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Ronald F Lamont - One of the best experts on this subject based on the ideXlab platform.
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Safety and Efficacy of Tocolytics for the Treatment of Spontaneous Preterm Labour
Current pharmaceutical design, 2019Co-Authors: Ronald F Lamont, Jan Stener JørgensenAbstract:Background Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using Tocolytics to inhibit spontaneous preterm labour. Objective We have reviewed the evidence concerning the safety and efficacy of various classes of Tocolytic agents. Results The evidence to support the use of magnesium sulfate or nitric oxide donors as a Tocolytic is poor. Compared to placebo or no treatment, there is evidence to support the efficacy of calcium channel blockers (mainly nifedipine), prostaglandin synthetase inhibitors (mainly indomethacin and sulindac), oxytocin receptor antagonists (mainly atosiban) and β2-agonists (mainly ritodrine, terbutaline, salbutamol and fenoterol). Maternal safety concerns have reduced the use of β2-agonists. Fetal safety and gestational age restrictions have largely condemned prostaglandin synthetase inhibitors to second-line therapy. First-line therapy in Europe and other parts of the world outside the USA and Australia is limited to calcium channel blockers and oxytocin receptor antagonists. With respect to efficacy, atosiban and nifedipine are similar, but the robustness of the evidence favours atosiban. With respect to safety, atosiban is clearly the safest Tocolytic as there are fetomaternal concerns with nifedipine, particularly in high daily doses. Conclusion The perfect Tocolytic that is uniformly effective and safe does not exist. Cost, licensing and informed consent are considerations involved in the choice. Efforts continue to develop and introduce other or better agents, including novel compounds such as progesterone, PGF2α antagonists and statins.
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The safety of Tocolytics used for the inhibition of preterm labour
Expert opinion on drug safety, 2016Co-Authors: Callum D Lamont, Jan Stener Jørgensen, Ronald F LamontAbstract:ABSTRACTIntroduction: Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%.Areas covered: Following a systematic review of the literature, we have provided an overview of the use of Tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various Tocolytic agents currently in use.Expert opinion: No Tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β2-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base...
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Preterm labor: current Tocolytic options for the treatment of preterm labor
Expert opinion on pharmacotherapy, 2014Co-Authors: Jan Stener Jørgensen, Louise Katrine Kjær Weile, Ronald F LamontAbstract:While Tocolytic therapy may not be indicated in all cases of spontaneous preterm labor (SPTL), the evidence that they are superior to placebo is robust. The perfect Tocolytic that is 100% efficacious and 100% safe does not exist and efforts should continue to develop and introduce safer and more effective agents. A reduction in the rate of neonatal mortality and morbidity using tocolysis has not been shown but no Tocolytic study has been powered by numbers sufficient to demonstrate such an effect. Tocolytics can delay delivery long enough to administer a course of antepartum glucocorticoids and arrange in utero transfer to a center with neonatal intensive care facilities, both of which reduce neonatal mortality and morbidity. Few Tocolytics (β₂-agonists and atosiban) are licensed for use as Tocolytics and only one was developed specifically to treat preterm labor (atosiban). Accordingly, most Tocolytics have multi-organ adverse effects. Currently, based on the evidence of safety and efficacy, atosiban should be the first-choice Tocolytic for the treatment of SPTL to prevent or delay preterm birth.
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developments in the pharmacotherapeutic management of spontaneous preterm labor
Expert Opinion on Pharmacotherapy, 2008Co-Authors: K Ronald Y Kam, Ronald F LamontAbstract:Background: Preterm birth is the major cause of perinatal mortality and morbidity in the developed world. Objective: The aim of this study was to establish the importance of preterm birth and the huge healthcare costs involved and review the pathophysiology of preterm labor and the use of antepartum glucocorticoids, which are the main reason why Tocolytics are used to prevent or delay preterm birth. The study also reviewed the range of Tocolytics available, their mode of action and the evidence for their efficacy and fetomaternal safety. Methods: An extensive review of the literature using well-recognized and accepted scientific search engines was employed. Results/conclusions: The perfect Tocolytic does not exist. The evidence to support the use of magnesium sulfate as a Tocolytic is poor. The use of β-agonists is decreasing worldwide as clinicians move to nifedipine or atosiban, which are as effective but much safer. Although nifedipine is cheaper than atosiban and can be administered orally, the eviden...
