Oxytocin: Difference between revisions

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{{Distinguish2|OxyContin, a brand of [[oxycodone]]}}
{{DrugProjectFormSinglePage
{{drugbox
|authorTag={{DB}}
| IUPAC_name = 1-({(4''R'',7''S'',10''S'',13''S'',16''S'',19''R'')-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-16-(4-hydroxybenzyl)-13-[(1''S'')-1-methylpropyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-4-yl}carbonyl)-<small>L</small>-prolyl-<small>L</small>-leucylglycinamide
|genericName=Oxytocin
| image = Oxytocin with labels.png
|aOrAn=a
| width = 300px
|drugClass=reproductive control agent
| image2 = Oxytocin3d.png
|indicationType=treatment
| InChI1 = 1/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
|indication=incomplete or [[inevitable abortion]], control of [[postpartum uterine bleeding]], induction or [[stimulation of labor]]
| InChIKey1 = XNOPRXBHLZRZKH-DSZYJQQABJ
|adverseReactions=[[nausea]] and [[vomiting]]
| smiles = O=C(N)CNC(=O)[C@@H](NC(=O)[C@H]3N(C(=O)[C@H]1NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CSSC1)Cc2ccc(O)cc2)[C@@H](C)CC)CCC(=O)N)CC(=O)N)CCC3)CC(C)C
|blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
| CAS_number = 50-56-6
|blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
| ChemSpiderID = 388434
 
| ATC_prefix = H01
* Content
| ATC_suffix = BB02
 
| PubChem = 439302
<!--Adult Indications and Dosage-->
| DrugBank = DB00107
 
| C = 43 | H = 66 | N = 12 | O = 12 | S = 2
<!--FDA-Labeled Indications and Dosage (Adult)-->
| molecular_weight = 1007.19 g/mol
|fdaLIADAdult=[[File:Oxytocin indications.png|600px|thumbnail|left]]
| bioavailability = nil
{{clear}}
| protein_bound = 30%
 
| metabolism = hepatic oxytocinases
=====Induction of labor, Medically indicated=====
| elimination_half-life = 1–6 min
 
| excretion = Biliary and [[Kidney|renal]]
* Oxytocin injection (synthetic) is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable, in order to achieve early vaginal delivery for fetal or maternal reasons.  It is indicated for (1) induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal [[diabetes]], [[pre-eclampsia]] at or near term, when delivery is in the best interest of mother and fetus or when membranes are prematurely ruptured and delivery is indicated; (2) stimulation or reinforcement of labor, as in selected cases of [[uterine inertia]];
| pregnancy_AU = A
 
| legal_UK = POM
* Dosing Information
| legal_US = Rx-only
 
| routes_of_administration = [[Nasal spray|Intranasal]], [[Intravenous therapy|IV]], [[Intramuscular injection|IM]]
:*Dosage of oxytocin is determined by uterine response.  The following dosage information is based upon the various regimens and indications in general use.
}}
 
{{SI}}
:*Intravenous infusion (drip method) is the only acceptable method of administration for the induction or stimulation of labor.
{{CMG}}
 
:*Accurate control of the rate of infusion flow is essential.  An infusion pump or other such device and frequent monitoring of strength of contractions and fetal heart rate are necessary for the safe administration of oxytocin for the induction or stimulation of labor.  If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane.
 
:*An intravenous infusion of a non-oxytocin containing solution should be started.  Physiologic electrolyte solutions should be used except under unusual circumstances.
 
:*To prepare the usual solution for intravenous infusion–one mL (10 units) is combined aseptically with 1,000 mL of a non-hydrating diluent.
 
:*The combined solution, rotated in the infusion bottle to insure thorough mixing, contains 10 mU/mL.  Add the container with dilute oxytocic solution to the system through the use of a constant infusion pump or other such device to control accurately the rate of infusion.
 
:*The initial dose should be no more than 1 to 2 mU/min.  The dose may be gradually increased in increments of no more than 1 to 2 mU/min., until a contraction pattern has been established which is similar to normal labor.
 
:*The fetal heart rate, resting uterine tone, and the frequency, duration, and force of contractions should be monitored.
 
:*The oxytocin infusion should be discontinued immediately in the event of uterine hyperactivity or fetal distress.  Oxygen should be administered to the mother.  The mother and fetus must be evaluated by the responsible physician.
 
=====Control of Postpartum Uterine Bleeding=====
 
*Oxytocin injection (synthetic) is indicated to produce uterine contractions during the third stage of labor and to control [[postpartum bleeding]] or [[hemorrhage]].
 
