Synthetic Prostaglandin E1 Analogue Research Articles

Misoprostol-induced seizures following self-abortion: a rare, but repeated occurrence

Misoprostol is a synthetic prostaglandin E1 (PGE) analogue used for medical termination of pregnancy, managing miscarriage, inducing labour, cervical ripening, and treating postpartum haemorrhage. Generally, it is safe and well-tolerated, with dose-dependent adverse effects such as nausea, vomiting, diarrhoea, abdominal pain, fever, and headache that usually resolve within a few days. However, seizures are a rare complication, occurring primarily in patients with a history of epilepsy or a predisposition to seizures and is associated with high doses and rapid administration. This case report highlights the repercussions of a misoprostol overdose used for pregnancy termination, leading to seizures induced by hyperthermia. The first patient required temporary invasive ventilation and resuscitation but recovered, whereas the second patient receiving a lower dose, exhibited milder symptoms. Both patients received psychosocial counselling prior to discharge.

Use of prostaglandin E1 analog (misoprostol) to aid cervical dilation in birth induction (a case report)

The cervix is a barrier between the environment and the uterus, composed of longitudinal folds that continue along the uterine folds. Cervical dilation is associated with increased synthesis of prostaglandin E2 (PGE2). Dilatation may fail due to congenital malformations or adhesions of the cervix caused, for example, by previous dystocia or by failure of any mechanisms that regulate cervical relaxation including a reduction in collagen and glycosaminoglycans and an increase in water content and metalloproteinases. Labor induction often requires the ripening of the cervix mechanically or pharmacologically. Oxytocin success may be reduced if the cervix is not favorable or responsive. Misoprostol, a synthetic prostaglandin E1 analog, is widely used in reproduction in cases of oviduct obstruction. It also promotes cervical softening by the dissolution of extracellular collagen. A 17-year-old mixed-breed mare from a private farm in the Middle East presented with abdominal discomfort and signs of imminent delivery, 10th months after embryo transfer. A slight thickening of the uterus-placental junction (7.12mm) was observed during transrectal ultrasound evaluation, but there was no placental detachment. On transabdominal imaging, the absence of a fetal heartbeat, fetal movements, and torsion of the umbilical cord were observed. Imaging evaluations were performed with an ultrasound machine DCS - MyLab™25 GOLD, 5Hzfrequency. Hematological analysis of the mare showed results within normal ranges. Flunixin Meglumine (10mL i.v., Finadyne, 50mg/mL, MSD) was administered before the abortion procedure. After confirmation of fetal death and dystocia in the mare, the cervix dilation process began with a local application of 1mg of misoprostol 200mcg diluted in lubricating gel and mechanical massage. Then, intravenous oxytocin (Syntocin, 10UI/mL, Illium) was started gradually every 5 minutes (5IU, 5IU, 10IU, 10IU). Mild sedation and analgesia was achieved with detomidine (0.6mL i.v., Dormiun V, 10mg/mL, Agener Uniao) and butorphanol (1mL i.v., Torbugesic, 14,58mg/mL, Zoetis). The mare showed signs of delivery before the mechanical rupture of the allantochorion. The position of the fetus (head back and right shoulder flexion) was corrected transvaginally by mechanical maneuver. After removing the fetus, 5 mg of dinoprost (i.m., Lutalyse, 6.71mg/mL, Zoetis) was administered to aid uterine contractility and clearance. The placenta did not have macroscopic changes. The fetus showed an absence of the right posterior limb's first, second, and third phalanges. During fetal necropsy, no other changes were observed. Uterine lavage was performed 24h and 48h after the procedure, using Ringer Lactate Solution (LRS), with 10% iodine (20mL/5L LRS) followed by 20IU oxytocin every eight hours for two consecutive days.

