Oxytocin (medication)

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Oxytocin (medication)
Oxytocin with labels.png
OxitocinaCPK3D.png
Clinical data
Pronunciation /ˌɒksɪˈtoʊsɪn/
Trade names Pitocin, Syntocinon, Viatocinon, others
AHFS/Drugs.com Monograph
MedlinePlus a682685
License data
Pregnancy
category
  • AU:A
Routes of
administration 		Intranasal, intravenous, intramuscular
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Liver and elsewhere (via oxytocinases)
Elimination half-life 1–6 min (IV)
~2 h (intranasal) [4] [5]
Excretion Bile duct and kidney
Identifiers
  • 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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
Formula C43H66N12O12S2
Molar mass 1007.19 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 Yes check.svgY
  • Key:XNOPRXBHLZRZKH-DSZYJQQASA-N Yes check.svgY
   (verify)

Synthetic oxytocin, sold under the brand name Pitocin among others, is a medication made from the peptide oxytocin . [6] [7] 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. [6] For this purpose, it is given by injection either into a muscle or into a vein. [6]

Contents

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 nerve impulse quickly.

The natural occurrence of oxytocin was discovered in 1906. [8] [9] It is on the World Health Organization's List of Essential Medicines. [10]

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). [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]

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, 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]

Use is linked to an increased risk of postpartum depression in the mother. [23]

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]

Pharmacodynamics

In addition to its oxytocin receptor agonism, oxytocin has been found to act as a positive allosteric modulator (PAM) of the μ- and κ-opioid receptors and this may be involved in its analgesic effects. [28] [29] [30] [31] [32] [33]

Pharmacokinetics

Routes of administration

A bag of oxytocin for intravenous infusion Oxytocin intravenous bag.jpg
A bag of oxytocin for intravenous infusion

One IU of oxytocin is the equivalent of about 1.68  μg or mcg of pure peptide. [34]

Chemistry

Peptide analogues of oxytocin with similar actions, for example carbetocin (Duratocin) and demoxytocin (Sandopart), have been developed and marketed for medical use. [43] In addition, small-molecule oxytocin receptor agonists, like TC OT 39, WAY-267464, and LIT-001 have been developed and studied. [43] However, lack of selectivity over vasopressin receptors has so far limited the potential usefulness of small-molecule oxytocin receptor agonists. [43]

History

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 [44] and by Schafer and Mackenzie in 1911. [45]

Oxytocin was the first polypeptide hormone to be sequenced [46] or synthesized. [47] [48] Du Vigneaud was awarded the Nobel Prize in 1955 for his work. [49]

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 and Asian countries, some oxytocin products were found to be counterfeit medications. [50] [51]

Other uses

The trust-inducing property of oxytocin might help those with social anxiety and depression, [52] 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. [53] [54] However, a 2013 meta-analysis only autism spectrum disorder showed a significant combined effect size. [55] A 2022 study found an indication of an effect among autistic children aged 3-5, but not among autistic children aged 5-12. [56]

People using oxytocin show improved recognition for positive social cues over threatening social cues [57] [58] and improved recognition of fear. [59]

See also

Related Research Articles

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References

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  5. 1 2 Huffmeijer 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. PMID   22467107.
  6. 1 2 3 4 5 "Oxytocin". The American Society of Health-System Pharmacists. Archived from the original on 20 May 2015. Retrieved 1 June 2015.
  7. ↑ The Oxford Handbook of Prosocial Behavior. Oxford University Press. 2015. p. 354. ISBN   978-0-19-539981-3. Archived from the original on 1 August 2017.
  8. ↑ Hurlemann R, Grinevich V (2018). Behavioral Pharmacology of Neuropeptides: Oxytocin. Springer. p. 37. ISBN   978-3-319-63739-6.
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  35. ↑ 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.
  36. ↑ 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.
  37. ↑ Mehta AC (1986). "Buccal and oral drugs: induction of labour". Acta Chirurgica Hungarica. 27 (3): 157–63. PMID   3469841.
  38. ↑ De Groot AN, Vree TB, Hekster YA, Pesman GJ, Sweep FC, Van Dongen PJ, et al. (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. S2CID   8615529.
  39. ↑ 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. ISBN   978-0-07-148127-4. 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.
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