Oxytocin

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Oxytocin
Oxytocin with labels.png
OxitocinaCPK3D.png
Names
Pronunciation/ˌɒksɪˈtsɪn/
Trade namesPitocin, Syntocinon, others
  • 1-({(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-16-(4-hydroxybenzyl)-13-[(1S)-1-methylpropyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-4-yl}carbonyl)-L-prolyl-L-leucylglycinamide
Clinical data
Main usesPost partum bleeding, starting labor[1]
Side effectsExcessive contraction of the uterus, nausea, slow heart rate[2]
Pregnancy
category
  • AU: A
Routes of
use
Intranasal, IV, IM
Defined daily dose15 U (by injection, in the nose)[3]
200 U (by mouth)[3]
External links
AHFS/Drugs.comMonograph
Legal
Legal status
Pharmacokinetics
Protein binding30%
MetabolismLiver and elsewhere (via oxytocinases)
Elimination half-life1–6 min (IV)
~2 h (intranasal)[4][5]
ExcretionBiliary and kidney
Chemical and physical data
FormulaC43H66N12O12S2
Molar mass1007.19 g·mol−1
3D model (JSmol)
  • 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
  • InChI=1S/C43H66N12O12S2/c1-5-22(4)35-42(66)49-26(12-13-32(45)57)38(62)51-29(17-33(46)58)39(63)53-30(20-69-68-19-25(44)36(60)50-28(40(64)54-35)16-23-8-10-24(56)11-9-23)43(67)55-14-6-7-31(55)41(65)52-27(15-21(2)3)37(61)48-18-34(47)59/h8-11,21-22,25-31,35,56H,5-7,12-20,44H2,1-4H3,(H2,45,57)(H2,46,58)(H2,47,59)(H,48,61)(H,49,66)(H,50,60)(H,51,62)(H,52,65)(H,53,63)(H,54,64)/t22-,25-,26-,27-,28-,29-,30-,31-,35-/m0/s1 checkY
  • Key:XNOPRXBHLZRZKH-DSZYJQQASA-N checkY

Synthetic oxytocin, sold under the brand name Pitocin among others, is a medication made from the peptide oxytocin.[2][6] It is used to cause contraction of the uterus to start labor, increase the speed of labor, and to stop bleeding following delivery.[2] For this purpose, it is given by injection either into a muscle or into a vein.[2]

The use of synthetic oxytocin can result in excessive contraction of the uterus that can risk the health of the baby.[2] Common side effects in the mother include nausea and a slow heart rate.[2] Serious side effects include rupture of the uterus and with excessive dose, water intoxication.[2] Allergic reactions including anaphylaxis may also occur.[2]

The natural occurrence of oxytocin was discovered in 1906.[7][8] It is on the World Health Organization's List of Essential Medicines.[9] As of 2014, the wholesale cost in the developing world is US$0.10 to 0.56 per dose.[10]

Medical uses

Labor induction: 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; this drug is registered in many countries to suppress premature labor between 24 and 33 weeks of gestation. It has fewer side effects than drugs previously used for this purpose (ritodrine, salbutamol, and terbutaline).[11]

Oxytocin has not been found to be useful for improving breastfeeding success.[12]

Dosage

The defined daily dose is 15 units by injection or in the nose and 200 units by mouth.[3] For prevention of bleeding after vaginal delivery 5 to 10 units may be given by injection into a vein or muscle.[1] For prevention of bleeding after C section 10 units may be given by injection into a vein and followed by 20 further units over 2 hours.[1] For the treatment of post partum bleeding 5 to 10 units may be given followed by 20 units over two hours.[1] Further doses may be given to a maximum of 60 units may be given.[1] It may also be used to start or increase labor at smaller doses.[1]

Contraindications

Oxytocin injection (synthetic) is contraindicated in any of these conditions:[13]

Side effects

Oxytocin is relatively safe when used at recommended doses, and side effects are uncommon.[14] These maternal events have been reported:[14]

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, and water intoxication, sometimes fatal.