Potentially acute misoprostol toxicity during third-trimester pregnancy: a case report

Background: The International Federation of Gynecology and Obstetrics (FIGO) recommends the dosage of misoprostol for pregnancy termination in >28 weeks is 25 mcg to 100 mcg per-vaginal or sublingual or buccal, every 6 hours, and the maximum dose is 6 mg. Acute misoprostol toxicity is rarely reported, including in the case of pregnant women. This study aims to discuss the effect of potentially acute misoprostol toxicity in pregnant women and the fetus. Case Presentation: A 17 years-old woman, G1, 32 weeks, presented with singleton intrauterine fetal death. The patient previously consumed 14 tabs of oral misoprostol and 4 tabs of misoprostol intravaginally. Her vital signs were within a normal level, his 4x/10'/40", and her fetal heart rhythm was negative. From vaginal touché found complete dilation. The patient led to bear down and born baby boy, demise fetal, 1965-gram, 43 cm, no maceration and placenta born completely. After delivery, the mother was in good condition. Misoprostol is a synthetic analog of prostaglandin E1, which can be used for uterotonics and cervical ripening. In pregnant women, misoprostol toxicity can induce hypertonic uterine contractions, leading to fetal distress and death, rhabdomyolysis, hyperthermia, respiratory alkalosis, hypoxemia, and metabolic acidosis. One article reported maternal death due to upper gastrointestinal bleeding and multiorgan failure. We analyze that intrauterine fetal death may happen because of excessive misoprostol that induces hypertonic uterine contraction, causing fetal distress and leading to fetal demise. Conclusion: Excessive consumption of misoprostol or potentially acute misoprostol during the third-semester pregnancy can lead to harmful effects for both mother and fetus.

Morphofunctional reorganization of plantar aponeurosis in experimental modeling of fasciopathy by synthetic analogue of prostaglandin E1

Foundation. Chronic plantar fasciopathic pain syndrome is a pathology that significantly affects the quality of life of patients of all age categories. Insufficient knowledge of the etiological and pathogenetic factors in the development of fasciopathies explains the multiplicity, and sometimes inconsistency, of conservative and surgical treatment regimens. The choice of the optimal variant of therapeutic or surgical intervention may be associated with experimental modeling of fasciopathies and the study of the dynamics of the pathological process.The aim. To study the morphological changes in structures identical to the human plantar aponeurosis in experimental modeling of fasciopathy in animals.Research methods. The material for the study was fragments of the tendonaponeurotic complex of the foot of laboratory animals (control group: animals with the introduction of physiological sodium chloride solution (n = 12); main group: animals with the introduction of alprostadil (n = 12)). The methods of light microscopy (staining with alcian and toluidine blue, according to Van Gieson, Weigert – Van Gieson and Picro-Mallory) and morphometry were used.Results and discussion. As a result of the study, it was found that the four-fold administration of alprostadil had a significant effect on the structure of the dense fibrous connective tissue of the plantar foot of laboratory animals. The mechanisms of damage (edema, microhemorrhages, infiltration by lymphocytes, plasmocytes and leukocytes, dystrophy by the type of mucoid and fibrinoid swelling, delamination and rupture of collagen fibers), adaptation and regeneration (the appearance of a large number of activated fibrocytes, fibroblasts, microvessels, neoplasm of collagen fibers) were activated. All this together led to spatial focal histotopographic changes, consisting in an increase in the cellular composition of connective tissue structures against the background of a noticeable violation of their spatial orientation.Conclusion. Modeling of fasciopathy using alprostadil was accompanied by the appearance of mosaic reversible and irreversible heteromorphic and heterochronous changes in all connective tissue aponeurotic structures. Such histotopographic changes should be considered as one of the reasons for the clinical manifestations of plantar fasciopathies, causing functional insufficiency and explaining the clinical recurrent nature of the pathological process.

Uterine inflammatory response after misoprostol during estrus and diestrus in commercial embryo donor mares

