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BMC Genetics Nov 2017Ritodrine, a tocolytic β2-agonist, has been used extensively in Europe and Asia despite its safety concerns. This study was designed to identify associations between...
BACKGROUND
Ritodrine, a tocolytic β2-agonist, has been used extensively in Europe and Asia despite its safety concerns. This study was designed to identify associations between β2-adrenergic receptor (ADRB2) polymorphisms and adverse drug events (ADEs) in patients with preterm labor treated with ritodrine.
RESULTS
This follow-up study was prospectively conducted at Ewha Womans University Mokdong Hospital in Korea. Five single nucleotide polymorphisms (SNPs) of the ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) were analyzed in 186 pregnant women with preterm labor. Patients with the AA genotype of rs1042717 had significantly lower incidence of ADEs compared to those with the G allele (p = 0.009). In multivariate analysis, one of the predictors of ADEs was the maximum infusion rate of ritodrine (AOR 4.47, 95% CI 1.31-15.25). Rs1042719 was also a significant factor for ritodrine-induced ADEs. The CC genotype carriers had 78% decreased risk of ADEs compared to those with other genotypes.
CONCLUSIONS
This study demonstrates that ADEs induced by ritodrine are associated with ADRB2 gene polymorphisms, as well as the infusion rate of ritodrine in pregnant women with preterm labor.
Topics: Administration, Intravenous; Adrenergic beta-2 Receptor Agonists; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Humans; Obstetric Labor, Premature; Polymorphism, Single Nucleotide; Pregnancy; Receptors, Adrenergic, beta-2; Ritodrine
PubMed: 29132297
DOI: 10.1186/s12863-017-0565-8 -
Journal of Medical Case Reports Mar 2021We report a case of pulmonary edema induced by tocolytic agents that was successfully managed with noninvasive positive-pressure ventilation (NPPV) and resulted in...
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.
Topics: Adult; Cesarean Section; Female; Humans; Positive-Pressure Respiration; Pregnancy; Pulmonary Edema; Ritodrine; Tocolytic Agents
PubMed: 33743806
DOI: 10.1186/s13256-021-02704-w -
British Journal of Pharmacology Sep 19901. The nature of the adrenoceptors mediating the inhibitory action of noradrenaline, ritodrine and salbutamol on the spontaneous activity of longitudinal muscle of the...
1. The nature of the adrenoceptors mediating the inhibitory action of noradrenaline, ritodrine and salbutamol on the spontaneous activity of longitudinal muscle of the rabbit jejunum in vitro was investigated by use of a range of adrenoceptor antagonists. 2. The actions of ritodrine and salbutamol were antagonized competitively by propranolol. The pA2 values of 6.4 and 6.6 respectively were smaller than those found elsewhere for beta 1- and beta 2-adrenoceptors. 3. In contrast, the responses to ritodrine and salbutamol were antagonized only by high concentrations (greater than 2.7 microM) of phentolamine and were unaffected by yohimbine (2.6 microM), mepyramine (2.5 microM) or cimetidine (4.0 microM). 4. Ritodrine which is less potent than salbutamol in tissues with typical beta 2-adrenoceptors was found to be 8 times more potent than salbutamol in the rabbit jejunum. 5. It is suggested that in the rabbit jejunum ritodrine and salbutamol may act at an atypical beta-adrenoceptor, at which propranolol is a competitive but not very potent antagonist.
Topics: Albuterol; Animals; Cimetidine; Female; In Vitro Techniques; Jejunum; Male; Muscle Contraction; Muscle, Smooth; Norepinephrine; Pyrilamine; Rabbits; Receptors, Adrenergic, beta; Ritodrine; Yohimbine
PubMed: 2178019
DOI: 10.1111/j.1476-5381.1990.tb12083.x -
Yakugaku Zasshi : Journal of the... Jan 2011The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from...
The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.
Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Autoimmune Diseases; Case-Control Studies; Child; Databases, Factual; Female; Humans; Kidney Diseases; Leukopenia; Logistic Models; Male; Methimazole; Methotrexate; Middle Aged; Risk Factors; Ritodrine; Sex Factors; Ticlopidine; Young Adult
PubMed: 21212623
DOI: 10.1248/yakushi.131.139 -
Journal of Pharmaceutical Health Care... 2019Ritodrine hydrochloride (RD), a β2-adrenergic agonist, is widely used as a tocolytic medication to suppress premature labor, but can cause neonatal hypoglycemia, a...
BACKGROUND
Ritodrine hydrochloride (RD), a β2-adrenergic agonist, is widely used as a tocolytic medication to suppress premature labor, but can cause neonatal hypoglycemia, a potentially severe side effect. We examined the incidence and risk factors of neonatal hypoglycemia following maternal intravenous administration of RD.
METHODS
This was a retrospective study of neonates, who had birth weight of ≥2000 g and were delivered at 36 weeks gestation or later in Kanazawa University Hospital from August 2013 to July 2016. We defined neonatal hypoglycemia as blood glucose level < 50 mg/dL. Neonates who were delivered without maternal intravenous RD or who were delivered 8 days or more after stopping maternal RD or who received oral RD were defined as the RD non-administration group, while those delivered within 7 days after stopping maternal RD were defined as the RD intravenous administration group. We examined the incidence and risk factors of RD-induced neonatal hypoglycemia by comparing these two groups.
RESULTS
We enrolled 603 neonates in this study; 504 (83.6%) showed no neonatal hypoglycemia, while 99 (16.4%) exhibited neonatal hypoglycemia. The incidence of neonatal hypoglycemia was significantly higher (61.7%; 58/94) in the RD intravenous administration group than in the RD non-administration group (8.1%; 41/509) ( < 0.001). Binomial logistic regression analysis in the RD intravenous administration group showed that maternal age over 35 years (AOR: 3.385; 95% CI, 1.082-10.588, = 0.036) and the interval to delivery from stopping intravenous administration of RD (AOR: 0.974; 95% CI, 0.953-0.996, = 0.020) were independent factors associated with neonatal hypoglycemia. The cut-off value of the interval to predict the incidence of neonatal hypoglycemia was about 6 h (sensitivity 82.8%, specificity 63.9%).
CONCLUSIONS
The incidence of neonatal hypoglycemia was significantly increased by maternal intravenous administration of RD. We newly identified maternal age (over 35 years) and the interval to delivery from stopping intravenous administration of RD (within 6 h) as independent risk factors for neonatal hypoglycemia following maternal intravenous administration of RD. In cases with these risk factors, careful blood glucose monitoring is recommended for early detection and treatment of neonatal hypoglycemia.
PubMed: 31019720
DOI: 10.1186/s40780-019-0137-3 -
Obstetrics and Gynecology International 2014Creatine kinase (CK), lactate dehydrogenase (LDH), and amylase levels of preterm infants following long-term tocolysis in pregnant women are limited. The objective of...
Creatine kinase (CK), lactate dehydrogenase (LDH), and amylase levels of preterm infants following long-term tocolysis in pregnant women are limited. The objective of this study was to determine if the tocolytic therapy affects CK, LDH, and amylase levels in the umbilical blood. This study included 215 preterm infants born to women treated with and without ritodrine hydrochloride. CK, LDH, and amylase levels in the umbilical blood at delivery were determined. Infants were divided according to the ritodrine tocolysis, as follows: Group A (n = 91), not exposed to ritodrine; Group B (n = 44), IV ritodrine for <1 week; Group C (n = 80), IV ritodrine for ≥1 week. The CK concentration in cord blood of Group C (198.8 ± 14.2 IU/L) was significantly higher in comparison with Group A (155.0 ± 7.3 IU/L, P < 0.05). There was no significant difference in LDH and amylase levels in the three groups. The CK significantly correlated with gestational age (r = 0.42, P < 0.01) and birth weight (r = 0.38, P < 0.01). LDH and amylase levels did not change with gestational age nor birth weight. In conclusion, long-term ritodrine tocolysis leads to increased umbilical blood CK level.
