Oxytocin is also available in intranasal spray form for psychiatric, endocrine and weight management use as a supplement. Intranasal oxytocin works on a different pathway than injected oxytocin, primarily along the olfactory nerve crossing theblood–brain barrier to the olfactory lobe in the brain, where dense magnocellular oxytocin neurons receive the nerve impulse quickly.
An intravenous infusion of oxytocin is used toinduce labor and to support labor in case of slow childbirth if theoxytocin challenge test fails. The physiology of labor stimulated by oxytocin administration is similar to the physiology of spontaneous labor.[11] It is associated with less tachysystole (more than five contractions in 10 minutes, averaged over a 30-minute period, which can but does not always cause fetal distress) than other induction methods and allows achievement of delivery with amniotomy to proceed faster.[12][13][needs update] Whether a high dose is better than a standard dose for labor induction is unclear. It has largely replacedergometrine as the principal agent to increase uterine tone in acutepostpartum hemorrhage. Oxytocin is also used inveterinary medicine to facilitate birth and to stimulate milk release.
Thetocolytic agentatosiban (Tractocile) acts as an antagonist of oxytocin receptors. It is registered in many countries for use in suppressing premature labor between 24 and 33 weeks of gestation. It has fewer side effects than drugs previously used for this purpose (such asritodrine,salbutamol andterbutaline).[14]
Oxytocin has not been found to be useful for improving breastfeeding success.[15]
Increased blood pressure when combined with other medications that raise blood pressure, particularly when used prior to administering epidural anesthesia[18]
Impaireduterine blood flow or excessive uterine contractions when combined with other medications that cause uterine contraction (carboprost, misoprostol)[18]
Many of these side effects are unable to be differentiated from the risks of normal labor versus oxytocin administration itself.[18][19]
Oxytocin during labour is associated with a significantly higher risk of severe postpartum hemorrhage.[20]
Excessive dosage or long-term administration (over a period of 24 hours or longer) has been known to result intetanic uterine contractions,uterine rupture, sometimes fatal.Water intoxication may be exhibited in administration through symptoms such as seizures, comas, neonatal jaundice, and potential fatality.[21] Managed fluid intake and consistent monitoring of sodium levels has been researched as crucial in the safe administration of oxytocin.[22]
The use of oxytocin during childbirth has been linked to an increased need for other medical interventions, most primarily, through the administration of anepidural anaesthetic.[23] This has been documented as creating a 'cascade effect', potentially causing detrimental impacts to the birthing process.[24][25] Oxytocin administration also, conversely, decreases the rate of cesarean sections.[26] Use of oxytocin has been found to significantly shorten labor duration.[26] Early oxytocin augmentation has also been found to increase the probability of spontaneous vaginal delivery and reduce the risk of chorioamnionitis or intrauterine infection.[27][28]
Since a landmark investigation was published inJAMA Pediatrics by researchers in 2013,[29] the potential link between oxytocin use during childbirth and increased risks ofAutism Spectrum Disorder (ASD) in children's development has been a topic of debate.[30] There is no robust evidence in support of oxytocin causing ASD or other neurodevelopmental disorders.[31]
Oxytocin was added to the Institute for Safe Medication Practices's list of High Alert Medications in Acute Care Settings in 2012.[32] The list includes medications that have a high risk for harm if administered incorrectly.[32]
During pregnancy, increased uterine motility has led to decreased heart rate, cardiac arrhythmia, seizures,brain damage, anddeath in thefetus orneonate.[17] Increased uterine motility is a hallmark of both spontaneous labor and induced labor, therefore the risks associated with uterine motility are not specific to this medication.[33]
Certain learning and memory functions are impaired by centrally administered oxytocin.[35] Also, systemic oxytocin administration can impair memory retrieval in certain aversive memory tasks.[36] However, oxytocin does seem to facilitate learning and memory specifically for social information. Healthy males administered intranasal oxytocin show improvedmemory for human faces, in particular happy faces.[37][38]
Injection: Clinical doses of oxytocin are given by injection either into a muscle or into a vein to cause contraction of the uterus.[6] Very small amounts (< 1%) do appear to enter thecentral nervous system in humans when peripherally administered.[46][better source needed] The compound has ahalf-life of typically about 3 minutes in the blood when givenintravenously. Intravenous administration requires 40 minutes to reach asteady-state concentration and achieve maximum uterine contraction response.[47]
Buccal: Oxytocin was delivered in buccal tablets, but this is not common practice any more.[48]
Nasal administration: Oxytocin is effectivelydistributed to the brain when administeredintranasally via anasal spray, after which it reliably crosses theblood–brain barrier and exhibitspsychoactive effects in humans.[50][51] No serious adverse effects with short-term application of oxytocin with 18~40 IU (36–80 mcg) have been recorded.[52] Intranasal oxytocin has a central duration of at least 2.25 hours and as long as 4 hours.[4][5]
Oral: While it was originally assumed that Oxytocin administered orally would be destroyed in thegastrointestinal tract, studies have shown that Oxytocin is transported by theimmunoglobulin RAGE (receptor for advanced glycation end products) across the intestinal epithelium and into the blood. Orally-administered Oxytocin has been shown to increaseputamen responses to facial emotions in humans.[53] Oxytocin administered orally produces different effects on human behaviour and brain function than when given intranasally, possibly due to variations in the molecular transport and binding mechanisms.
