Oxytocin (medication) explained

Watchedfields:changed
Verifiedrevid:691721176
Width:250
Tradename:Pitocin, Syntocinon, Viatocinon, others
Dailymedid:Oxytocin
Pregnancy Au:A
Routes Of Administration:Intranasal, intravenous, intramuscular
Atc Prefix:H01
Atc Suffix:BB02
Legal Uk:POM
Legal Uk Comment:[1]
Legal Us:Rx-only
Legal Us Comment:[2] [3]
Metabolism:Liver and elsewhere (via oxytocinases)
Elimination Half-Life:1–6 min (IV)
~2 h (intranasal)
Excretion:Bile duct and kidney
Cas Number:50-56-6
Pubchem:439302
Iuphar Ligand:2174
Drugbank:DB00107
Chemspiderid:388434
Unii:1JQS135EYN
Kegg:D00089
Chebi:7872
Chembl:395429
Iupac Name:1-(carbonyl)-L-prolyl-L-leucylglycinamide
C:43
H:66
N:12
O:12
S:2
Smiles:CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H](N)CSSC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O
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Stdinchikey:XNOPRXBHLZRZKH-DSZYJQQASA-N

Synthetic oxytocin, sold under the brand name Pitocin among others, is a medication made from the peptide oxytocin.[4] As a medication, it is used to cause contraction of the uterus to start labor, increase the speed of labor, and to stop bleeding following delivery. For this purpose, it is given by injection either into a muscle or into a vein.[5]

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 blood–brain barrier to the olfactory lobe in the brain, where dense magnocellular oxytocin neurons receive the dose application.

The use of synthetic oxytocin as an injectable medication for inducing childbirth can result in excessive contraction of the uterus that can risk the health of the baby.[5] Common side effects in the mother include nausea and a slow heart rate.[5] Serious side effects include rupture of the uterus and with excessive dose, water intoxication.[5] Allergic reactions including anaphylaxis may also occur.[5]

The natural occurrence of oxytocin was discovered in 1906.[6] It is on the World Health Organization's List of Essential Medicines.[7]

Medical uses

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).[8]

Oxytocin has not been found to be useful for improving breastfeeding success.[9]

Contraindications

Oxytocin injection (synthetic) is contraindicated in any of these conditions:[10]

Side effects

Oxytocin is relatively safe when used at recommended doses, and side effects are uncommon.[11] These maternal events have been reported:[11]

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.[12] Managed fluids intake and consistent monitoring of sodium levels has been researched as crucial in the safe administration of oxytocin.[13]

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.[14] This has been documented as creating a 'cascade effect', potentially causing detrimental impacts to the birthing process.[15] [16]

Since a landmark investigation was published in JAMA Pediatrics by researchers in 2013,[17] 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.[18]

Oxytocin was added to the Institute for Safe Medication Practices's list of High Alert Medications in Acute Care Settings in 2012.[19] The list includes medications that have a high risk for harm if administered incorrectly.

During pregnancy, increased uterine motility has led to decreased heart rate, cardiac arrhythmia, seizures, brain damage, and death in the fetus or neonate.[11]

Use is linked to an increased risk of postpartum depression in the mother.[20]

Certain learning and memory functions are impaired by centrally administered oxytocin.[21] Also, systemic oxytocin administration can impair memory retrieval in certain aversive memory tasks.[22] 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.[23] [24]

Pharmacokinetics

Routes of administration

One IU of oxytocin is the equivalent of about 2 μg or mcg of pure peptide.

Chemistry

Peptide analogues of oxytocin with similar actions, for example carbetocin (Duratocin) and demoxytocin (Sandopart), have been developed and marketed for medical use.[35] In addition, small-molecule oxytocin receptor agonists, like TC OT 39, WAY-267464, and LIT-001 have been developed and studied. However, lack of selectivity over vasopressin receptors has so far limited the potential usefulness of small-molecule oxytocin receptor agonists.

History

Oxytocin's uterine-contracting properties were discovered by British pharmacologist Henry Hallett Dale in 1906.[36] 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".

