oxytocin
Regulatory sources consulted
Approved indications
- Medically indicated induction or augmentation of labor, adjunctive treatment of incomplete/inevitable/missed abortion, and prevention or treatment of postpartum uterine atony and hemorrhage.
Contraindications
Absolute
- Mechanical obstruction, fetal distress, uterine hypertonia, or any condition contraindicating vaginal delivery; placenta or vasa previa, placental abruption, cord prolapse, overdistension, or major uterine scar; administration within 6 hours after vaginal prostaglandins.
Clinical warnings
- Major warning · Hospital use with continuous monitoring of contractions and fetal heart rate. Stop immediately for uterine hyperactivity or fetal distress; overdose may cause uterine rupture, fetal asphyxia, or death. — CIMA/AEMPS, ficha técnica 83282
- Major warning · Prolonged infusion with fluids may cause water intoxication and hyponatremia. Use cautiously with heart disease and QT risk; avoid rapid IV bolus because of hypotension and reflex tachycardia. — CIMA/AEMPS, ficha técnica 83282
- Major warning · Do not use for prolonged periods in oxytocin-resistant uterine inertia, severe preeclampsia, or severe cardiovascular disease. — CIMA/AEMPS, ficha técnica 83282
Drug interactions
- HighProstaglandins and analogs
Mechanism: Uterotonic effects are mutually potentiated.
Recommendation: Do not start oxytocin until 6 hours after vaginal prostaglandins.
CIMA/AEMPS, ficha técnica 83282https://cima.aemps.es/cima/dochtml/ft/83282/FT_83282.html
- HighQT-prolonging drugs, inhaled anesthetics, or vasoconstrictors
Mechanism: They may increase arrhythmia, reduce uterotonic effect, or potentiate the pressor response.
Recommendation: Monitor ECG, blood pressure, and uterine response; avoid high-risk combinations.
CIMA/AEMPS, ficha técnica 83282https://cima.aemps.es/cima/dochtml/ft/83282/FT_83282.html
Adverse events
Common (≥1%)
Nausea or vomiting · Headache · Tachycardia or bradycardia · Abdominal pain or uterine contractions
Rare but serious
Uterine rupture · Fetal distress, asphyxia, or death · Disseminated intravascular coagulation · Water intoxication or severe hyponatremia · Anaphylaxis
Pregnancy and lactation
Use during pregnancy only for strict obstetric indications. Small amounts enter milk, but gastrointestinal inactivation makes harm to the infant unlikely.
Recent literature (PubMed)
Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and paraventricular nucleus of the hypothalamus and released from the posterior pituitary lobe into the circulation. Oxytocin is released in pulses with increasing frequency and amplitude in the first and second stages of labor, with a few pulses released in the third stage of labor. During labor, the fetus exerts pressure on the cervix of the uterus, which activates a feedforward reflex-the Ferguson reflex-which releases oxytocin. When myometrial contractions activate sympathetic nerves, it decreases oxytocin release. When oxytocin binds to specific myometrial oxytocin receptors, it induces myometrial contractions. High levels of circulating estrogen at term make the receptors more sensitive. In addition, oxytocin stimulates prostaglandin synthesis and release in the decidua and chorioamniotic membranes by activating a specific type of oxytocin receptor. Prostaglandins contribute to cervical ripening and uterine contractility in labor. The oxytocin system in the brain has been implicated in decreasing maternal levels of fear, pain, and stress, and oxytocin release and function during labor are stimulated by a social support. Moreover, studies suggest, but have not yet proven, that labor may be associated with long-term, behavioral and physiological adaptations in the mother and infant, possibly involving epigenetic modulation of oxytocin production and release and the oxytocin receptor. In addition, infusions of synthetic oxytocin are used to induce and augment labor. Oxytocin may be administered according to different dose regimens at increasing rates from 1 to 3 mIU/min to a maximal rate of 36 mIU/min at 15- to 40-minute intervals. The total amount of synthetic oxytocin given during labor can be 5 to 10 IU, but lower and higher amounts of oxytocin may also be given. High-dose infusions of oxytocin may shorten
