Misoprostol

Can the Induction of Labor with Misoprostol Increase Maternal Blood Loss?[Pubmed:28320031]

Rev Bras Ginecol Obstet. 2017 Feb;39(2):53-59.

Purpose To evaluate blood loss during Misoprostol-induced vaginal births and during cesarean sections after attempted Misoprostol induction. Methods We conducted a prospective observational study in 101 pregnant women indicated for labor induction; pre- and postpartum hemoglobin levels were measured to estimate blood loss during delivery. Labor was induced by administering 25 microg vaginal Misoprostol every 6 hours (with a maximum of 6 doses). The control group included 30 patients who spontaneously entered labor, and 30 patients who underwent elective cesarean section. Pre- and postpartum hemoglobin levels were evaluated using the analysis of variance for repeated measurements, showing the effects of time (pre- and postpartum) and of the group (with and without Misoprostol administration). Results There were significant differences between pre- and postpartum hemoglobin levels (p < 0.0001) with regard to Misoprostol-induced vaginal deliveries (1.6 +/- 1.4 mg/dL), non-induced vaginal deliveries (1.4 +/- 1.0 mg/dL), cesarean sections after attempted Misoprostol induction (1.5 +/- 1.0 mg/dL), and elective cesarean deliveries (1.8 +/- 1.1 mg/dL). However, the differences were proportional between the groups with and without Misoprostol administration, for both cesarean (p = 0.6845) and vaginal deliveries (p = 0.2694). Conclusions Labor induction using Misoprostol did not affect blood loss during delivery.

Community-based misoprostol for the prevention of post-partum haemorrhage: A narrative review of the evidence base, challenges and scale-up.[Pubmed:28357885]

Glob Public Health. 2018 Aug;13(8):1081-1097.

Achieving Sustainable Development Goal targets for 2030 will require persistent investment and creativity in improving access to quality health services, including skilled attendance at birth and access to emergency obstetric care. Community-based Misoprostol has been extensively studied and recently endorsed by the WHO for the prevention of post-partum haemorrhage. There remains little consolidated information about experience with implementation and scale-up to date. This narrative review of the literature aimed to identify the political processes leading to WHO endorsement of Misoprostol for the prevention of post-partum haemorrhage and describe ongoing challenges to the uptake and scale-up at both policy and community levels. We review the peer-reviewed and grey literature on expansion and scale-up and present the issues central to moving forward.

Misoprostol use for second-trimester termination of pregnancy among women with one or more previous cesarean deliveries.[Pubmed:28378361]

Int J Gynaecol Obstet. 2017 Jul;138(1):23-27.

OBJECTIVE: To establish the safety and efficacy of Misoprostol for second-trimester termination of pregnancy among women with one or more previous cesarean deliveries. METHODS: In a retrospective study, data were reviewed from women attending a reproductive health clinic in Bloemfontein, South Africa, for second-trimester termination between 2010 and 2013. The study group, comprising women with one or more previous cesareans, was compared with a control group, comprising women with no previous cesarean or uterine scarring. Procedure-specific information was compared, including Misoprostol use, termination duration, need for other methods (e.g. oxytocin), placenta delivery, termination outcome, and bleeding. RESULTS: The study group comprised 268 women: 231 (86.2%) with one and 37 (13.8%) with two previous cesareans. The control group comprised 266 women. Incomplete abortion was recorded in 223 (85.4%) of 261 women in the study group and 213 (80.4%) of 265 in the control group. The number of women with retained placenta was higher in the study than in the control group (158/261 [60.5%] vs 146/265 [55.1%]; P<0.001). Severe bleeding was observed only in the control group (7/266 [2.6%]). No uterine rupture was observed. CONCLUSION: Misoprostol was safe for second-trimester termination among women with previous cesareans; however, the efficacy of the local regimen was reduced owing to high placental retention.

Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells.[Pubmed:9313928]

Br J Pharmacol. 1997 Sep;122(2):217-24.