Society and culture

Counterfeits

In African countries, some oxytocin products were found to be counterfeit medications.[43] [44]

Other uses

The trust-inducing property of oxytocin might help those with social anxiety and depression,[45] anxiety, fear, and social dysfunctions, such as generalized anxiety disorder, post-traumatic stress disorder, and social anxiety disorder, as well as autism and schizophrenia, among others.[46] [47] However, in one meta-analysis only autism spectrum disorder showed a significant combined effect size.[48]

People using oxytocin show improved recognition for positive social cues over threatening social cues[49] [50] and improved recognition of fear.[51]

See also

Notes and References

  1. Web site: Syntocinon 10 IU/ml Concentrate for Solution for Infusion . (emc) . 25 October 2023 . 14 January 2024.
  2. Web site: Pitocin- oxytocin injection . DailyMed . 10 January 2008 . 14 January 2024.
  3. Web site: Oxytocin injection, solution . DailyMed . 16 October 2023 . 14 January 2024.
  4. Book: The Oxford Handbook of Prosocial Behavior . 2015 . Oxford University Press . 978-0-19-539981-3 . 354 . live . https://web.archive.org/web/20170801001244/https://books.google.ca/books?id=EfzOBwAAQBAJ&pg=PA354 . 1 August 2017 .
  5. Web site: Oxytocin . The American Society of Health-System Pharmacists . 1 June 2015 . live . https://web.archive.org/web/20150520014256/http://www.drugs.com/monograph/oxytocin.html . 20 May 2015 .
  6. Book: Hurlemann R, Grinevich V . Behavioral Pharmacology of Neuropeptides: Oxytocin . 2018 . Springer . 978-3-319-63739-6 . 37 . en.
  7. Book: ((World Health Organization)) . The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) . 2023 . 10665/371090 . World Health Organization . World Health Organization . Geneva . WHO/MHP/HPS/EML/2023.02 . free .
  8. Budden A, Chen LJ, Henry A . High-dose versus low-dose oxytocin infusion regimens for induction of labour at term . The Cochrane Database of Systematic Reviews . 10 . 10 . CD009701 . 9 October 2014 . 25300173 . 10.1002/14651858.CD009701.pub2 . 8932234 .
  9. Web site: Oxytocin use while Breastfeeding . Drugs.com . live . https://web.archive.org/web/20161215130642/https://www.drugs.com/breastfeeding/oxytocin.html . 15 December 2016 .
  10. Web site: Oxytocin - FDA prescribing information, side effects and uses . 16 December 2016 . live . https://web.archive.org/web/20161221012452/https://www.drugs.com/pro/oxytocin.html . 21 December 2016 .
  11. Web site: Pitocin (drug label for professionals) . WebMD . Rx List . 9 September 2010 . live . https://web.archive.org/web/20110415062355/http://www.rxlist.com/pitocin-drug.htm . 15 April 2011 .
  12. D'Souza SW, Lieberman B, Cadman J, Richards B . Oxytocin induction of labour: hyponatraemia and neonatal jaundice . European Journal of Obstetrics, Gynecology, and Reproductive Biology . 22 . 5–6 . 309–317 . September 1986 . 3770280 . 10.1016/0028-2243(86)90119-x .
  13. Emre U, Kadıoğlu G, Ünal A, Atasoy HT . Case report: hyponatremia and generalized convulsion after intravenous oxytocin infusion. . Journal of the Turkish-German Gynecological Association . March 2009 . 10 . 1 . 47–48 .
  14. Hidalgo-Lopezosa P, Hidalgo-Maestre M, Rodríguez-Borrego MA . Labor stimulation with oxytocin: effects on obstetrical and neonatal outcomes . Revista Latino-Americana de Enfermagem . 24 . e2744 . 2016 . 27463109 . 4982443 . 10.1590/1518-8345.0765.2744 .
