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 the brain blood barrier to the olfactory lobe in the brain, where dense magnocellular oxytocin neurons receive the dose application.
An intravenous infusion of oxytocin is used to induce labor and to support labor in case of slow childbirth if the oxytocin challenge test fails. Whether a high dose is better than a standard dose for labor induction is unclear. It has largely replaced ergometrine as the principal agent to increase uterine tone in acute postpartum hemorrhage. Oxytocin is also used in veterinary medicine to facilitate birth and to stimulate milk release.
The tocolytic agent atosiban (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 as ritodrine, salbutamol and terbutaline).[11]
Oxytocin has not been found to be useful for improving breastfeeding success.[12]
Contraindications
Oxytocin injection (synthetic) is contraindicated in any of these conditions:[13]
Excessive dosage or long-term administration (over a period of 24 hours or longer) has been known to result in tetanic uterine contractions, uterine rupture, postpartum hemorrhage, sometimes fatal. Water intoxication may be exhibited in administration through symptoms such as seizures, comas, neonatal jaundice, and potential fatality.[15] Managed fluids intake and consistent monitoring of sodium levels has been researched as crucial in the safe administration of oxytocin.[16]
The use of oxytocin during childbirth has been linked to an increased need for other medical interventions, most primarily, through the administration of an epidural anaesthetic.[17] This has been documented as creating a 'cascade effect', potentially causing detrimental impacts to the birthing process.[18][19]
Since a landmark investigation was published in JAMA Pediatrics by researchers in 2013,[20] the potential link between oxytocin use during childbirth and increased risks of Autism Spectrum Disorder (ASD) in children's development has been a topic of debate.[21]
Oxytocin was added to the Institute for Safe Medication Practices's list of High Alert Medications in Acute Care Settings in 2012.[22] The list includes medications that have a high risk for harm if administered incorrectly.[22]
During pregnancy, increased uterine motility has led to decreased heart rate, cardiac arrhythmia, seizures, brain damage, and death in the fetus or neonate.[14]
Certain learning and memory functions are impaired by centrally administered oxytocin.[24] Also, systemic oxytocin administration can impair memory retrieval in certain aversive memory tasks.[25] However, oxytocin does seem to facilitate learning and memory specifically for social information. Healthy males administered intranasal oxytocin show improved memory for human faces, in particular happy faces.[26][27]
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 the central nervous system in humans when peripherally administered.[28][better source needed] The compound has a half-life of typically about 3 minutes in the blood when given intravenously. Intravenous administration requires 40 minutes to reach a steady-state concentration and achieve maximum uterine contraction response.[29]
Buccal: Oxytocin was delivered in buccal tablets, but this is not common practice any more.[30]
Nasal administration: Oxytocin is effectively distributed to the brain when administered intranasally via a nasal spray, after which it reliably crosses the blood–brain barrier and exhibits psychoactive effects in humans.[32][33] No serious adverse effects with short-term application of oxytocin with 18~40 IU (36–80 mcg) have been recorded.[34] 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 the gastrointestinal tract, studies have shown that Oxytocin is transported by the immunoglobulin RAGE (receptor for advanced glycation end products) across the intestinal epithelium and into the blood. Orally-administered Oxytocin has been shown to increase putamen responses to facial emotions in humans.[35] 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 pharmacologist Henry Hallett Dale in 1906.[9] Oxytocin's milk ejection property was described by Ott and Scott in 1910[37] and by Schafer and Mackenzie in 1911.[38]
Oxytocin was the first polypeptide hormone to be sequenced[39] or synthesized.[40][41] Du Vigneaud was awarded the Nobel Prize in 1955 for his work.[42]
Etymology
The word oxytocin was coined from the term oxytocic. Greek ὀξύς, oxys, and τόκος, tokos, meaning "quick birth".
^ 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.
^ abcdefghi"Oxytocin". The American Society of Health-System Pharmacists. Archived from the original on 20 May 2015. Retrieved 1 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.
^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.
^Oberg AS, D'Onofrio BM, Rickert ME, Hernandez-Diaz S, Ecker JL, Almqvist C, et al. (September 2016). "Association of Labor Induction With Offspring Risk of Autism Spectrum Disorders". JAMA Pediatrics. 170 (9): e160965. doi:10.1001/jamapediatrics.2016.0965. hdl:10616/45629. PMID27454803.
^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. doi:10.1021/ja01115a553.
^du Vigneaud V, Ressler C, Swan JM, Roberts CW, Katsoyannis PG (June 1954). "The synthesis of oxytocin". J. Am. Chem. Soc. 76 (12): 3115–21. doi:10.1021/ja01641a004.
^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. pp. 451–62. doi:10.1016/S0079-6123(08)00435-4. ISBN978-0-444-53201-5. PMID18655901.