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Atosiban as a Tocolytic for the treatment of spontaneous preterm labor
Expert Review of Obstetrics & Gynecology, 2008Co-Authors: Ronald F Lamont, Ky Ronald KamAbstract:Preterm birth is the major cause of perinatal mortality and morbidity in the developed world, imposing a huge burden on healthcare costs. Tocolytic drugs inhibit contractions and delay delivery in the hope of improving survival and preventing handicap. Historically, most Tocolytics were not initially developed to treat preterm labor, and so are not uterospecific and have multiorgan side effects. Atosiban (Tractocile®) is a vasopressin-oxytocin receptor antagonist, which is much more uterospecific than previous Tocolytics, and, consequently has placebo-level side effects. Atosiban has a strong evidence base and is a significant addition to the treatment options for preterm labor and should be used for first-line therapy.
David R. Cool - One of the best experts on this subject based on the ideXlab platform.
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Effect of Tocolytics on Surfactant Secretion When Administered with Betamethasone: An in Vitro Study.
American journal of perinatology, 2015Co-Authors: Ziad A. Haidar, Baha M. Sibai, Jiri Sonek, Shamili Sammohi, David S. Mckenna, William C. Grunwald, David R. CoolAbstract:Objective To analyze the amount of surfactant protein (SP)-B and lecithin/sphingomyelin (L/S) ratio in response to betamethasone (BMS) alone as compared with magnesium sulfate (Mg 2+ ), indomethacin (Indo), and nifedipine (Nif) with or without BMS. Study design NCI-H441 human lung cells were grown and distributed into eight plates. BMS and Tocolytics were added and the final plates were: control, BMS only, and each Tocolytic ± BMS. Cells were stained with SP-B antibodies and relative fluorescence was measured. Lipids were also extracted, identified, and examined for relative densities. The L/S ratio was calculated. Results Nine independent measurements were obtained for each plate. The protein analysis revealed that among all eight plates, SP-B levels were highest among BMS only. There was a nonsignificant decrease in SP-B in each of the combinations of Tocolytics + BMS as compared with BMS only. Compared with BMS only, L/S ratio was decreased in Mg 2+ + BMS ( p = 0.041), Indo + BMS ( p = 0.042), and Nif + BMS ( p = 0.025). Conclusion In our in vitro human lung cell model, SP-B and L/S ratio increased in response to BMS administration alone. The addition of Tocolytics to BMS resulted in no increase in L/S ratio and no changes seen in SP-B production compared with BMS alone.