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  17. Gregory SG, Anthopolos R, Osgood CE, Grotegut CA, Miranda ML . 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 . October 2013 . 23938610 . 10.1001/jamapediatrics.2013.2904 .
  18. Oberg AS, D'Onofrio BM, Rickert ME, Hernandez-Diaz S, Ecker JL, Almqvist C, Larsson H, Lichtenstein P, Bateman BT . Association of Labor Induction With Offspring Risk of Autism Spectrum Disorders . JAMA Pediatrics . 170 . 9 . e160965 . September 2016 . 27454803 . 10.1001/jamapediatrics.2016.0965 . 5297393 . 10616/45629 . free .
  19. Web site: High-Alert Medications in Acute Care Settings. Institute For Safe Medication Practices. 16 November 2017 . en. 6 May 2019.
  20. Kroll-Desrosiers AR, Nephew BC, Babb JA, Guilarte-Walker Y, Moore Simas TA, Deligiannidis KM . Association of peripartum synthetic oxytocin administration and depressive and anxiety disorders within the first postpartum year . Depression and Anxiety . 34 . 2 . 137–146 . February 2017 . 28133901 . 5310833 . 10.1002/da.22599 .
  21. Gimpl G, Fahrenholz F . The oxytocin receptor system: structure, function, and regulation . Physiological Reviews . 81 . 2 . 629–83 . April 2001 . 11274341 . 10.1152/physrev.2001.81.2.629. 13265083 .
  22. de Oliveira LF, Camboim C, Diehl F, Consiglio AR, Quillfeldt JA . Glucocorticoid-mediated effects of systemic oxytocin upon memory retrieval . Neurobiology of Learning and Memory . 87 . 1 . 67–71 . January 2007 . 16997585 . 10.1016/j.nlm.2006.05.006 . 25371427 .
  23. Guastella AJ, Mitchell PB, Mathews F . Oxytocin enhances the encoding of positive social memories in humans . Biological Psychiatry . 64 . 3 . 256–58 . August 2008 . 18343353 . 10.1016/j.biopsych.2008.02.008 . 38681820 .
  24. Rimmele U, Hediger K, Heinrichs M, Klaver P . Oxytocin makes a face in memory familiar . The Journal of Neuroscience . 29 . 1 . 38–42 . January 2009 . 19129382 . 6664913 . 10.1523/JNEUROSCI.4260-08.2009 .
  25. Baribeau DA, Anagnostou E . Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits . Frontiers in Neuroscience . 9 . 335 . 2015 . 26441508 . 4585313 . 10.3389/fnins.2015.00335 . free .
  26. Seitchik J, Castillo M . Oxytocin augmentation of dysfunctional labor. I. Clinical data . American Journal of Obstetrics and Gynecology . 144 . 8 . 899–905 . December 1982 . 7148921 . 10.1097/00006254-198307000-00010 .
  27. Mehta AC . Buccal and oral drugs: induction of labour . Acta Chirurgica Hungarica . 27 . 3 . 157–63 . 1986 . 3469841 .
  28. De Groot AN, Vree TB, Hekster YA, Pesman GJ, Sweep FC, Van Dongen PJ, Van Roosmalen J . Bioavailability and pharmacokinetics of sublingual oxytocin in male volunteers . The Journal of Pharmacy and Pharmacology . 47 . 7 . 571–75 . 1995 . 8568623 . 10.1111/j.2042-7158.1995.tb06716.x . 2066/21581 . 8615529 .
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  30. McGregor IS, Callaghan PD, Hunt GE . From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use? . British Journal of Pharmacology . 154 . 2 . 358–68 . May 2008 . 18475254 . 2442436 . 10.1038/bjp.2008.132 . Recent studies also highlight remarkable anxiolytic and prosocial effects of intranasally administered OT in humans, including increased 'trust', decreased amygdala activation towards fear-inducing stimuli, improved recognition of social cues and increased gaze directed towards the eye regions of others (Kirsch et al., 2005; Kosfeld et al., 2005; Domes et al., 2006; Guastella et al., 2008). .
