram analisados pelo SPSS 18.0 e submetidos ao teste do qui-quadrado e ao teste t. O tempo de início e o tempo prolongado de gestação do grupo de estudo foram menores que os do grupo de controle (p < 0,05). Não houve diferença na incidência de isquemia miocárdica entre o grupo de estudo e o grupo de controle (p > 0,05). A frequência cardíaca por minuto do grupo de estudo foi superior à do grupo controle (p < 0,05). Não houve diferença na pressão arterial entre o grupo de estudo e o grupo de controle. No entanto, a função neurológica, o resultado da gravidez e o status neonatal do grupo foram melhores do que os do grupo de controle (p < 0,05).(AU)


Assuntos
Ritodrina , Trabalho de Parto Prematuro , Sulfato de Magnésio , Pressão Sanguínea , Gravidez , Resultado da Gravidez , Isquemia Miocárdica , Nascimento Prematuro , Prevenção de Doenças , Pressão Arterial , Frequência Cardíaca
16.
Pharmacogenet Genomics ; 30(6): 124-130, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32371615

RESUMO

OBJECTIVE: The present prospective follow-up study aimed to evaluate the effects of KCNMB2 gene polymorphisms on ritodrine efficacy and adverse drug events (ADEs) in patients with preterm labor. METHODS: A total of 163 preterm labor patients were included in this single-center study. Nine single nucleotide polymorphisms (SNPs) in the KCNMB2 gene (rs10936979, rs7624046, rs7429015, rs7625907, rs6443559, rs9839376, rs9637454, rs11918114, and rs1382045) were assessed. The primary endpoint was time to delivery, and the secondary endpoint was ritodrine-induced ADEs. RESULTS: Patients with variant homozygotes of two SNPs (rs7624046 and rs9839376), which were in linkage disequilibrium, showed 2.06 [95% confidence interval (CI), 1.14-3.73] and 2.68 (95% CI, 1.16-6.20) times the hazard of time to delivery compared to wild-type allele carriers, respectively. Among demographic characteristics, gestational age at start of drug therapy and modified Bishop score were significant factors for time to delivery. Regarding safety outcomes, patients with variant homozygotes of rs7625907 had fewer ADEs compared to those with other genotypes (odds ratio, 0.32; 95% CI, 0.13-0.83). CONCLUSION: This pharmacogenomic study suggests that ritodrine efficacy and ADEs are associated with KCNMB2 gene polymorphisms in patients with preterm labor.


Assuntos
Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Trabalho de Parto Prematuro/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Ritodrina/administração & dosagem , Tocolíticos/administração & dosagem , Adulto , Feminino , Idade Gestacional , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Idade Materna , Trabalho de Parto Prematuro/genética , Gravidez , Segundo Trimestre da Gravidez/genética , Terceiro Trimestre da Gravidez/genética , Estudos Prospectivos , Ritodrina/efeitos adversos , Tocolíticos/efeitos adversos
17.
Sci Rep ; 10(1): 7804, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385354

RESUMO

Our aim was to evaluate the association between ritodrine and magnesium sulfate (MgSO4) and the occurrence of neonatal hyperkalemia or hypoglycemia among late preterm infants in a retrospective cohort study. We used a nationwide obstetrical database from 2014. A total of 4,622 live preterm infants born at 32-36 gestational weeks participated. Fourteen risk factors based on both clinical relevance and univariate analysis were adjusted in multivariable logistic regression analyses. Neonatal hyperkalemia and hypoglycemia occurred in 7.6% (284/3,732) and 32.4% (1,458/4,501), respectively. Occurrence of hyperkalemia was associated with concomitant usage of ritodrine and MgSO4 compared with no usage (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.09-2.15). Occurrence of hypoglycemia was associated with ritodrine alone (aOR 2.58 [CI 2.21-3.01]) and with concomitant usage of ritodrine and MgSO4 (aOR 2.59 [CI 2.13-3.15]), compared with no usage, and was associated with long-term usage (≥ 48 hours) of ritodrine and cessation directly before delivery. In conclusion, in late preterm infants, usage of ritodrine together with MgSO4 was associated with occurrence of critical neonatal hyperkalemia, and long-term usage of ritodrine and cessation directly before delivery were associated with neonatal hypoglycemia.


Assuntos
Hiperpotassemia/epidemiologia , Hipoglicemia/epidemiologia , Sulfato de Magnésio/efeitos adversos , Ritodrina/efeitos adversos , Adulto , Sinergismo Farmacológico , Feminino , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/patologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/patologia , Lactente , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Recém-Nascido/patologia , Recém-Nascido Prematuro , Japão/epidemiologia , Sulfato de Magnésio/uso terapêutico , Trabalho de Parto Prematuro/tratamento farmacológico , Trabalho de Parto Prematuro/patologia , Gravidez , Fatores de Risco , Ritodrina/uso terapêutico
18.
Sci Rep ; 10(1): 1351, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992805