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84 effect of Tocolytic medications on synthesis and secretion of surfactant in an in vitro human lung cell model
American Journal of Obstetrics and Gynecology, 2015Co-Authors: Ziad A. Haidar, Shamili Sammohi, David R. Cool, David MckennaAbstract:84 Effect of Tocolytic medications on synthesis and secretion of surfactant in an in-vitro human lung cell model Ziad Haidar, Shamili Sammohi, David Cool, David Mckenna UT HealthUniversity of Texas Medical School at Houston, OB/GYN, Houston, TX, Wright State University, OB/GYN, Dayton, OH OBJECTIVE: To compare the effects of magnesium sulfate, nifedipine, and indomethacin on surfactant synthesis and secretion in adult human lung cells STUDY DESIGN: Human adult lung cells (NCI-H441) were grown to confluence in Waymouth’s MB571/5 medium containing 2% Hyclone and 1.5% Cellgro, containing 10,000 unit/ml penicillin G sodium, 10,000 ug/ml streptomycin sulfate, and 25 ug/ml amphotericin B. The plates were then divided into 4 groups, consisting of three Tocolytics and a control. Tissue-equivalent doses of the Tocolytics were used to mimic the steady state in-vivo levels of the following doses and routes of administration: indomethacin: 25mg po q6h, nifedipine 10mg po q6h, and magnesium sulfate 2 g/h IV. Betamethasone (BMZ) was added to each group to achieve a comparable tissue concentration to what is achieved clinically when 12 mg IM is given, and then repeated twenty four hours later. Lipids were extracted from the supernatant and separated on anHP-TLC plate in an organic solvent system. The lipids were primuline stained and examined for relative density under a DyLight 488 nmwith a ChemDocMP imaging camera (Bio-Rad, Hercules, CA) from 1 to 10 seconds, and the best image was saved for evaluation. RESULTS: The primuline stained cells showed an increased amount of surfactant B synthesis in each of the combinations: BMZ+nifedipine, BMZ+magnesium, BMZ+indomethacin. Compared to cells containing BMZ alone, the lipid extraction, which is indicative of the cells’ secretion phase, showed a significant increase with BMZ+magnesium and BMZ+indomethacin and decrease with BMZ+nifedipine CONCLUSION: This in-vitro human adult lung cell model demonstrated significant effects on surfactant synthesis and secretion when different Tocolytic agents were given along with betamethasone. It is speculated this may be due to intracellular calcium-dependent interactions with the specific Tocolytic agents in the type II pneumocytes. Further work is required to illicit the exactmechanism responsible for thesefindings.
Ziad A. Haidar - One of the best experts on this subject based on the ideXlab platform.
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Effect of Tocolytics on Surfactant Secretion When Administered with Betamethasone: An in Vitro Study.
American journal of perinatology, 2015Co-Authors: Ziad A. Haidar, Baha M. Sibai, Jiri Sonek, Shamili Sammohi, David S. Mckenna, William C. Grunwald, David R. CoolAbstract:Objective To analyze the amount of surfactant protein (SP)-B and lecithin/sphingomyelin (L/S) ratio in response to betamethasone (BMS) alone as compared with magnesium sulfate (Mg 2+ ), indomethacin (Indo), and nifedipine (Nif) with or without BMS. Study design NCI-H441 human lung cells were grown and distributed into eight plates. BMS and Tocolytics were added and the final plates were: control, BMS only, and each Tocolytic ± BMS. Cells were stained with SP-B antibodies and relative fluorescence was measured. Lipids were also extracted, identified, and examined for relative densities. The L/S ratio was calculated. Results Nine independent measurements were obtained for each plate. The protein analysis revealed that among all eight plates, SP-B levels were highest among BMS only. There was a nonsignificant decrease in SP-B in each of the combinations of Tocolytics + BMS as compared with BMS only. Compared with BMS only, L/S ratio was decreased in Mg 2+ + BMS ( p = 0.041), Indo + BMS ( p = 0.042), and Nif + BMS ( p = 0.025). Conclusion In our in vitro human lung cell model, SP-B and L/S ratio increased in response to BMS administration alone. The addition of Tocolytics to BMS resulted in no increase in L/S ratio and no changes seen in SP-B production compared with BMS alone.