Uterine tube obstruction is the leading cause of unexplained subfertility in mares. Over the years, numerous techniques were developed to unblock uterine tubes with variable success. In recent years, the administration of misoprostol, a synthetic analog of prostaglandin E1, in the uterus, has regained popularity in equine practice. However, there have been some concerns regarding an exacerbated post-infusion uterine inflammatory response to misoprostol; nonetheless, this has yet to be critically studied. In addition, debate exists when mares should receive misoprostol. This study aimed to determine the uterine inflammatory response in mares after infusion with misoprostol during estrus or diestrus. We hypothesized that misoprostol infusion induces a greater inflammatory response than sham infusion; similarly, diestrus results in a greater inflammatory response than estrus. Forty-four estrous cycles of light breed mares (n=11) were sequentially randomly assigned to receive misoprostol or sham infusion during estrus and diestrus. The misoprostol and sham infusions were performed by directing a flexible pipette (Minitube, Germany) deep into each uterine horns, which received 200mcg of misoprostol diluted in 3 mL of Lactate Ringer's Solution (LRS), whereas the sham inoculation consisted of 3 mL of LRS. The cycles assigned for estrus treatment received it when preovulatory follicles ranged from 28-32 mm, and diestrus cycles were treated eight days post-ovulation. The day after each infusion, mares had uterine lavage performedwith LRS. Uterine edema and intrauterine fluid accumulation were performed by transrectal ultrasonography immediately before (0h), 24, 48, and 72 h after treatments. At similar time points, uterine cytology samples were harvested to count the number of neutrophils in a high-power field (400 ×). Ovulation was hastened with deslorelin (1mg, i.m.) during estrus or the subsequent estrus after diestrus infusion. Mares received 5 mg of dinoprost (i.m.) 24 h after infusion in estrus and diestrus. Statistical analyses were performed with Graph Prisma. Neutrophil counts were analyzed with ANOVA repeated measures and Tukey's as post-hoc. Edema scores and intrauterine fluid accumulation were analyzed with Kruskal-Wallis and Dunn's post-hoc. Embryo recovery rates were evaluated with Fisher's test. There were effects of time (P=0.04) but no effects of group (P=0.96), or stage of the estrous cycle (P=0.26), or interaction between group and time for edema scores (P=0.97). Similarly, there were effects of time (P=0.03) but no effects of group (P=0.32), stage of the estrous cycle (P=0.86), or interactions between group and time or stage of the estrous cycle for neutrophil counts (P=0.87). Uterine fluid scores did not change over time (P=0.39), groups (P=0.22), or stage of the estrous cycle (P=0.77). Embryo recovery was similar for estrus (Misoprostol 46% vs. sham 46%) vs. diestrus (Misoprostol 67% vs. sham 46%) (P>0.05). In conclusion, 200 mcg of misoprostol bilateral administration did not exacerbate uterine inflammation in mares.

A Comparison of Using Oral Misoprostol and Manual Vacuum Aspiration (MVA) in the First Trimester Incomplete Abortion

Background: Misoprostol, a synthetic prostaglandin E1 analogue, may workas an alternative to manual vacuum aspiration (MVA) in incomplete abortion, which is easy to administer orally, andhelps to increase access to post abortion care.Objective: To compare the effectiveness, safety and acceptability by the patients of using oral misoprostol therapy and manual vacuum aspiration technique for the treatment of incomplete abortion in the first trimester of pregnancy.Methods: This cross-sectional study was conducted in Department of Obstetrics & Gynaecology, Sir Salimullah Medical College & Mitford Hospital, Dhaka, Bangladesh, between January and July of 2016. A total of 200 patients (women with incomplete abortion ≤12weeks) were enrolled in the study. 100 Patients were randomly selected and treated with oral misoprostol 600mcg (group I), while the other 100 were treated with manual vacuum aspiration (MVA) (group II). They were followed up for 1-3 days before discharge. Participants were asked to return to the clinic for follow-up after 1 week. In follow-up visit, if abortion was not found complete, an immediate surgical evacuation was performed.Results: The mean age of the participants were 28.59±10.44 and 28.24±9.40 in group I and II respectively. In group I, 94% had complete abortion, while 6% had incomplete abortion or continued pregnancy. However, in group II, 100% had complete abortion (P>0.05). Per vaginal normal and heavy bleeding were 35% and 12% in group I, while 9% and 1% in group II respectively (P<0.001). Pain, nausea, vomiting and gastrointestinal issues were more observed in group I than that of group II (P<0.001). However, incidence of fever, headache and vertigo were similar in both groups (P<0.001). In group I, 98% stated that the treatment was ‘satisfactory/very satisfactory’, while in group II, 99% found the procedure ‘satisfactory/very satisfactory’. The difference between the groups is not statistically significant (P>0.05). In group I, 98% stated that they would select this method again, if needed and recommend it to a friend or relative, while in group II, 88% stated that they would choose this method again and 86% would like to recommend to a friend or relative. The difference between the groups is statistically significant (P<0.001).Conclusion: Our data suggest that oral misoprostol therapy can be used effectively ensuring safety and patients’ satisfaction for treatment of incomplete abortion in the first trimester as compared to manual vacuum aspiration technique.International Journal of Human and Health Sciences Vol. 06 No. 02 April’22 Page: 173-177