1. Eight types and subtypes of the mouse prostanoid receptor, the prostaglandin D (DP) receptor, the prostaglandin F (FP) receptor, the prostaglandin I (IP) receptor, the thromboxane A (TP) receptor and the EP1, EP2, EP3 and EP4 subtypes of the prostaglandin E receptor, were stably expressed in Chinese hamster ovary cells. Their ligand binding characteristics were examined with thirty two prostanoids and their analogues by determining the Ki values from the displacement curves of radioligand binding to the respective receptors. 2. The DP, IP and TP receptors showed high ligand binding specificity and only bound their own putative ligands with high affinity such as PGD2, BW245C and BW868C for DP, cicaprost, iloprost and isocabacyclin for IP, and S-145, I-BOP and GR 32191 for TP. 3. The FP receptor bound PGF2 alpha and fluprostenol with Ki values of 3-4 nM. In addition, PGD2, 17-phenyl-PGE2, STA2, I-BOP, PGE2 and M&B-28767 bound to this receptor with Ki values less than 100 nM. 4. The EP1 receptor bound 17-phenyl-PGE2, sulprostone and iloprost in addition to PGE2 and PGE1, with Ki values of 14-36 nM. 16,16-dimethyl-PGE2 and two putative EP1 antagonists, AH6809 and SC-19220, did not show any significant binding to this receptor. M&B-28767, a putative EP3 agonist, and Misoprostol, a putative EP2/EP3 agonist, also bound to this receptor with Ki values of 120 nM. 5. The EP2 and EP4 receptors showed similar binding profiles. They bound 16,16-dimethyl PGE2 and 11-deoxy-PGE1 in addition to PGE2 and PGE1. The two receptors were discriminated by butaprost, AH-13205 and AH-6809 that bound to the EP2 receptor but not to the EP4 receptor, and by 1-OH-PGE1 that bound to the EP4 but not to the EP2 receptor. 6. The EP3 receptor showed the broadest binding profile, and bound sulprostone, M&B-28767, GR63799X, 11-deoxy-PGE1, 16,16-dimethyl-PGE2 and 17-phenyl-PGE2, in addition to PGE2 and PGE1, with Ki values of 0.6-3.7 nM. In addition, three IP ligands, iloprost, carbacyclin and isocarbacyclin, and one TP ligand, STA2, bound to this receptor with Ki values comparable to the Ki values of these compounds for the IP and TP receptors, respectively. 7. 8-Epi-PGF2 alpha showed only weak binding to the IP, TP, FP, EP2 and EP3 receptor at 10 microM concentration.

Characterization of dilator prostanoid receptors in the fetal rabbit ductus arteriosus.[Pubmed:7965740]

J Pharmacol Exp Ther. 1994 Oct;271(1):390-6.

The purpose of this study was to determine which receptors mediate the dilator effects of prostaglandins (PGs) on the ductus arteriosus of the fetal rabbit. Isolated rings of the vessel from fetal New Zealand White rabbits were precontracted with indomethacin (1 microM) and potassium (25 mM) in 100 to 110 mmHg oxygen, and the dilator effects of a range of synthetic prostanoids were quantified by cumulative relaxant concentration-effect curves. The potencies of agonists were quantified with reference to PGE2 by the equieffective molar ratio (EMR): EC50 test agonist/EC50 PGE2. The effects on these responses of available antagonists were also studied. None of a range of synthetic prostanoids with selective agonism of EP1, EP2 or EP3 receptors was as potent as PGE2. The rank order of potency was as follows: PGE2 (EC50 = 0.36 nM [95% confidence intervals [CI] = 0.32-0.41, n = 44], EMR = unity) >> Misoprostol (EMR 145, 95% CI 73-217) > [1R-[1 alpha (Z),2 beta (R*),3 alpha]]-4-(benzoyl-amino)phenyl 7-[3 hydroxy-2(2-hydroxy-3-phenoxypropoxy)-5- oxocyclopentyl]-4-heptenoate, single enantiomer (GR 63799K) (EMR 685, 95% CI 427-944) >> ((+/-)-trans-2-[4[(1-hydroxphenyl) phenyl]-5-oxocylopentaneheptanoic acid (AH13205) (EMR > 100,000) > or = sulprostone (EMR > 10,000) > or = 0. The EP1 antagonists, 6-isopropoxy-9-oxoxanthine-2-carboxylic acid (AH6809) (10 microM) and 8-clorodi-benz[b,f][1,4]oxazepine-10 (11H)-carboxylic acid, 2-acetylhydrazide (SC19220) (30 microM), had no significant effect on the sensitivity of the ductus to PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial.[Pubmed:2904006]

Lancet. 1988 Dec 3;2(8623):1277-80.

A double-blind, placebo-controlled study was carried out to see whether the synthetic E prostaglandin, Misoprostol, would prevent gastric ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). 420 patients with osteoarthritis and NSAID-associated abdominal pain were studied; they were receiving ibuprofen, piroxicam, or naproxen. Endoscopy was done at entry and after 1, 2, and 3 months of continuous treatment with 100 micrograms or 200 micrograms Misoprostol or placebo, given four times daily with meals and at bedtime, concurrently with the NSAID. Abdominal pain was rated independently by patients and physicians. A treatment failure was defined as development of a gastric ulcer. Gastric ulcers (0.3 cm in diameter or greater) occurred less frequently (p less than 0.001) in both Misoprostol treatment groups (5.6% 100 micrograms and 1.4% 200 micrograms) than in the placebo group (21.7%). The significant difference in ulcer formation between the placebo and the Misoprostol treatment groups remained when comparisons were restricted to ulcers greater than 0.5 cm in diameter (12.3% placebo, 4.2% 100 micrograms Misoprostol, and 0.7% 200 micrograms Misoprostol). Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to Misoprostol. These results provide the first clear indication that NSAID-induced ulcers are preventable.