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Journal of Family Medicine and Primary... May 2022To compare the efficacy of oral nifedipine and parenteral isoxsuprine in arresting preterm labor. Considering the paucity of studies comparing these two agents, a...
OBJECTIVE
To compare the efficacy of oral nifedipine and parenteral isoxsuprine in arresting preterm labor. Considering the paucity of studies comparing these two agents, a comparative analysis is obligatory.
MATERIALS AND METHODS
Eighty antenatal women in the gestational age range of 28-37 weeks, with regular uterine contractions, cervical dilatation ≤3 cm, and <50% cervical effacement, admitted with complaints of preterm labor pain were randomized to receive either 40 mg isoxsuprine or 20 mg nifedipine. Efficacy of the drugs was measured in terms of arrest of preterm labor, prolongation of pregnancy, and the days gained by infant before birth.
RESULTS
Isoxsuprine showed increased lowering of systolic blood pressure (SBP), diastolic blood pressure (DBP), and slightly higher maternal pulse rate, but higher fetal pulse rate post-administration in comparison to nifedipine ( < 0.05). Isoxsuprine was significantly associated with more side effects. Pregnancy was more prolonged in the nifedipine group (25 days) than in the isoxsuprine group (19 days) ( < 0.05). The birth weight of neonates in group B was more than that of neonates in group A ( < 0.05). At 5 min after birth, none of the neonates in group B had an Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) abnormal score <7, compared to neonates in group A. Majority of neonates in group A showed tachycardia and respiratory distress syndrome (RDS) (17.5% and 12.5%, respectively), compared to group B (12.5% and 7.5%, respectively). The overall success rate was better in group B (86.8%) compared to group A (80%).
CONCLUSION
Nifedipine was slightly more effective in arresting preterm labor with fewer side effects, compared to isoxsuprine.
PubMed: 35800477
DOI: 10.4103/jfmpc.jfmpc_1696_20 -
Pharmaceutics Aug 2023Ischemic stroke is the second-leading cause of death. Hyperglycemia, which is characteristic of diabetes mellitus, contributes to the development of endothelial...
Ischemic stroke is the second-leading cause of death. Hyperglycemia, which is characteristic of diabetes mellitus, contributes to the development of endothelial dysfunction and increases the risk of stroke. Isoxsuprine is an efficient beta-adrenergic agonist that improves blood flow to the ischemic aria and stops the infarct core from growing. However, low bioavailability, a short biological half-life, and first-pass hepatic metabolism reduce the therapeutic efficacy of oral isoxsuprine. Therefore, the authors focused on developing isoxsuprine-loaded liposomes containing ethanol and propylene glycol (ILEP) formulation as nasal drops for the treatment of ischemic stroke in diabetic patients. Different ILEP formulations were optimized using Design Expert software, and the selected formulation was examined in vivo for its anti-stroke effect using a rat model of diabetes and stroke. The optimized ILEP, composed of 15% propylene glycol, 0.16% cholesterol, 10% ethanol, and 3.29% phospholipid, improved the sustainability, permeation, and targeting of isoxsuprine. Furthermore, the in vivo studies verified the improved neurological behavior and decreased dead shrunken neurons and vascular congestion of the rats treated with the optimized ILEP formulation, demonstrating its anti-stroke activity. In conclusion, our study found that treatment with an optimized ILEP formulation prevented the initiation and severity of stroke, especially in diabetic patients.
PubMed: 37765211
DOI: 10.3390/pharmaceutics15092242 -
The Cochrane Database of Systematic... Jan 2021The frequency of skin ulceration makes an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the... (Review)
Review
BACKGROUND
The frequency of skin ulceration makes an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. This is an update of a previously published Cochrane Review.
OBJECTIVES
To assess the clinical effectiveness and harms of interventions for treating leg ulcers in people with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We searched LILACS (1982 to January 2020), ISI Web of Knowledge (1985 to January 2020), and the Clinical Trials Search Portal of the World Health Organization (January 2020). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 13 January 2020; date of the last search of the Cochrane Wounds Group Trials Register: 17 February 2017.
SELECTION CRITERIA
Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. We used GRADE to assess the quality of the evidence.
MAIN RESULTS
Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl cream, arginine-glycine-aspartic acid (RGD) peptide dressing and topical antibiotics). No trials on non-pharmaceutical interventions were included in the review. All trials had an overall unclear or high risk of bias, and drug companies sponsored four of them. We were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the units of randomisation and analysis. Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, only arginine butyrate showed a reduction of ulcer size compared with a control group, mean reduction -5.10 cm² (95% CI -9.65 to -0.55), but we are uncertain whether this reduces ulcer size compared to standard care alone as the certainty of the evidence has been assessed as very low. Three trials reported on complete leg ulcer closure (isoxsuprine, arginine butyrate, RGD peptide matrix; very low quality of evidence). None reported a clinical benefit. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; incidence of amputation or harms.