Evaluation of Low-dose and High-dose Intravaginal Misoprostol for Induction of Labour: A Randomised, Double-blinded, Single Centre Study

Introduction: Misoprostol is a synthetic prostaglandin E1 analogue widely used for cervical ripening and labour induction. However, misoprostol optimal dose required to induce labour is still controversial. Aim: To determine the efficacy and safety of 25 µg and 50 µg of intravaginal misoprostol for induction of labour at term and to evaluate maternal and neonatal complications. Materials and Methods: The present study was a prospective, randomised, double blind, single centre study carried out during March 2019 to December 2020. All the selected participants were randomised (1:1) to group 1 which received 25 µg of intravaginal misoprostol (n=70) and group 2 received 50 µg of intravaginal misoprostol (n=70). Based on the Bishop’s score, misoprostol was chosen as labour inducing agent. Number of misoprostol doses, mode of delivery, vaginal delivery duration, maternal and neonatal complications was recorded. Statistical significance among study groups were analyzed by using Chi-square test. Results: Postdatism was most frequently reported indication in both the study groups (57.1% and 52.9%). A total of 14 and 4 participants in group 2 and group 1 received only single dose of misoprostol (p<0.01). Participants who received misoprostol 50 µg (n=60, 85.7%) has slightly showed higher vaginal deliveries compared to misoprostol 25 µg (n=57, 81.4%). The mean duration of induction time in group 2 was 10.12 hours and group 1 women showed 13.56 hours (p<0.0001). Maternal and neonatal complications were slightly higher in 50 µg misoprostol group. Maternal complications such as uterine tachysystole (n=4), Postpartum Haemorrhage (PPH) (n=3) and uterine hyperstimulation syndrome (n=2). Neonatal complications with 50 µg misoprostol were Apgar <7 at 1 min (n=4), Apgar <7 at 5 min (n=3), Special Care Baby Unit (SCBU) admissions (n=2) and severe birth asphyxia (n=1). Misoprostol with 25 µg has showed Apgar <7 at 1 min (n=2), Apgar <7 at 5 min (n=2), SCBU admissions (n=1). Conclusion: The efficacy and safety results of 25 µg intravaginal misoprostol were comparable with 50 µg of intravaginal misoprostol for labour induction. The advantages of 50 µg misoprostol were it favours the vaginal deliveries, lesser active induction time and decrease number of misoprostol doses required to induce labour. However, higher dose of misoprostol showed higher frequencies of both maternal and neonatal complications.

Castor oil Induces Morphological Changes in Endometrium and Biochemical Parameters in Pregnant Wistar Rats

Background: Misoprostol is a synthetic prostaglandin E1 analogue, used for the management of miscarriages and labour. Castor oil is a natural plant extract that has been reported to have some abortifacient Properties Objectives: This study investigated the labour induction and abortifacient properties of castor oil, as well as possible effects on the electrolytes and hormones that regulate pregnancy, as well as to compare these effects with a standard labour inducing drug misoprostol, in Wistar rats. Methods: The study was conducted out in 2 phases. The pregnant rats were administered varying Castor oil doses of low (12.4ml/kg), medium (18.6ml/kg) and high (24.8ml/kg), which were compared with misoprostol group as well as a control group. All animals were euthanized on gestational day 15 and day 20 respectively for the two phases and blood samples collected via cardiac puncture from the apex of the heart for hormonal assay, electrolyte and kidney function tests. The uterus was also removed for histological processing. Results: The abortifacient effect of castor oil is dose dependent with high dose castor oil group seen to have significantly reduced serum progesterone level (32.8±4.25 and 40.8±0.70 compared with 51.0±2.00 of controls), resulted in weight loss and interference with kidney function (increase in serum potassium while decrease in sodium electrolytes). Castor oil also exhibited labor inducing properties. Conclusion: Castor oil has the potential to induce abortion. This study has demonstrated a possible usage of castor oil in medical induction of labor in rats as it exerted uterotonic principle on the uterus.