RESUMO

The present prospective follow-up study aimed to evaluate the effects of GRK5 polymorphisms on ritodrine efficacy and adverse drug events (ADEs) in pregnant women undergoing preterm labor. A total of 162 women undergoing preterm labor were included in the study. Seven single nucleotide polymorphisms (SNPs) in the GRK5 gene (rs915120, rs2230345, rs2230349, rs7923896, rs1020672, rs4752308, and rs4752292) were assessed. Homozygous variant carriers of rs4752292 and rs1020672 had 0.6 times the hazard of delivery compared to wild-type allele carriers (95% confidence interval [CI], 0.41~0.99 and 0.38~0.99, respectively). In addition, homozygous variant carriers of rs4752292 and rs1020672 had 2.4-fold more (95% CI, 1.10~4.98) and 2.3-fold more (95% CI, 1.04~5.06) ADEs compared to those with the wild-type homozygotes, respectively. Among demographic variables, gestational age and modified Bishop score were significant factors associated with time to delivery, while body weight and maximum ritodrine infusion rate were significant factors associated with ADEs. In silico analysis showed that both rs4752292 and rs1020672 had the potential to affect mRNA splicing by alteration of splicing motifs. The present study shows that ritodrine efficacy and ADEs are associated with GRK5 gene polymorphisms in pregnant women undergoing preterm labor.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Quinase 5 de Receptor Acoplado a Proteína G/genética , Polimorfismo Genético , Ritodrina/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Adulto , Alelos , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Nascimento Prematuro , Modelos de Riscos Proporcionais , Curva ROC , Ritodrina/administração & dosagem , Ritodrina/farmacologia
19.
Res Vet Sci ; 128: 43-48, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31710963

RESUMO

ß2-adrenoceptor agonists are considered the most effective drugs to counteract bronchoconstriction in horses with asthma, but only clenbuterol is commonly employed in clinical practice. We evaluated the effects of different selective ß2 agonists: clenbuterol, ritodrine, salbutamol, and fenoterol on the contractions of isolated bronchial muscle of horses induced by electrical field stimulation (EFS), carbachol, histamine, and KCl. All ß2 agonists reduced the amplitude of contraction induced by the different stimuli but with variable efficacy and potency. Fenoterol and salbutamol were more effective than clenbuterol in relaxing the bronchial contractions induced by EFS and histamine, and were able to completely abolish carbachol-induced contractions, unlike clenbuterol and ritodrine. The respective potency values (pEC50) of clenbuterol, ritodrine, salbutamol, and fenoterol were 7.74 ±â€¯0.20, 7.77 ±â€¯0.17, 7.30 ±â€¯0.23, 8.01 ±â€¯0.13, for EFS-induced contractions; 8.39 ±â€¯0.26, 5.49 ±â€¯0.28, 6.63 ±â€¯0.14, 7.68 ±â€¯0.11, for carbachol-induced contraction; 7.39 ±â€¯0.27, 7.04 ±â€¯0.28, 6.45 ±â€¯0.34, 7.34 ±â€¯0.22, for histamine-induced contraction; 7.15 ±â€¯0.06, 6.07 ±â€¯0.20, 6.48 ±â€¯0.14, 6.70 ±â€¯0.18, for KCl-induced contraction. Salbutamol and fenoterol showed a higher efficacy than clenbuterol in relaxing horse bronchial muscle pre-contracted by most stimuli. Clenbuterol displayed a good potency but a rather low efficacy, and this may be due to its partial agonist nature; ritodrine showed lower or not significantly different efficacy and potency compared to the other agonists. An evaluation of the clinical efficacy by fenoterol and salbutamol in horses with asthma could be of great interest to assess if they could represent more effective bronchodilators compared to clenbuterol.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Brônquios/efeitos dos fármacos , Broncodilatadores/farmacologia , Cavalos/fisiologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Albuterol/farmacologia , Animais , Brônquios/fisiologia , Clembuterol/farmacologia , Fenoterol/farmacologia , Masculino , Contração Muscular/fisiologia , Músculo Liso/fisiologia , Ritodrina/farmacologia
20.
J Perinat Med ; 47(7): 717-723, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31369397

RESUMO

Background We aimed to analyze the success rate of external cephalic version (ECV) for breech presentations performed in our center between March 2011 and March 2016. We evaluated factors related to a successful ECV, delivery mode, complications and newborn status after ECV. Methods Analysis of assembled data of 327 consecutive ECVs in the third trimester was done. Results The total success rate was 56.6%. After a successful ECV, 85.9% of the fetuses were delivered vaginally. Logistic regression analysis of background factors leading to a successful ECV showed that tocolysis with ritodrine and anterior placenta were each significantly correlated with the rate of successful version. No severe complications were registered during the ECVs, and all babies had normal Apgar scores at delivery. Conclusion These findings suggest that attempting an ECV in breech presentations, once or even twice, seems to be an appropriate management given that a successful ECV decreases the rate of cesarean section in this group of patients and by doing so, it might also decrease the risk of cesarean sections in future pregnancies.


Assuntos
Apresentação Pélvica , Cesárea , Ritodrina/uso terapêutico , Versão Fetal , Adulto , Índice de Apgar , Apresentação Pélvica/diagnóstico , Apresentação Pélvica/epidemiologia , Apresentação Pélvica/terapia , Cesárea/métodos , Cesárea/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Prognóstico , Espanha/epidemiologia , Tocolíticos/uso terapêutico , Resultado do Tratamento , Versão Fetal/efeitos adversos , Versão Fetal/métodos , Versão Fetal/estatística & dados numéricos
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