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84 effect of Tocolytic medications on synthesis and secretion of surfactant in an in vitro human lung cell model
American Journal of Obstetrics and Gynecology, 2015Co-Authors: Ziad A. Haidar, Shamili Sammohi, David R. Cool, David MckennaAbstract:84 Effect of Tocolytic medications on synthesis and secretion of surfactant in an in-vitro human lung cell model Ziad Haidar, Shamili Sammohi, David Cool, David Mckenna UT HealthUniversity of Texas Medical School at Houston, OB/GYN, Houston, TX, Wright State University, OB/GYN, Dayton, OH OBJECTIVE: To compare the effects of magnesium sulfate, nifedipine, and indomethacin on surfactant synthesis and secretion in adult human lung cells STUDY DESIGN: Human adult lung cells (NCI-H441) were grown to confluence in Waymouth’s MB571/5 medium containing 2% Hyclone and 1.5% Cellgro, containing 10,000 unit/ml penicillin G sodium, 10,000 ug/ml streptomycin sulfate, and 25 ug/ml amphotericin B. The plates were then divided into 4 groups, consisting of three Tocolytics and a control. Tissue-equivalent doses of the Tocolytics were used to mimic the steady state in-vivo levels of the following doses and routes of administration: indomethacin: 25mg po q6h, nifedipine 10mg po q6h, and magnesium sulfate 2 g/h IV. Betamethasone (BMZ) was added to each group to achieve a comparable tissue concentration to what is achieved clinically when 12 mg IM is given, and then repeated twenty four hours later. Lipids were extracted from the supernatant and separated on anHP-TLC plate in an organic solvent system. The lipids were primuline stained and examined for relative density under a DyLight 488 nmwith a ChemDocMP imaging camera (Bio-Rad, Hercules, CA) from 1 to 10 seconds, and the best image was saved for evaluation. RESULTS: The primuline stained cells showed an increased amount of surfactant B synthesis in each of the combinations: BMZ+nifedipine, BMZ+magnesium, BMZ+indomethacin. Compared to cells containing BMZ alone, the lipid extraction, which is indicative of the cells’ secretion phase, showed a significant increase with BMZ+magnesium and BMZ+indomethacin and decrease with BMZ+nifedipine CONCLUSION: This in-vitro human adult lung cell model demonstrated significant effects on surfactant synthesis and secretion when different Tocolytic agents were given along with betamethasone. It is speculated this may be due to intracellular calcium-dependent interactions with the specific Tocolytic agents in the type II pneumocytes. Further work is required to illicit the exactmechanism responsible for thesefindings.
A Ohlsson - One of the best experts on this subject based on the ideXlab platform.
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Tocolytics for preterm labor: a systematic review.
Obstetrics and gynecology, 1999Co-Authors: K Gyetvai, M E Hannah, E D Hodnett, A OhlssonAbstract:To examine the effectiveness of any Tocolytic compared with a placebo or no Tocolytic for preterm labor. We checked MEDLINE (1966-1998) and the Cochrane Controlled Trials Register for articles, using the search terms "randomized controlled trial" (RCT), "preterm labor," "tocolysis," "betamimetics," "ritodrine," "terbutaline," "hexaprenaline," "isoxuprine," "prostaglandin synthetase inhibitors," "indomethacin," "sulindac," "calcium channel blockers," "nifedipine," "oxytocin receptor blockers," "atosiban," "nitroglceride," and "magnesium sulfate." We included all RCTs that compared effect of a Tocolytic with a placebo or no Tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria. Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of Tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with Tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment. Although Tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.
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Tocolytics for preterm labor: a systematic review.
Obstetrics & Gynecology, 1999Co-Authors: K Gyetvai, M E Hannah, E D Hodnett, A OhlssonAbstract:Abstract Objective: To examine the effectiveness of any Tocolytic compared with a placebo or no Tocolytic for preterm labor. Data Sources: We checked MEDLINE (1966–1998) and the Cochrane Controlled Trials Register for articles, using the search terms “randomized controlled trial” (RCT), “preterm labor,” “tocolysis,” “betamimetics,” “ritodrine,” “terbutaline,” “hexaprenaline,” “isoxuprine,” “prostaglandin synthetase inhibitors,” “indomethacin,” “sulindac,” “calcium channel blockers,” “nifedipine,” “oxytocin receptor blockers,” “atosiban,” “nitroglceride,” and “magnesium sulfate.” Methods of Study Selection: We included all RCTs that compared effect of a Tocolytic with a placebo or no Tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria. Tabulation, Integration, and Results: Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of Tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with Tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment. Conclusion: Although Tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.
Shamili Sammohi - One of the best experts on this subject based on the ideXlab platform.
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Effect of Tocolytics on Surfactant Secretion When Administered with Betamethasone: An in Vitro Study.