Laser Treatment of Hypopigmentation in Scars: A Review.

Despite history of multiple treatment modalities, repigmentation of hypopigmented scars remains a difficult clinical problem. The purpose of this review is to evaluate the literature on laser and combination laser plus adjunct topical therapy for hypopigmented burn and traumatic scars. A search on PubMed and on Oxford Academic was conducted with additional relevant literature obtained from reference lists. Treatment regimens that address hypopigmentation within scars were reviewed. A combination of nonablative fractional or ablative fractional laser treatment with topical prostaglandin analogue with or without topical retinoid were found to result in superior repigmentation. Reliable improvement of hypopigmentation in scars after laser treatment is challenging. Laser can achieve success in some cases. Ultraviolet laser can achieve modest repigmentation; however, results are short-lived and require continued re-treatment. Modest improvement in pigmentation is seen with nonablative fractional laser or ablative fractional laser alone and enhanced repigmentation is demonstrated when combining fractional laser resurfacing with topical application of synthetic prostaglandin analogues and other known modulators of melanogenesis.

Labour Induction with Misoprostol in German Obstetric Clinics: What Are the Facts on Such Use?

Subject While the synthetic prostaglandin E1 analogue misoprostol is the most effect labour induction agent, its use is off-label for the most part. For this reason, and in view of its potential adverse effects and varying approaches to its administration, the drug has recently once again become a focus of critical attention. The objective of this survey was thus to establish a record of labour induction with misoprostol in German clinics and determine the impact of the negative reporting on everyday obstetric practice. Material and Methods In this cross-sectional study, 635 obstetrics and gynaecology departments in Germany were requested by email to participate in our survey in February/March 2020. Online responses to 19 questions were requested regarding the clinic, use of misoprostol before and after the critical reporting, use of misoprostol (sourcing, method of administration, dosage, monitoring) and other labour induction methods. Results A total of 262 (41.3%) of the clinics solicited for the survey completed the questionnaire. There were no differences regarding the care level (Perinatal Centre Level I, Perinatal Centre Level II, Clinic with Perinatal Focus or Obstetric/Private Clinic; p = 0.2104) or birth counts (p = 0.1845). In most cases, misoprostol was prepared in the clinicʼs own pharmacy (54%) or imported from another country (46%) and administered orally in tablet form (95%). Misoprostol dosage levels varied (25 µg [48%], 50 µg [83%], 75 µg [6%], 100 µg [47%] and > 100 µg [5%]). Most of the clinics used premanufactured tablets/capsules (59%), although Cytotec tablets were also divided (35%) or dissolved in water (5%). Misoprostol administration intervals were mainly every 4 hours (64%) or every 6 hours (30%). CTG checks were run in most cases before and after administration of a dose of misoprostol (78% and 76%) and before and after administration of a dose of prostaglandin E2 (both 88%). Presence of contractions led to no misoprostol (59%) or no prostaglandin E2 (64%) being administered in most cases. The critical reporting resulted in discontinuation of use of misoprostol in 17% of the clinics – mainly smaller obstetric/private clinics with fewer than 1000 births. Labour cocktails were used mainly in obstetric and private clinics (61%). Conclusion Misoprostol is an established agent for labour induction in German clinics. The dosing schemes used vary. Improvements of currently common management practices are required, especially in the area of labour induction (CTG checks before and after administration of labour-inducing medication, no administration of prostaglandin if contractions are ongoing). The discussion of use of misoprostol in the media resulted in stoppage of its use mainly in smaller clinics.

Misoprostol Induced Hyperpyrexia associated with Seizures in Postpartum Parturient: Rare Side Effect and its Management in Critical Care Settings

Misoprostol is a synthetic prostaglandin E1 analogue and has been reccommended as a safe, effective, easy to administer, cost efficient next in line drug after oxytocin, for the treatment and prevention of postpartum haemorrhage (PPH). Notwithstanding, it causes certain undesirable side effects compared to oxytocin such as nausea, vomiting, shivering, diarrhoea and transient fever. Transient pyrexia is commonly related with misoprostol administration, due to shift of hypothalamic set point. However, hyperpyrexia clubbed with seizures is a rare yet self-limiting side effect and requires prompt management strategies. There have been case reports describing fever following misoprostol administration but only few describing hyperpyrexia and even fewer describing with seizures. We report a case of hyperpyrexia associated with delayed presentation of generalised sezuires after administration of rectal misoprotol and its successful management in critical care settings.

