Oxytocin Oxytocin is a peptide hormone produced in the
hypothalamus that plays an important role in many physiological functions. These functions include, enhancing mood and social relationships, promotion of maternal behaviors and stimulations of uterine contractions, among others roles. Uterine muscle contractions are induced via a
G-protein pathway stemming from the
oxytocin receptor (OXTR), the
binding and
activation site of oxytocin. When oxytocin binds to its associated receptors in the uterus, a cascade is initiated that results in an increase in calcium and subsequently an increase in muscle contractions. The release of oxytocin helps to facilitate stronger contractions during labor to aid in delivery of the fetus. Additionally, during pregnancy, the uterine muscles have an increased concentration of oxytocin receptors, leading to an increased response to oxytocin as well.
Role in postpartum hemorrhage The most common cause of postpartum hemorrhage is a loss of muscle tone in the uterus. Normally, the uterus will contract to constrict blood vessels and decrease the flow of blood to prevent bleeding out. However, if there is a loss of muscle tone, see
uterine atony, there is an increased risk of bleeding. Oxytocin is the first-line pharmacological step to help prevent PPH and treat PPH. It is approved for use in 23 various countries around the world (not approved in United States). In Canadian and German guidelines, carbetocin is recommended as a first-line therapy treatment for post-partum hemorrhaging with notable efficacy when used with cesarean section deliveries. Carbetocin has been shown to be more effective than oxytocin in preventing postpartum hemorrhaging as well. Common side effects of carbetocin include vomiting, fever, and hypertension- similar side effect profile to that of oxytocin. Prostaglandins (PGs) have been attributed to partaking in the mechanisms of uterine activity during labor. The presence of PGs and PG receptors increases throughout the pregnancy, and PGs increase expression of oxytocin receptors as well. Along with the increase in oxytocin receptors to facilitate labor, PGs also increase the intracellular concentration of calcium.
Misoprostol Misoprostol is an analogue of PGE1 and is a popular choice for PPH prophylaxis and treatment. Misoprostol is easily administered, considered safe, and is low-cost. The routes of administration include
sublingual, oral, vaginal, and rectal, with greatest efficacy from sublingual and vaginal administration. Vaginally administered misoprostol had improved outcomes of inducing labor within twenty-four hours compared to oxytocin, but was associated with
uterine hyperstimulation. Misoprostol is an agonist of EP1 and EP3 receptors, and can cause a greater stimulation at lower concentrations. At higher concentrations, the medication can suppress contractions.
Other prostaglandin analogues •
Alprostadil is commonly known as PGE1 and is a naturally occurring prostaglandin and vasodilator. Alprostadil has not been added to the guidelines to treat PPH. The medication is not indicated for inducing labor, PPH, nor women, but for
erectile dysfunction. •
Dinoprost is also known as PGF2α and is a naturally occurring prostaglandin which causes contraction via PGF receptors. Dinoprost was discontinued in 2015. Methylergonovine is intravenously administered with onset and duration of action similar to that of ergometrine. Its most common side effect is hypertension. Methylergonovine is recommended as a second-line therapy in treating postpartum hemorrhaging due to uterine atony according to both the
American College of Obstetricians and Gynecologists (ACOG) and the
Royal College of Obstetrics and Gynecology. In 2012, ACOG published a warning regarding use of methylergonovine's usage in people with hypertension where it was suspected to have caused
myocardial infarction and ischemia in those individuals. == References ==