Oxytocin was added to the Institute for Safe Medication Practices's list of High Alert Medications in Acute Care Settings in 2012.[15] The list includes medications that have a high risk for harm if administered incorrectly.[15]

During pregnancy, increased uterine motility has led to decreased heart rate, cardiac arrhythmia, seizures, brain damage, and death in the fetus or neonate.[14]

Use is linked to an increased risk of postpartum depression in the mother.[16]

Certain learning and memory functions are impaired by centrally administered oxytocin.[17] Also, systemic oxytocin administration can impair memory retrieval in certain aversive memory tasks.[18] 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.[19][20]

Pharmacokinetics

Routes of administration

A bag of oxytocin for intravenous infusion

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

History

Its uterine-contracting properties were discovered by British pharmacologist Sir Henry Hallett Dale in 1906.[8] Oxytocin's milk ejection property was described by Ott and Scott in 1910[28] and by Schafer and Mackenzie in 1911.[29]

Oxytocin became the first polypeptide hormone to be sequenced[30] or synthesized.[31][32] Du Vigneaud was awarded the Nobel Prize in 1955 for his work.[33]

Etymology

The word "oxytocin" was coined from the term oxytocic. Greek ὀξύς, oxys, and τόκος, tokos, meaning "quick birth").

Society and culture

Counterfeits

Oxytocin is marketed as a pheromone. Oxytocin in spray form is sold under the brands Attrakt and Connekt. It is not absorbed into the skin when used topically,[citation needed] but it may be inhaled in a manner similar to perfume applied to skin. Oxytocin sprays for insufflation are also sold, but often with little or no oxytocin at all.[citation needed]

In African countries, some oxytocin products were found to be counterfeit medications.[34][35]

Research

The trust-inducing property of oxytocin might help those with social anxiety and depression,[36] 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.[37][38] However, in one meta-analysis only autism spectrum disorder showed a significant combined effect size.[39]

People using oxytocin show improved recognition for positive social cues over threatening social cues [40][41] and improved recognition of fear.[42]