Peculiarities and new prospects of management of patients with NSAID-gastropathy on the background of chronic pancreatitis in general-therapy practice

Introduction. The main pharmacological effects of NSAIDs are anti-inflammatory, the onset and conduction of a pain signal, the aggregation of blood elements, neoangiogenesis, cell apoptosis, etc. — make them indispensable in the treatment of inflammatory and degenerative diseases of the joints and spine, in particular osteoarthritis. NSAIDs account for 25% of all medical complications, including bleeding rates (25–40%), which is a serious medical and important socio-economic problem. The risk of developing NSAIDs-gastropathy is determined both by severity of COX-2 inhibitory effect and non-prostaglandin systemic and local effects. Use of proton pump inhibitors, histamine blockers (mainly children and adolescents), and synthetic analogues of prostaglandins, as well as drugs of cytoprotective action, is pathogenetically justified in the treatment of NSAIDs-gastropathy. One of the newest and most economically available, most metabolically high-technological is the vitamin drug Doctovit.
 Aim: to study the effectiveness of Doctovit in the complex therapy of patients with NSAIDs-gastropathy on the background of chronic pancreatitis by analyzing the morphological parameters, indices of antioxidant protection system and endotoxicosis system.
 Materials and methods. 42 patients with NSAID-gastropathy on the background of chronic pancreatitis were examined. Patients, comparable by clinical, gender criteria, severity of NSAID-gastropathy and treatment received — were divided into two groups: I control group (20 patients), 10-day treatment regimen: PPI pantoprazole (Controlok, Nolpase, Pantasan, etc.) 40 mg×2; cancellation of NSAIDs; II main group (22 patients), 10-day treatment regimen: PPI pantoprazole (Controlok, Nolpase, Pantasan, etc.) 40 mg×2; cancellation of NSAIDs; Doctovit 2 tablets per day after meals for 2 months. Compulsory components of medical complexes were outpatient regimen and normotrophic nutrition. All patients with NSAID-gastropathy underwent standardized clinical laboratory examination. At the beginning of the study and two months after the start of treatment EGDS + biopsy from 5 places with histological examination was performed. The level of endotoxicosis was defined by the level of sorption capacity of erythrocytes, which was determined according to A. A. Togaibayev technique. The state of lipid peroxidation was evaluated by the level of malonic aldehyde, the state of antioxidant protection system — by the levels of superoxide dismutase, catalase, SH-groups.
 Results and discussion. Morphological examination of gastric EGD biopsy specimens before and after treatment in the comparison groups showed statistically significant efficacy of the proposed treatment complex with the inclusion of Doctovit in influencing the established pathological features of NSAID-gastropathy. There was a statistically significant improvement in endotoxicosis in both study groups after treatment, but in the II group the positive effect was statistically more significant. The proposed correction programs had a positive effect on the lipid peroxidation, but the correction program used in II group had a statistically significantly better effect.
 Conclusion. In the complex treatment of NSAID-gastropathy on the background of chronic pancreatitis, it is advisable to use the vitamin complex Doctovit 2 tablets per day after meals for 2 months, which has a positive effect on the condition of the gastric mucosa, indices of lipid peroxidation and endotoxicosis.

A randomised prospective observational study comparing outcomes of labour induction and augmentation between high dose oral misoprostol and intracervical dinoprostone

Introduction: Induction of labour is one of the most commonly practiced interventions in obstetrics all over the world with incidence rates between 10-25% in industrialized countries. Misoprostol, a synthetic prostaglandin analogue, is an effective agent for inducing uterine contractions. We undertook this study to compare the efficacy of high dose (50mcg) oral misoprostol and intracervical dinoprostone gel in induction of labour and compare the safety of the drugs in induction of labour.