American journal of perinatology, 2015Co-Authors: Ziad A. Haidar, Baha M. Sibai, Jiri Sonek, Shamili Sammohi, David S. Mckenna, William C. Grunwald, David R. CoolAbstract:Objective To analyze the amount of surfactant protein (SP)-B and lecithin/sphingomyelin (L/S) ratio in response to betamethasone (BMS) alone as compared with magnesium sulfate (Mg 2+ ), indomethacin (Indo), and nifedipine (Nif) with or without BMS. Study design NCI-H441 human lung cells were grown and distributed into eight plates. BMS and Tocolytics were added and the final plates were: control, BMS only, and each Tocolytic ± BMS. Cells were stained with SP-B antibodies and relative fluorescence was measured. Lipids were also extracted, identified, and examined for relative densities. The L/S ratio was calculated. Results Nine independent measurements were obtained for each plate. The protein analysis revealed that among all eight plates, SP-B levels were highest among BMS only. There was a nonsignificant decrease in SP-B in each of the combinations of Tocolytics + BMS as compared with BMS only. Compared with BMS only, L/S ratio was decreased in Mg 2+ + BMS ( p = 0.041), Indo + BMS ( p = 0.042), and Nif + BMS ( p = 0.025). Conclusion In our in vitro human lung cell model, SP-B and L/S ratio increased in response to BMS administration alone. The addition of Tocolytics to BMS resulted in no increase in L/S ratio and no changes seen in SP-B production compared with BMS alone.
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84 effect of Tocolytic medications on synthesis and secretion of surfactant in an in vitro human lung cell model
American Journal of Obstetrics and Gynecology, 2015Co-Authors: Ziad A. Haidar, Shamili Sammohi, David R. Cool, David MckennaAbstract:84 Effect of Tocolytic medications on synthesis and secretion of surfactant in an in-vitro human lung cell model Ziad Haidar, Shamili Sammohi, David Cool, David Mckenna UT HealthUniversity of Texas Medical School at Houston, OB/GYN, Houston, TX, Wright State University, OB/GYN, Dayton, OH OBJECTIVE: To compare the effects of magnesium sulfate, nifedipine, and indomethacin on surfactant synthesis and secretion in adult human lung cells STUDY DESIGN: Human adult lung cells (NCI-H441) were grown to confluence in Waymouth’s MB571/5 medium containing 2% Hyclone and 1.5% Cellgro, containing 10,000 unit/ml penicillin G sodium, 10,000 ug/ml streptomycin sulfate, and 25 ug/ml amphotericin B. The plates were then divided into 4 groups, consisting of three Tocolytics and a control. Tissue-equivalent doses of the Tocolytics were used to mimic the steady state in-vivo levels of the following doses and routes of administration: indomethacin: 25mg po q6h, nifedipine 10mg po q6h, and magnesium sulfate 2 g/h IV. Betamethasone (BMZ) was added to each group to achieve a comparable tissue concentration to what is achieved clinically when 12 mg IM is given, and then repeated twenty four hours later. Lipids were extracted from the supernatant and separated on anHP-TLC plate in an organic solvent system. The lipids were primuline stained and examined for relative density under a DyLight 488 nmwith a ChemDocMP imaging camera (Bio-Rad, Hercules, CA) from 1 to 10 seconds, and the best image was saved for evaluation. RESULTS: The primuline stained cells showed an increased amount of surfactant B synthesis in each of the combinations: BMZ+nifedipine, BMZ+magnesium, BMZ+indomethacin. Compared to cells containing BMZ alone, the lipid extraction, which is indicative of the cells’ secretion phase, showed a significant increase with BMZ+magnesium and BMZ+indomethacin and decrease with BMZ+nifedipine CONCLUSION: This in-vitro human adult lung cell model demonstrated significant effects on surfactant synthesis and secretion when different Tocolytic agents were given along with betamethasone. It is speculated this may be due to intracellular calcium-dependent interactions with the specific Tocolytic agents in the type II pneumocytes. Further work is required to illicit the exactmechanism responsible for thesefindings.