Oxytocin's uterine-contracting properties were discovered by British pharmacologistHenry Hallett Dale in 1906.[9] Oxytocin's milk ejection property was described by Ott and Scott in 1910[55] and by Schafer and Mackenzie in 1911.[56]
Oxytocin was the first polypeptide hormone to be sequenced[57] orsynthesized.[58][59] Du Vigneaud was awarded the Nobel Prize in 1955 for his work.[60]
Relationship counseling: The use of oxytocin in relationship counseling for well-being has been suggested.[72]
Post-traumatic stress disorder: It has been suggested that oxytocin may be a safer option than MDMA for the treatment of PTSD, although oxytocin has less evidence of efficacy.[73]
^abHuffmeijer R, Alink LR, Tops M, Grewen KM, Light KC, Bakermans-Kranenburg MJ, et al. (2012). "Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration".Neuro Endocrinology Letters.33 (1):21–25.PMID22467107.
^abcde"Oxytocin". The American Society of Health-System Pharmacists.Archived from the original on 20 May 2015. Retrieved1 June 2015.
^World Health Organization (2023).The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization.hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^Hofmeyr GJ, Gülmezoglu AM, et al. (The Cochrane Collaboration) (20 January 2003). "Vaginal misoprostol for cervical ripening and induction of labour".The Cochrane Database of Systematic Reviews (1). Chichester, UK: John Wiley & Sons, Ltd: CD000941.doi:10.1002/14651858.cd000941.PMID12535398.
^Wei SQ, Luo ZC, Xu H, Fraser WD (September 2009). "The effect of early oxytocin augmentation in labor: a meta-analysis".Obstetrics and Gynecology.114 (3):641–649.doi:10.1097/AOG.0b013e3181b11cb8.PMID19701046.
^Son M, Roy A, Stetson BT, Grady NT, Vanecko MC, Bond N, et al. (June 2021). "High-Dose Compared With Standard-Dose Oxytocin Regimens to Augment Labor in Nulliparous Women: A Randomized Controlled Trial".Obstetrics and Gynecology.137 (6):991–998.doi:10.1097/AOG.0000000000004399.PMID33957657.
^Gregory SG, Anthopolos R, Osgood CE, Grotegut CA, Miranda ML (October 2013). "Association of autism with induced or augmented childbirth in North Carolina Birth Record (1990-1998) and Education Research (1997-2007) databases".JAMA Pediatrics.167 (10):959–966.doi:10.1001/jamapediatrics.2013.2904.PMID23938610.
^Lønfeldt NN, Verhulst FC, Strandberg-Larsen K, Plessen KJ, Lebowitz ER (April 2019). "Assessing risk of neurodevelopmental disorders after birth with oxytocin: a systematic review and meta-analysis".Psychological Medicine.49 (6):881–890.doi:10.1017/S0033291718003021.PMID30444210.
^Drakopoulos A, Moianos D, Prifti GM, Zoidis G, Decker M (July 2022). "Opioid Ligands Addressing Unconventional Binding Sites and More Than One Opioid Receptor Subtype".ChemMedChem.17 (14): e202200169.doi:10.1002/cmdc.202200169.PMID35560796.
^Mizuguchi T, Miyano K, Yamauchi R, Yoshida Y, Takahashi H, Yamazaki A, et al. (January 2023). "The first structure-activity relationship study of oxytocin as a positive allosteric modulator for the µ opioid receptor".Peptides.159: 170901.doi:10.1016/j.peptides.2022.170901.PMID36347314.
^Seitchik J, Castillo M (December 1982). "Oxytocin augmentation of dysfunctional labor. I. Clinical data".American Journal of Obstetrics and Gynecology.144 (8):899–905.doi:10.1097/00006254-198307000-00010.PMID7148921.
^Mehta AC (1986). "Buccal and oral drugs: induction of labour".Acta Chirurgica Hungarica.27 (3):157–63.PMID3469841.
^Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 7: Neuropeptides". In Sydor A, Brown RY (eds.).Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical.ISBN978-0-07-148127-4.Oxytocin can be delivered to humans via nasal spray following which it crosses the blood–brain barrier. ... In a double-blind experiment, oxytocin spray increased trusting behavior compared to a placebo spray in a monetary game with real money at stake.
^du Vigneaud V, Ressler C, Swan JM, Roberts CW, Katsoyannis PG, Gordon S (1953). "The synthesis of an octapeptide amide with the hormonal activity of oxytocin".J. Am. Chem. Soc.75 (19):4879–80.Bibcode:1953JAChS..75.4879V.doi:10.1021/ja01115a553.
^Bartz JA, Hollander E (2008). "Oxytocin and experimental therapeutics in autism spectrum disorders".Advances in Vasopressin and Oxytocin – from Genes to Behaviour to Disease. Progress in Brain Research. Vol. 170. Elsevier. pp. 451–62.doi:10.1016/S0079-6123(08)00435-4.ISBN978-0-444-53201-5.PMID18655901.