  31. Lee SY, Lee AR, Hwangbo R, Han J, Hong M, Bahn GH . Is Oxytocin Application for Autism Spectrum Disorder Evidence-Based? . Experimental Neurobiology . 24 . 4 . 312–24 . 2015 . 26713079 . 4688331 . 10.5607/en.2015.24.4.312 .
  32. Weisman O, Zagoory-Sharon O, Feldman R . Intranasal oxytocin administration is reflected in human saliva . Psychoneuroendocrinology . 37 . 9 . 1582–86 . September 2012 . 22436536 . 10.1016/j.psyneuen.2012.02.014 . 25253083 .
  33. Huffmeijer R, Alink LR, Tops M, Grewen KM, Light KC, Bakermans-Kranenburg MJ, Ijzendoorn MH . Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration . Neuro Endocrinology Letters . 33 . 1 . 21–25 . 2012 . 22467107 .
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  43. Torloni MR, Gomes Freitas C, Kartoglu UH, Metin Gülmezoglu A, Widmer M . Quality of oxytocin available in low- and middle-income countries: a systematic review of the literature . BJOG: An International Journal of Obstetrics and Gynaecology . 123 . 13 . 2076–86 . December 2016 . 27006180 . 10.1111/1471-0528.13998 . free .
  44. Stanton C, Koski A, Cofie P, Mirzabagi E, Grady BL, Brooke S . Uterotonic drug quality: an assessment of the potency of injectable uterotonic drugs purchased by simulated clients in three districts in Ghana . BMJ Open . 2 . 3 . e000431 . 2012 . 22556159 . 3346944 . 10.1136/bmjopen-2011-000431 .
  45. Hurlemann R, Patin A, Onur OA, Cohen MX, Baumgartner T, Metzler S, Dziobek I, Gallinat J, Wagner M, Maier W, Kendrick KM . Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans . The Journal of Neuroscience . 30 . 14 . 4999–5007 . April 2010 . 20371820 . 6632777 . 10.1523/JNEUROSCI.5538-09.2010 .
  46. Cochran DM, Fallon D, Hill M, Frazier JA . The role of oxytocin in psychiatric disorders: a review of biological and therapeutic research findings . Harvard Review of Psychiatry . 21 . 5 . 219–47 . 2013 . 24651556 . 4120070 . 10.1097/HRP.0b013e3182a75b7d .
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  48. Bakermans-Kranenburg MJ, ((van I Jzendoorn MH)) . Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy . Translational Psychiatry . 3 . 5. e258 . 2013 . 23695233 . 3669921 . 10.1038/tp.2013.34 .
  49. Unkelbach C, Guastella AJ, Forgas JP . Oxytocin selectively facilitates recognition of positive sex and relationship words . Psychological Science . 19 . 11 . 1092–94 . November 2008 . 19076479 . 10.1111/j.1467-9280.2008.02206.x . 19670817 .
  50. Marsh AA, Yu HH, Pine DS, Blair RJ . Oxytocin improves specific recognition of positive facial expressions . Psychopharmacology . 209 . 3 . 225–32 . April 2010 . 20186397 . 10.1007/s00213-010-1780-4 . 4820244 .
  51. Fischer-Shofty M, Shamay-Tsoory SG, Harari H, Levkovitz Y . The effect of intranasal administration of oxytocin on fear recognition . Neuropsychologia . 48 . 1 . 179–84 . 2010 . 19747930 . 10.1016/j.neuropsychologia.2009.09.003 . 34778485 .
  52. Book: Bartz JA, Hollander E . Advances in Vasopressin and Oxytocin – from Genes to Behaviour to Disease . Oxytocin and experimental therapeutics in autism spectrum disorders . 170 . 451–62 . 2008 . 18655901 . 10.1016/S0079-6123(08)00435-4 . 978-0-444-53201-5 . Progress in Brain Research .
  53. Wudarczyk OA, Earp BD, Guastella A, Savulescu J . Could intranasal oxytocin be used to enhance relationships? Research imperatives, clinical policy, and ethical considerations . Current Opinion in Psychiatry . 26 . 5 . 474–84 . 2013 . 23880593 . 3935449 . 10.1097/YCO.0b013e3283642e10 .

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