Oxytocin is a peptide hormone that plays a key role in regulating the female reproductive system, including during labor and lactation. It is produced primarily in the hypothalamus and secreted by the posterior pituitary gland. Oxytocin can also be administered as a medication to initiate or augment uterine contractions. To study the effectiveness and safety of oxytocin, previous studies have randomized patients to low- and high-dose oxytocin infusion protocols either alone or as part of an active management of labor strategy along with other interventions. These randomized trials demonstrated that active management of labor and high-dose oxytocin regimens can shorten the length of labor and reduce the incidence of clinical chorioamnionitis. The safety of high-dose oxytocin regimens is also supported by no associated differences in fetal heart rate abnormalities, postpartum hemorrhage, low Apgar scores, neonatal intensive care unit admissions, and umbilical artery acidemia. Most studies reported no differences in the cesarean delivery rates with active management of labor or high-dose oxytocin regimens, thereby further validating its safety. Oxytocin does not have a predictable dose response, thus the pharmacologic effects and the amplitude and frequency of uterine contractions are used as physiological parameters for oxytocin infusion titration to achieve adequate contractions at appropriate intervals. Used in error, oxytocin can cause patient harm, highlighting the importance of precise administration using infusion pumps, institutional safety checklists, and trained nursing staff to closely monitor uterine activity and fetal heart rate changes. In this review, we summarize the physiology, pharmacology, infusion regimens, and associated risks of oxytocin.
There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD. We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses. We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin
Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide, with uterine atony estimated to account for 70% to 80% of cases, thereby remaining the single most common cause. Pharmacotherapy remains the first-line preventative therapy for postpartum hemorrhage. These therapies may be single (oxytocin, carbetocin, methylergonovine, ergometrine, misoprostol, prostaglandin analogs, or tranexamic acid) or combination therapies, acting in an additive, infra-additive, or synergistic fashion to prevent postpartum hemorrhage. Evidence is strong for the use of oxytocin, the first-line uterotonic agent in the United States for prevention of postpartum hemorrhage. Although carbetocin, a long-acting analog of oxytocin, is not yet available for use in the United States, it is likely the most effective single pharmacologic therapy for prevention of postpartum hemorrhage and need for additional uterotonics. Use of second-line uterotonics such as methylergonovine, misoprostol, and carboprost in combination with oxytocin has an additive or synergistic effect and a greater risk reduction for postpartum hemorrhage prevention compared with oxytocin alone. Therefore, combined therapy rather than oxytocin alone should be advised for preventing postpartum hemorrhage. Tranexamic acid has been found to be both effective and safe for decreasing maternal mortality in women with postpartum hemorrhage, and prophylactic use of tranexamic acid may decrease the need for packed red blood cell transfusions and/or uterotonics. The WOMAN-2 Trial, designed to assess if tranexamic acid prevents postpartum hemorrhage in women with moderate to severe anemia undergoing vaginal delivery, is currently recruiting participants. The additive, infra-additive, or synergistic action of oxytocin in combination with other second-line therapies deserves further study.
Oxytocin and vasopressin are peptide hormones secreted from the pituitary that are well known for their peripheral endocrine effects on childbirth/nursing and blood pressure/urine concentration, respectively. However, both peptides are also released in the brain, where they modulate several aspects of social behaviors. Oxytocin promotes maternal nurturing and bonding, enhances social reward, and increases the salience of social stimuli. Vasopressin modulates social communication, social investigation, territorial behavior, and aggression, predominantly in males. Both peptides facilitate social memory and pair bonding behaviors in monogamous species. Here we review the latest research delineating the neural circuitry of the brain oxytocin and vasopressin systems and summarize recent investigations into the circuit-based mechanisms modulating social behaviors. We highlight research using modern molecular genetic technologies to map, monitor activity of, or manipulate neuropeptide circuits. Species diversity in oxytocin and vasopressin effects on social behaviors are also discussed. We conclude with a discussion of the translational implications of oxytocin and vasopressin for improving social functioning in disorders with social impairments, such as autism spectrum disorder.