PubMed: 24693289
DOI: 10.1155/2014/278379 -
Japanese Journal of Pharmacology Dec 1984Ritodrine hydrochloride (ritodrine) has been effectively prescribed for the prevention of premature labor. The present study was carried out to investigate the mode of...
Ritodrine hydrochloride (ritodrine) has been effectively prescribed for the prevention of premature labor. The present study was carried out to investigate the mode of action of ritodrine on the uterus and heart in comparison with those of isoxsuprine and isoproterenol. 1) Ritodrine (10(-8)-10(-6) M) suppressed the spontaneous motility of pregnant rat uterus and showed positive chronotropic action at the doses of 10(-6)-10(-4) M in guinea-pig atria. 2) In the Ca2+-free, K+-rich Tyrode solution, ritodrine suppressed the Ca2+ induced contracture of pregnant rat uterus, while it potentiated the carbachol induced contraction. 3) Ritodrine increased the amount of cyclic AMP in the uterus but not in heart. This action of ritodrine was suppressed by pretreatment with propranolol (10(-6) M). 4) These results suggest that ritodrine causes actions through activation of cyclic AMP production, as in the case of isoproterenol, and it acts more selectively on beta 2-adrenoceptors than on beta 1-adrenoceptors.
Topics: Adrenergic beta-Agonists; Animals; Calcium; Carbachol; Cyclic AMP; Female; Guinea Pigs; Heart Rate; In Vitro Techniques; Isoproterenol; Isoxsuprine; Myocardium; Pregnancy; Propanolamines; Rats; Rats, Inbred Strains; Ritodrine; Uterine Contraction; Uterus; Verapamil
PubMed: 6151996
DOI: 10.1254/jjp.36.477 -
Journal de Gynecologie, Obstetrique Et... Nov 2002Spontaneous prematurity is more frequent in multiple than singleton pregnancies. It is estimated that 72% of the multiple pregnancies delivered before 33 weeks are... (Review)
Review
Spontaneous prematurity is more frequent in multiple than singleton pregnancies. It is estimated that 72% of the multiple pregnancies delivered before 33 weeks are spontaneous births, compared with 58% among singletons (NP3). As in singleton pregnancies, uterine contractions, close together, often precede preterm delivery by several days (NP2). The benefits of home tocodynamometry for patients who have already been hospitalized for threatened preterm delivery (TPD) (NP4) is difficult to assess from the data currently available, but it has not been shown to provide any benefits in a population of asymptomatic twin pregnancies (NP1). Cervical ultrasound appears to have good predictive value for preterm delivery when performed for TPD (NP3), although again few data are available. The efficacy of tocolysis appears similar to that for singleton pregnancies (NP3). Although the lack of data prevents us from judging the efficacy of tocolytics such as calcium channel blockers or oxytocin antagonists, it seems logical to use them as first-line drugs, especially because of the increased risk of pulmonary edema in multiple pregnancies with Bmimetics (NP3). Antenatal corticosteroid therapy appears to be less beneficial in multiple than singleton pregnancies (NP3). Pharmacological studies suggest that the dose currently used may be insufficient for multiple pregnancies (NP3). While awaiting results from clinical studies comparing the efficacy of higher doses, we must for now recommend antenatal corticosteroid therapy only at the usual doses. While the rate of in utero transfers to level III facilities is nearly 85% in the case of severe TPD (NP4), this practice must be encouraged still more in view of the benefits of inborn status compared with postnatal transfer. Finally, delayed-interval delivery is a relatively rare obstetrical practice that should be considered on a case-by-case basis when the first fetus is born before 26 weeks. This approach requires tocolysis and antibiotic therapy. The usefulness of cerclage in this situation has yet to be demonstrated. A delayed-interval delivery can prolong the pregnancy by an average of 15 to 30 days (NP4).