Thyroid Dysfunction in Patients with Pulmonary Artery Hypertension (PAH): The Effect of Therapies Affecting the Prostanoid Pathway.

Epoprostenol, a synthetic prostaglandin I2 (PGI2) analog, has been the mainstay of treatment for severe pulmonary arterial hypertension (PAH) for the last two decades. Treprostinil, another synthetic prostaglandin analog, and selexipag, an oral selective Inositol Phosphate (IP) prostacyclin receptor agonist, have also been approved for treatment of PAH. Prostacyclin and its analogs cause a variety of side effects in patients with PAH; however, thyroid dysfunction is rarely reported. After treating an index case of thyroid dysfunction occurring after initiation of epoprostenol, we reviewed our databases of PAH patients treated with epoprostenol, treprostinil or selexipag to identify the occurrence of this association. We identified six cases of thyroid dysfunction in our cohort: five after initiation of an intravenous prostacyclin (epoprostenol) and one after initiation of an oral prostacyclin receptor agonist (selexipag). Four of the patients presented with hyperthyroidism and two with a large autoimmune goiter. Graves' disease was seen in three patients, Hashimoto's disease in two patients and thyrotoxicosis in one patient. Therapy with medications targeting the prostacyclin pathway is a potential risk factor for the development of symptomatic thyroid disease.

Misoprostol – Drug That Changed the Practice of Gynecology and Obstetrics with Its Off-Label Indications

Misoprostol is a synthetic analogue of prostaglandin E 1 . The drug was developed by G. D. Searle & Company in 1973 for prevention of stomach ulcers. Since 1986, it is being used for its ‘off label’ indications in obstetrics and gynecology. [1] The common indications are medical termination of pregnancy (MTP), medical management of incomplete abortion, induction of labor, cervical ripening before surgical procedures and prevention and treatment of postpartum hemorrhage [2]. Since it is inexpensive, heat stable, no drug interactions and wide range of applications in reproductive health, ‘WHO’ in 2011 has added it in the model list of essential medicines. In this article we have reviewed misoprostol its uses and recommendations in modern obstetrics and gynecology.

Uterine rupture following misoprostol improper use

Introduction: Misoprostol, a synthetic prostaglandin E1 analogue, is considered safe and is being used worldwide for second trimester pregnancy terminations, with successful results. However, complications of uterine rupture and hysterectomy have been reported, and the incidence is higher among women with prior cesarean scar. Maternal morbidity and mortality following induced abortions are directly proportional to the gestational age at termination. We report a case of a 32-year-old multipara, G3P2, with two prior low transverse cesarean sections, who experienced uterine rupture after vaginal misoprostol administration, following an illegal second trimester abortion of an undesired pregnancy of about 20 weeks’ gestation. She presented at emergency room complaining of acute lower abdominal pain and sparse vaginal hemorrhage. Fetal demise and uterine rupture were diagnosed by manual vaginal exam and ultrasound. She underwent emergency exploratory laparotomy that revealed massive hemorrhage arising from a complete and extended uterine rupture from the previous cesarean section scar. A total hysterectomy and intra-operative blood transfusion had to be performed. Her post-operative was uneventful.

Preventive and therapeutic strategies of pharmaco-correction gastropathy induced by nonsteroidal anti-inflammatory drugs

Today the problem of prevention and treatment of gastropathy associated with nonsteroidal anti-inflammatory drugs has not lost its relevance. In order to reduce the ulcerogenicity of non-steroidal anti-inflammatory drugs, it is classically accepted to supplement the therapy scheme with preparations of other pharmacological groups - antacids, alginates, M-cholinoblockers, gastrin receptor antagonists, H2-histamine blockers, proton pump inhibitors, synthetic analogues of prostaglandins or stimulators of their synthesis, reparants, gastroprotectors. Nowadays, it was suggested I was suggested the use of drugs which have pharmacological properties polyvector (vinboron, thiotriazoline et al.). Also, the scientists started of combined preparations “NSAIDs + drugs other pharmacological groups” - indotril (indomethacin + thiotriazoline) diklokor (diclofenac + quercetin) Artrotek (diclofenac sodium + misoprostol) dueksis (ibuprofen + famotidine) vimovo (naproxen + esomeprazole) aksorid (ketoprofen + omeprazole) tioaspekard (thiotriazoline + ACK) aspifat (ACK + sucralfate), Alka-Zelttser® (ACK + sodium bicarbonate), and others. The second direction is preventing and improving NSAID gastrotoxicity protrudes improving existing non-steroidal drugs - modification of gaseous molecules (NO, H2S, CO), amino acid derivatives, modulators “effector function” of afferent terminals n. vagus (amtolmetina guatsil) то pairing with nanoparticles biometals (Zn-ibuprofen, Zn-naproxen, Zn-indomethacin). (For citation: Hladkykh FV. Preventive and therapeutic strategies of pharmaco-correction gastropathy induced by nonsteroidal anti-inflammatory drugs. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):14-23. doi: 10.17816/RCF15414-23).

