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 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, in one meta-analysis only autism spectrum disorder showed a significant combined effect size. [55]

People using oxytocin show improved recognition for positive social cues over threatening social cues [56] [57] and improved recognition of fear. [58]

See also

Related Research Articles

<span class="mw-page-title-main">Vasopressin</span> Mammalian hormone released from the pituitary gland

Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon terminating in the posterior pituitary, and is released from vesicles into the circulation in response to extracellular fluid hypertonicity (hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the circulation from the filtrate in the kidney tubules of the nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure.

<span class="mw-page-title-main">Oxytocin</span> Peptide hormone and neuropeptide

Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include social bonding, love, reproduction, childbirth, and the period after childbirth. Oxytocin is released into the bloodstream as a hormone in response to sexual activity and during childbirth. It is also available in pharmaceutical form. In either form, oxytocin stimulates uterine contractions to speed up the process of childbirth. In its natural form, it also plays a role in maternal bonding and milk production. Production and secretion of oxytocin is controlled by a positive feedback mechanism, where its initial release stimulates production and release of further oxytocin. For example, when oxytocin is released during a contraction of the uterus at the start of childbirth, this stimulates production and release of more oxytocin and an increase in the intensity and frequency of contractions. This process compounds in intensity and frequency and continues until the triggering activity ceases. A similar process takes place during lactation and during sexual activity.

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<span class="mw-page-title-main">Misoprostol</span> Medication to induce abortion and treat ulcers

Misoprostol is a synthetic prostaglandin medication used to prevent and treat stomach and duodenal ulcers, induce labor, cause an abortion, and treat postpartum bleeding due to poor contraction of the uterus. It is taken by mouth when used to prevent gastric ulcers in people taking nonsteroidal anti-inflammatory drugs (NSAID). For abortions it is used by itself or in conjunction with mifepristone or methotrexate. By itself, effectiveness for abortion is between 66% and 90%. For labor induction or abortion, it is taken by mouth, dissolved in the mouth, or placed in the vagina. For postpartum bleeding it may also be used rectally.

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Intranasal drug delivery occurs when particles are inhaled into the nasal cavity and transported directly into the nervous system. Though pharmaceuticals can be injected into the nose, some concerns include injuries, infection, and safe disposal. Studies demonstrate improved patient compliance with inhalation. Treating brain diseases has been a challenge due to the blood brain barrier. Previous studies evaluated the efficacy of delivery therapeutics through intranasal route for brain diseases and mental health conditions. Intranasal administration is a potential route associated with high drug transfer from nose to brain and drug bioavailability.

References

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