Topics: Adrenal Cortex Hormones; Drug Therapy, Combination; Female; France; Humans; Infant, Newborn; Nifedipine; Obstetric Labor, Premature; Practice Guidelines as Topic; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple; Ritodrine; Tocolytic Agents; Ultrasonography, Prenatal; Vasotocin
PubMed: 12454633
DOI: No ID Found -
Journal de Gynecologie, Obstetrique Et... Nov 2002Because criteria used for the prediction of preterm labor are poorly effective, many patients receive tocolytic therapy in excess during pregnancy. Beta-mimetic agonists... (Review)
Review
Because criteria used for the prediction of preterm labor are poorly effective, many patients receive tocolytic therapy in excess during pregnancy. Beta-mimetic agonists are the reference tocolytic drugs in most countries. Their efficacy in prolonging pregnancy compared to a placebo is proven although no benefit in neonatal morbidity or mortality has been demonstrated. Beta-mimetics have many contraindications, and side-effects are frequent. Serious complications such as pulmonary edema and maternal deaths, though rare, have been reported. Recent research has focused on tocolytic drugs with similar efficacy to beta-mimetics but with less side effects. Calcium-channel-blockers and oxytocin antagonists have been compared with beta-agonists in randomized trials. Both have demonstrated similar efficacy in the prolongation of pregnancy for at least 48 hours. Contrary to beta-mimetics, very few interruptions of treatment have been observed with these treatments. Other tocolytic drugs such as cyclooxygenase inhibitors, although effective in prolonging pregnancy, have unacceptable fetal side effects. Progesterone, antispasmodic drugs and magnesium sulfate have been widely used but their efficacy has not been demonstrated. More recent treatments such as NO-donors and cyclooxygenase-II specific antagonists are not sufficiently evaluated. In conclusion, three main classes may be used as first line tocolytic therapy, beta-adrenergic agonists, calcium-channel-blockers, and oxytocin antagonists. The choice among these treatments may be based on contraindications to beta-mimetics, side-effects of the treatment, or even economic reasons.
Topics: Clinical Trials as Topic; Female; France; Humans; Nifedipine; Obstetric Labor, Premature; Practice Guidelines as Topic; Pregnancy; Ritodrine; Tocolytic Agents; Treatment Outcome; Vasotocin
PubMed: 12454631
DOI: No ID Found -
Journal of Nippon Medical School =... 2011A 27-year-old nulligravida woman without a history of dermatosis was hospitalized for threatened preterm labor at 29 weeks' gestation; therefore, continuous infusion of...
A 27-year-old nulligravida woman without a history of dermatosis was hospitalized for threatened preterm labor at 29 weeks' gestation; therefore, continuous infusion of ritodrine hydrochloride was started. At 31 weeks' gestation, erythematous plaques appeared and spread over the body surface; therefore, a topical steroid preparation was applied. At 32 weeks' gestation, the eruptions developed into irregular annular areas of erythema with multiple pustules accompanied by severe itching, and oral prednisolone treatment was started. Bacterial cultures of the pustules were negative, and a crural cutaneous biopsy revealed Kogoj's spongiform pustules. Based on the clinicopathological findings, the most likely diagnosis was impetigo herpetiformis, which causes cutaneous symptoms closely resembling pustular psoriasis in pregnant females without a history of psoriasis. To rule out ritodrine-induced pustular eruptions, the ritodrine infusion was stopped and treatment with an MgSO(4) preparation was started at 33 weeks' 3 days' gestation; however, the uterine contractions could not be suppressed. Because of the patient's highly edematous, severely painful feet, a cesarean section was performed the same day. Within several days of delivery, the eruptions began to resolve, and no recurrence was observed after treatment with oral prednisolone was stopped 31 days after delivery. On the basis of a positive patch test for ritodrine, we diagnosed pustular drug eruptions caused by ritodrine hydrochloride. Although ritodrine-induced pathognomonic cutaneous eruptions are rare, we would like to emphasize that ritodrine can cause drug-induced pustular eruptions distinctly resembling life-threatening impetigo herpetiformis.
Topics: Abortion, Threatened; Adult; Cesarean Section; Dermatitis Herpetiformis; Diagnosis, Differential; Diagnostic Errors; Drug Eruptions; Female; Humans; Impetigo; Patch Tests; Pregnancy; Pregnancy Complications; Ritodrine; Skin; Tocolytic Agents
PubMed: 22041881
DOI: 10.1272/jnms.78.329