See also

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 "OXYTOCIN injectable - Essential drugs". medicalguidelines.msf.org. Archived from the original on 28 August 2021. Retrieved 4 September 2020.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 "Oxytocin". The American Society of Health-System Pharmacists. Archived from the original on 20 May 2015. Retrieved 1 June 2015.
  3. 3.0 3.1 3.2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 18 August 2020. Retrieved 4 September 2020.
  4. 4.0 4.1 Weisman O, Zagoory-Sharon O, Feldman R (September 2012). "Intranasal oxytocin administration is reflected in human saliva". Psychoneuroendocrinology. 37 (9): 1582–86. doi:10.1016/j.psyneuen.2012.02.014. PMID 22436536.
  5. 5.0 5.1 Huffmeijer R, Alink LR, Tops M, Grewen KM, Light KC, Bakermans-Kranenburg MJ, Ijzendoorn MH (2012). "Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration". Neuro Endocrinology Letters. 33 (1): 21–25. PMID 22467107.
  6. The Oxford Handbook of Prosocial Behavior. Oxford University Press. 2015. p. 354. ISBN 978-0-19-539981-3. Archived from the original on 2017-08-01.
  7. Hurlemann, Rene; Grinevich, Valery (2018). Behavioral Pharmacology of Neuropeptides: Oxytocin. Springer. p. 37. ISBN 978-3319637396. Archived from the original on 2021-08-28. Retrieved 2020-05-25.
  8. 8.0 8.1 Dale HH (May 1906). "On some physiological actions of ergot". The Journal of Physiology. 34 (3): 163–206. doi:10.1113/jphysiol.1906.sp001148. PMC 1465771. PMID 16992821.
  9. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. "Oxytocin". International Drug Price Indicator Guide. Archived from the original on 26 September 2020. Retrieved 20 December 2015.
  11. Budden A, Chen LJ, Henry A (Oct 9, 2014). "High-dose versus low-dose oxytocin infusion regimens for induction of labour at term". The Cochrane Database of Systematic Reviews. 10 (10): CD009701. doi:10.1002/14651858.CD009701.pub2. PMID 25300173.
  12. "Oxytocin use while Breastfeeding". Drugs.com. Archived from the original on 2016-12-15.
  13. "Archived copy". Archived from the original on 2016-12-21. Retrieved 2016-12-16.{{cite web}}: CS1 maint: archived copy as title (link)
  14. 14.0 14.1 14.2 "Pitocin (drug label for professionals)". Rx List. WebMD. Archived from the original on 2011-04-15. Retrieved 2010-09-09.
  15. 15.0 15.1 "High-Alert Medications in Acute Care Settings". Institute For Safe Medication Practices. Archived from the original on 2019-05-06. Retrieved 2019-05-06.
  16. Kroll-Desrosiers, AR; Nephew, BC; Babb, JA; Guilarte-Walker, Y; Moore Simas, TA; Deligiannidis, KM (February 2017). "Association of peripartum synthetic oxytocin administration and depressive and anxiety disorders within the first postpartum year". Depression and Anxiety. 34 (2): 137–46. doi:10.1002/da.22599. PMC 5310833. PMID 28133901.
  17. Gimpl G, Fahrenholz F (April 2001). "The oxytocin receptor system: structure, function, and regulation". Physiological Reviews. 81 (2): 629–83. doi:10.1152/physrev.2001.81.2.629. PMID 11274341. Archived from the original on 2021-08-28. Retrieved 2019-12-11.
  18. de Oliveira LF, Camboim C, Diehl F, Consiglio AR, Quillfeldt JA (January 2007). "Glucocorticoid-mediated effects of systemic oxytocin upon memory retrieval". Neurobiology of Learning and Memory. 87 (1): 67–71. doi:10.1016/j.nlm.2006.05.006. PMID 16997585.
  19. Guastella AJ, Mitchell PB, Mathews F (August 2008). "Oxytocin enhances the encoding of positive social memories in humans". Biological Psychiatry. 64 (3): 256–58. doi:10.1016/j.biopsych.2008.02.008. PMID 18343353.
  20. Rimmele U, Hediger K, Heinrichs M, Klaver P (January 2009). "Oxytocin makes a face in memory familiar". The Journal of Neuroscience. 29 (1): 38–42. doi:10.1523/JNEUROSCI.4260-08.2009. PMC 6664913. PMID 19129382.
  21. Baribeau DA, Anagnostou E (2015). "Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits". Frontiers in Neuroscience. 9: 335. doi:10.3389/fnins.2015.00335. PMC 4585313. PMID 26441508.
  22. 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. PMID 7148921.
  23. Mehta AC (1986). "Buccal and oral drugs: induction of labour". Acta Chirurgica Hungarica. 27 (3): 157–63. PMID 3469841.
  24. De Groot AN, Vree TB, Hekster YA, Pesman GJ, Sweep FC, Van Dongen PJ, Van Roosmalen J (1995). "Bioavailability and pharmacokinetics of sublingual oxytocin in male volunteers" (PDF). The Journal of Pharmacy and Pharmacology. 47 (7): 571–75. doi:10.1111/j.2042-7158.1995.tb06716.x. hdl:2066/21581. PMID 8568623. Archived from the original on 2021-08-28. Retrieved 2019-09-30.
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  39. Bakermans-Kranenburg MJ, van I Jzendoorn MH (2013). "Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy". Translational Psychiatry. 3 (5): e258. doi:10.1038/tp.2013.34. PMC 3669921. PMID 23695233.
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  42. Fischer-Shofty M, Shamay-Tsoory SG, Harari H, Levkovitz Y (2010). "The effect of intranasal administration of oxytocin on fear recognition". Neuropsychologia. 48 (1): 179–84. doi:10.1016/j.neuropsychologia.2009.09.003. PMID 19747930.
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