AUTHORS' CONCLUSIONS
Given the very low quality of the evidence identified in this updated Cochrane Review we are uncertain whether any of the assessed pharmaceutical interventions reduce ulcer size or result in leg ulcer closure in treated participants compared to controls. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having an unclear or high risk of bias. The harm profile of the all interventions remains inconclusive.
Topics: Anemia, Sickle Cell; Bandages; Humans; Leg Ulcer; Quality of Life; Wound Healing
PubMed: 34559425
DOI: 10.1002/14651858.CD008394.pub4 -
The Cochrane Database of Systematic... Dec 2014The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to... (Review)
Review
BACKGROUND
The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease.
OBJECTIVES
To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 21 July 2014; date of the last search of the Cochrane Wounds Group Trials Register: 18 September 2014.
SELECTION CRITERIA
Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data.
MAIN RESULTS
Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl(®) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69; very low quality of evidence). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix; ranging between low and very low quality of evidence). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions.
AUTHORS' CONCLUSIONS
There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports.We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses.This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.
Topics: Actihaemyl; Anemia, Sickle Cell; Anti-Bacterial Agents; Arginine; Bandages; Butyrates; Carnitine; Humans; Isoxsuprine; Leg Ulcer; Oligopeptides; Randomized Controlled Trials as Topic
PubMed: 25485858
DOI: 10.1002/14651858.CD008394.pub3 -
Saudi Pharmaceutical Journal : SPJ :... Jun 2021Sickle-cell disease (SCD) is one of the most common hematologic inherited disorders in Saudi Arabia. Vaso-occlusive pain crisis in SCD is a major cause for emergency... (Review)
Review
INTRODUCTION
Sickle-cell disease (SCD) is one of the most common hematologic inherited disorders in Saudi Arabia. Vaso-occlusive pain crisis in SCD is a major cause for emergency visits and patients' pain may be undertreated. This study presents a narrative literature review of current agents used to manage acute pain crisis in SCD patients presenting to the emergency department in hospitals of Saudi Arabia.
METHOD
We conducted a narrative review on relevant published articles about sickle cell disease pain crisis management in Saudi Arabia and included seven relevant studies based on our inclusion criteria.
RESULTS
Using our search strategy, we included 7 studies Out of 4052. Studies included were conducted in different locations in the country. Four studies were in the Eastern region while only one in Western and One in Central regions. Those studies included around 2441 patients, in total. Morphine was used in 5 studies out of the 7 included. Pethidine was used in 4. One study used Isoxsuprine and another study used tinzaparin.
CONCLUSION
We found that continuous administration of IV morphine accompanied by oral analgesics including NSAIDs and acetaminophen is the most commonly used practice for treating SCD patients presenting with a vaso-occlusive pain crisis. Possible effectiveness of tinzaparin, isoxsuprine, and pethidine as therapeutic options may be considered. However, there was no recommendation for a certain agent to be prescribed. We recommend conducting further clinical randomized-controlled trials.
PubMed: 34194255
DOI: 10.1016/j.jsps.2021.02.001 -
Molecules (Basel, Switzerland) Mar 2019Recently, our research group demonstrated that uvaol and ursolic acid increase NO and H₂S production in aortic tissue. Molecular docking studies showed that both...
Vasodilation Elicited by Isoxsuprine, Identified by High-Throughput Virtual Screening of Compound Libraries, Involves Activation of the NO/cGMP and H₂S/K Pathways and Blockade of α₁-Adrenoceptors and Calcium Channels.
Recently, our research group demonstrated that uvaol and ursolic acid increase NO and H₂S production in aortic tissue. Molecular docking studies showed that both compounds bind with high affinity to endothelial NO synthase (eNOS) and cystathionine gamma-lyase (CSE). The aim of this study was to identify hits with high binding affinity for the triterpene binding-allosteric sites of eNOS and CSE and to evaluate their vasodilator effect. Additionally, the mechanism of action of the most potent compound was explored. A high-throughput virtual screening (HTVS) of 107,373 compounds, obtained from four ZINC database libraries, was performed employing the crystallographic structures of eNOS and CSE. Among the nine top-scoring ligands, isoxsuprine showed the most potent vasodilator effect. Pharmacological evaluation, employing the rat aorta model, indicated that the vasodilation produced by this compound involved activation of the NO/cGMP and H₂S/K signaling pathways and blockade of α₁-adrenoceptors and L-type voltage-dependent Ca channels. Incubation of aorta homogenates in the presence of isoxsuprine caused 2-fold greater levels of H₂S, which supported our preliminary in silico data. This study provides evidence to propose that the vasodilator effect of isoxsuprine involves various mechanisms, which highlights its potential to treat a wide variety of cardiovascular diseases.