* Dosing Information
 
:*Intravenous Infusion (Drip Method)—To control postpartum bleeding, 10 to 40 units of oxytocin may be added to 1,000 mL of a nonhydrating diluent and run at a rate necessary to control uterine atony.
 
:*Intramuscular Administration—1 mL (10 units) of oxytocin can be given after delivery of the placenta.
 
====Treatment of Incomplete or Inevitable Abortion====
 
*It is indicated for adjunctive therapy in the management of incomplete or [[inevitable abortion]].  In the first trimester, curettage is generally considered primary therapy.  In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus.  Other means of therapy, however, may be required in such cases.
 
* Dosing Information
 
:*Intravenous infusion with physiologic saline solution, 500 mL, or 5% dextrose in physiologic saline solution to which 10 units of oxytocin have been added should be infused at a rate of 20 to 40 drops/minute.
 
:*Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
 
<!--Off-Label Use and Dosage (Adult)-->
 
<!--Guideline-Supported Use (Adult)-->
|offLabelAdultGuideSupport=* There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport=* There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Pediatric Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=* There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Off-Label Use and Dosage (Pediatric)-->
 
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport=* There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=* There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Contraindications-->
|contraindications=Oxytocin injection (synthetic) is contraindicated in any of the following conditions:


==Overview==
*Significant [[cephalopelvic disproportion]];
'''Oxytocin''' ({{pron-en|ˌɒksɨˈtoʊsɪn}}) is a [[mammal]]ian [[hormone]] that acts primarily as a [[neurotransmitter]] in the [[brain]]. Also known as alpha-hypophamine (α–hypophamine), oxytocin has the distinction of being the very first polypeptide hormone to be sequenced and synthesized biochemically by [[Vincent du Vigneaud]] et al. in 1953.<ref>{{Cite journal| author = du Vigneaud V, Ressler C, Swan JM, Roberts CW, Katsoyannis PG, Gordon S  | title = The synthesis of an octapeptide amide with the hormonal activity of oxytocin | journal = J. Am. Chem. Soc. | volume = 75 | issue = 19 | pages = 4879–80 | year = 1953 | pmid =  | doi = 10.1021/ja01115a553 | url = http://pubs.acs.org/doi/abs/10.1021/ja01115a553 | issn = }}</ref>
*Unfavorable fetal positions or presentations which are undeliverable without conversion prior to delivery, i.e., [[transverse lies]];
*In obstetrical emergencies where the benefit-to-risk ratio for either the fetus or the mother favors surgical intervention;
*In cases of [[fetal distress]] where delivery is not imminent;
*Prolonged use in [[uterine inertia]] or severe toxemia;
*Hypertonic uterine patterns;
*Patients with hypersensitivity to the drug;
*Induction or augmentation of labor in those cases where vaginal delivery is contraindicated, such as cord presentation or [[prolapse]], total [[placenta previa]], and [[vasa previa]].
|warnings=*Oxytocin injection (synthetic) when given for induction or stimulation of labor, must be administered only by the intravenous route and with adequate medical supervision in a hospital.


Oxytocin is best known for its roles in female reproduction: 1) it is released in large amounts after distension of the [[cervix]] and [[uterus]] during labor, and 2) after stimulation of the [[nipple]]s, facilitating [[childbirth|birth]] and [[breastfeeding]]. Recent studies have begun to investigate oxytocin's role in various behaviors, including [[orgasm]], social recognition, [[pair bond]]ing, [[anxiety]], and maternal behaviors.<ref name="pmid19482229">{{Cite journal|author=Lee HJ, Macbeth AH, Pagani JH, Young WS |title=Oxytocin: the great facilitator of life |journal=Progress in Neurobiology |volume=88 |issue=2 |pages=127–51 |year=2009 |month=June |pmid=19482229 |doi=10.1016/j.pneurobio.2009.04.001 |pmc=2689929}}</ref> For this reason, it is sometimes referred to as the "love hormone." <ref>{{Cite web|url=http://www.time.com/time/magazine/article/0,9171,1992405,00.html |title=Thanks, Mom! |author=O'Callaghan, Tiffany |date=7, June 2010 |work=Time Magazine |publisher=Time, Inc. |accessdate=2010-06-08}}</ref>
'''PRECAUTIONS'''


==Actions==
'''General'''
Oxytocin has peripheral (hormonal) actions, and also has actions in the brain. The actions of oxytocin are mediated by specific, high affinity [[oxytocin receptor]]s. The oxytocin receptor is a [[G-protein-coupled receptor]] which requires [[magnesium|Mg]]<sup>2+</sup> and [[cholesterol]]. It belongs to the [[rhodopsin]]-type (class I) group of G-protein-coupled receptors.