Does Misoprostol for Induction of Labor Increase the Risk of Uterine Rupture?

Background: Misoprostol is a synthetic prostaglandin E1 analogue which is now commonly used for induction of labor. Hyperstimulation is a complication of misoprostol that may lead to uterine rupture.Objective: To find the association between misoprostol exposure for induction of labor with uterine rupture.Methods: Case were all women who delivered in Sardjito and affiliate Hospitals from January 2007 to November 2012 with the diagnosis of uterine rupture. Controls were taken randomly from the same hospital. Chi square test and logistic regression model were used for statistical analysis.Result and Discussion: There were 53 cases of uterine rupture and 199 controls. The incidence of uterine rupture was 53 over 64,244 deliveries or 0,08%. Risk of of uterine rupture associated with misoprostol exposure was 1, 09 (CI 95% 0,52-2,2), while that of oxytocin exposure was 0,80 (CI 95% 0,35-1,85). Logistic regression analysis showed that the highest risk factor associated with uterine rupture was fetal weight > 3500 (OR 3,46; 95% CI 1,48-8,56) followed by parity (OR 2,56;95% CI 1,019-6,465) and vacuum extraction(OR 2,45;95% CI 0,94-6,39).Conclusion: There was no association between misoprostol exposure with uterine rupture. Fetal weight> 3500 gram, Parity more than 3, and vacuum extraction increased the risk of uterine rupture associated with misoprostol use.Keywords: Misoprostol, induction of labor, uterine rupture, fetal weight, parity.

A new technique in the laparoscopic resection of cornual ectopic pregnancies: a case series

Cornual ectopic pregnancies are a challenging dilemma faced in the early pregnancy setting. They are associated with high morbidity and mortality rates when compared to standard tubal ectopic pregnancies mainly due to their late presentation and significant haemorrhage and hysterectomy risk. Laparoscopic resection has been described successfully; however, the procedure can be technically very challenging and can carry significant potential risks of bleeding and conversion to laparotomy. Carboprost is a synthetic prostaglandin analogue, used widely in the management of obstetric haemorrhage, with its main mode of action being myometrial contractions. We present a series of four cases where intramyometrial carboprost injection was used successfully, prior to the laparoscopic resection of cornual ectopic pregnancies, to produce consistent and reproducible surgical benefits including prolonged myometrial contractions and subsequent reduced uterine blood flow. This results in a significant reduction in intraoperative blood loss as well as a clearer demarcation of the ectopic pregnancy and a technically easier resection.

CLINICAL AND PHARMACOLOGICAL CHARACTERISTICS OF THE USE OF REBAMIPIDE IN DISEASES OF THE GASTROINTESTINAL TRACT LITERATURE REVIEW

NSAID-induced lesions of the gastrointestinal tract gained wide spread in the recent decade. Their range includes lesion of the esophagus, syndrome of dyspepsia, gastropathy and enteropathy. Diagnosis establishment of enteropathy is complicated and became possible after introduction of the capsule endoscopy. PPI are used for treatment of gastropathy, but they are not effective for treating enteropathy. Cytoprotective prostaglandins play the key role in the development of NSAID lesions of the gastrointestinal tract. Synthetic analogues of prostaglandins of misoprostol type possess cytoprotective action, but cause a significant number of adverse events. Rebamipide, a new gastroprotective agent in Russia stimulates production of endogenous prostaglandins. This drug proved its efficacy during the clinical trials performed according to the standards of the evidence-based medicine.