Topics: Adenosine Triphosphate; Adrenergic alpha-1 Receptor Antagonists; Calcium Channel Blockers; Cyclic GMP; Dose-Response Relationship, Drug; High-Throughput Screening Assays; Humans; Hydrogen Sulfide; Isoxsuprine; Metabolic Networks and Pathways; Molecular Docking Simulation; Molecular Dynamics Simulation; Nitric Oxide; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vasodilator Agents; Workflow
PubMed: 30862086
DOI: 10.3390/molecules24050987 -
Acta Cirurgica Brasileira Jul 2015To evaluate the effects of isoxsuprine and nicotine on TRAM.
PURPOSE
To evaluate the effects of isoxsuprine and nicotine on TRAM.
METHODS
Forty eight 48 Wistar rats distributed into four Groups (n=12). All rats received medication managed daily for 20 days: saline solution (SA), nicotine solution (NI), isoxsuprine solution (IS) and nicotine solution (NI) + isoxsuprine solution (IS). On day 21st the rats were submitted to the caudally based, right unipedicled TRAM flap and after 48 hours, made the macroscopic evaluation of the surface of the flap, photographic documentation and collection of material for histology. Data from macroscopic evaluation were analyzed by ANOVA and microscopic evaluation by Kruskal-Wallis test, with significance level of 5%.
RESULTS
In the macroscopic evaluation of isoxsuprine Group retail presented absolute numbers: final area (p=0.001*) and viable area (p=0.006*) with the highest values; necrosis (p=0.001*) had the lowest value. Microscopic examination revealed no significant findings in the study of TRAM under the action of isoxsuprine and nicotine to the percentage of necrosis in the left and right cranial and caudal regions.
CONCLUSIONS
There was significant improvement in viability of TRAM using the isoxsuprine solution alone. No influence using nicotine alone and in association with isoxsuprine.
Topics: Animals; Female; Graft Survival; Isoxsuprine; Models, Animal; Myocutaneous Flap; Necrosis; Nicotine; Nicotinic Agonists; Prospective Studies; Rats, Wistar; Rectus Abdominis; Reproducibility of Results; Smoking; Tissue Survival; Vasodilator Agents
PubMed: 26270142
DOI: 10.1590/S0102-865020150070000008 -
Journal of Veterinary Research Dec 2021Wide use is made of β-agonists in therapy due to their smooth muscle-relaxant properties. They also have a side effect of increasing muscle mass. Besides improving...
INTRODUCTION
Wide use is made of β-agonists in therapy due to their smooth muscle-relaxant properties. They also have a side effect of increasing muscle mass. Besides improving oxygen utilisation as bronchodilators, β-agonists increase protein synthesis and promote fat burning. The growth- and performance-enhancing effects are often exploited in illegal use. The guiding objective of this study was to develop a procedure for the determination of β-agonists by a single method in different types of matrices.
MATERIAL AND METHODS
Five grams of homogenised samples were subjected to enzymatic hydrolysis with β-glucuronidase in ammonium acetate, pH 5.2. Purification was performed by solid phase extraction. Analytes were eluted with 10% acetic acid in methanol. The eluted β-agonists were analysed by high-performance liquid chromatography-tandem mass spectrometry.
RESULTS
Validation results met the requirement of the confirmation criteria according to European Commission Decision 2002/657/EC in terms of apparent recoveries (93.2-112.0%), repeatability (3.1-7.1%) and intra-laboratory reproducibility (4.1-8.2%).
CONCLUSION
The method can be successfully applied in the detection and determination of clenbuterol, salbutamol, mabuterol, mapenterol, terbutaline, brombuterol, zilpaterol, isoxsuprine and ractopamine in feed, drinking water, urine, muscle, lung and liver matrices.
PubMed: 35112001
DOI: 10.2478/jvetres-2021-0058 -
The Cochrane Database of Systematic... Dec 2015Twin pregnancies are associated with a high risk of neonatal mortality and morbidity due to an increased rate of preterm birth. Betamimetics can decrease contraction... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Twin pregnancies are associated with a high risk of neonatal mortality and morbidity due to an increased rate of preterm birth. Betamimetics can decrease contraction frequency or delay preterm birth in singleton pregnancies by 24 to 48 hours. The efficacy of oral betamimetics in women with a twin pregnancy is unproven.
OBJECTIVES
To assess the effectiveness of prophylactic oral betamimetics for the prevention of preterm labour and birth for women with twin pregnancies.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group Trials Register (21 September 2015), MEDLINE (January 1966 to 31 July 2015), EMBASE (January 1985 to 31 July 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials in twin pregnancies comparing oral betamimetics with placebo or any intervention with the specific aim of preventing preterm birth. Quasi-randomised controlled trials, cluster-randomised trials and cross-over trials were not eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two authors assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
Overall, the quality of evidence is low for the primary outcomes. All of the included trials had small numbers of participants and few events. Preterm birth, the most important primary outcome, had wide confidence intervals crossing the line of no effect.Six trials (374 twin pregnancies) were included, but only five trials (344 twin pregnancies) contributed data. All trials compared oral betamimetics with placebo.Betamimetics reduced the incidence of preterm labour (two trials, 194 twin pregnancies, risk ratio (RR) 0.37; 95% confidence interval (CI) 0.17 to 0.78; low quality evidence). However, betamimetics did not reduce prelabour rupture of membranes (one trial, 144 twin pregnancies, RR 1.42; 95% CI 0.42 to 4.82; low quality evidence), preterm birth less than 37 weeks' gestation (four trials, 276 twin pregnancies, RR 0.85; 95% CI 0.65 to 1.10; low quality evidence), or less than 34 weeks' gestation (one trial, 144 twin pregnancies, RR 0.47; 95% CI 0.15 to 1.50; low quality evidence). Mean neonatal birthweight in the betamimetic group was significantly higher than in the placebo group (three trials, 478 neonates, mean difference 111.22 g; 95% CI 22.21 to 200.24). Nevertheless, there was no evidence of an effect of betamimetics in reduction of low birthweight (two trials, 366 neonates, average RR 1.19; 95% CI 0.77 to 1.85, random-effects), or small-for-gestational age neonates (two trials, 178 neonates, average RR 0.90; 95% CI 0.41 to 1.99, random-effects). Two trials showed that betamimetics significantly reduced the incidence of respiratory distress syndrome (388 neonates, RR 0.30; 95% CI 0.12 to 0.77), but the difference was not significant when the analysis was adjusted to account for the non-independence of twins (194 twins, RR 0.35; 95% CI 0.11 to 1.16). Three trials showed no evidence of an effect of betamimetics in reducing neonatal mortality, either with the unadjusted analysis, assuming twins are completely independent of each other (452 neonates, average RR 0.90; 95% CI 0.15 to 5.37, random-effects), or in the adjusted analysis, assuming non-independence of twins (226 twins, average RR 0.74; 95% CI 0.23 to 2.38, random-effects). A maternal death was reported in one trial without a significant difference between the groups (144 women, RR 2.84; 95% CI 0.12 to 68.57).
AUTHORS' CONCLUSIONS
There is insufficient evidence to support or refute the use of prophylactic oral betamimetics for preventing preterm birth in women with a twin pregnancy.
Topics: Administration, Oral; Adrenergic beta-Agonists; Adult; Albuterol; Female; Fenoterol; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Isoxsuprine; Pregnancy; Pregnancy, Twin; Premature Birth; Randomized Controlled Trials as Topic; Ritodrine; Terbutaline; Tocolytic Agents
PubMed: 26645888
DOI: 10.1002/14651858.CD004733.pub4 -
Electronic Physician Aug 2015Isoxsuprine (Vasodilan) is a beta-adrenergic that directly affects the vascular smooth muscle and results in peripheral vascular dilation. Isoxsuprine relaxes the...
BACKGROUND
Isoxsuprine (Vasodilan) is a beta-adrenergic that directly affects the vascular smooth muscle and results in peripheral vascular dilation. Isoxsuprine relaxes the uterine smooth muscles and is used for treatment of pre-term labor and dysmenorrhea. Isoxsuprine is used extensively in hospitals and private clinics in Iran; however, few studies have reported its safety and efficacy in the prevention of pre-term labor.
OBJECTIVE
The aim of this study was to assess the effect of maintenance therapy with oral isoxsuprine for the prevention of pre-term labor.
METHODS
We undertook a blinded prospective randomized trial of 70 women with singleton pregnancies who presented in pre-term labor between 26 to 34 weeks of gestation. After arresting the contractions with intravenous magnesium sulfate, the patients were randomized into two groups, with the treatment group receiving oral isoxsuprine until 34 weeks of gestation. Response to treatment was assessed by the progression of the pregnancies in both groups. The data were analyzed using SPSS software.
RESULTS
Our results showed that 14 (40%) of the patients in the case group and 12 (34.29%) of patients in the control group had pre-term births, and there was no significant difference between the two groups (P=0.621). Also four women (11.43%) in the case group and five women (14.29%) in the control group delivered before 34 weeks (P=0.721).
CONCLUSION
Oral isoxsuprine was not effective as a maintenance treatment in preventing pre-term births or in delaying delivery until after 34 weeks. Larger studies are needed to identify the best treatment for pre-term labor.
PubMed: 26396726
DOI: 10.14661/2015.1144-1149