===Peripheral (hormonal) actions===
* All patients receiving intravenous oxytocin must be under continuous observation by trained personnel with a thorough knowledge of the drug and qualified to identify complications. A physician qualified to manage any complications should be immediately available.
The peripheral actions of oxytocin mainly reflect secretion from the pituitary gland. (See [[oxytocin receptor]] for more detail on its action.)


* [[Letdown reflex]] &ndash; in [[lactation|lactating]] ([[breastfeeding]]) mothers, oxytocin acts at the [[mammary gland]]s, causing milk to be 'let down' into [[areola|subareolar]] [[sinuses]], from where it can be excreted via the [[nipple]].<ref>http://emedicine.medscape.com/article/976504-overview</ref> Sucking by the [[infant]] at the nipple is relayed by spinal nerves to the [[hypothalamus]]. The stimulation causes neurons that make oxytocin to fire action potentials in intermittent bursts; these bursts result in the secretion of pulses of oxytocin from the neurosecretory nerve terminals of the pituitary gland.
* When properly administered, oxytocin should stimulate uterine contractions similar to those seen in normal labor. Overstimulation of the uterus by improper administration can be hazardous to both mother and fetus. Even with proper administration and adequate supervision, hypertonic contractions can occur in patients whose uteri are hypersensitive to oxytocin.
*[[Uterine contraction]] &ndash; important for [[cervical dilation]] before birth and causes contractions during the second and third stages of [[labor (childbirth)|labor]]. Oxytocin release during breastfeeding causes mild but often painful contractions during the first few weeks of lactation. This also serves to assist the uterus in clotting the placental attachment point postpartum. However, in [[knockout mouse|knockout mice]] lacking the oxytocin receptor, reproductive behavior and [[parturition]] is normal.<ref name="Takayanagi">{{Cite journal|author=Takayanagi Y, Yoshida M, Bielsky IF, ''et al.'' |title=Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=102 |issue=44 |pages=16096–101 |year=2005 |month=November |pmid=16249339 |pmc=1276060 |doi=10.1073/pnas.0505312102}}</ref>


* The relationship between oxytocin and human sexual response is unclear. At least two non-controlled studies have found increases in [[blood plasma|plasma]] oxytocin at orgasm – in both men and women.<ref name="carm1987">{{Cite journal|doi=10.1210/jcem-64-1-27 |author=Carmichael MS, Humbert R, Dixen J, Palmisano G, Greenleaf W, Davidson JM |title=Plasma oxytocin increases in the human sexual response |journal=The Journal of Clinical Endocrinology and Metabolism |volume=64 |issue=1 |pages=27–31 |year=1987 |month=January |pmid=3782434 |url=http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=3782434}}</ref><ref name="pmid8135652">{{Cite journal|doi=10.1007/BF01541618 |author=Carmichael MS, Warburton VL, Dixen J, Davidson JM |title=Relationships among cardiovascular, muscular, and oxytocin responses during human sexual activity |journal=Archives of Sexual Behavior |volume=23 |issue=1 |pages=59–79 |year=1994 |month=February |pmid=8135652}}</ref> Plasma oxytocin levels are notably increased around the time of self stimulated orgasm and are still higher than baseline when measured 5 minutes after self arousal. <ref name="carm1987" /> The authors of one of these studies speculated that oxytocin's effects on muscle contractibility may facilitate sperm and egg transport.<ref name="carm1987" /> In a study that measured oxytocin serum levels in women before and after sexual stimulation the author suggests that oxytocin serves an important role in [[sexual arousal]]. This study found that genital tract stimulation resulted in increased oxytocin immediately after orgasm.<ref name="Blaicher1999">{{Cite journal|author=Blaicher W, Gruber D, Bieglmayer C, Blaicher AM, Knogler W, Huber JC |title=The role of oxytocin in relation to female sexual arousal |journal=Gynecologic and Obstetric Investigation |volume=47 |issue=2 |pages=125–6 |year=1999 |pmid=9949283 |doi=10.1159/000010075}}</ref> Another study that reports increases of oxytocin during sexual arousal states that it could be in response to nipple/areola, genital, and/or genital tract stimulation as confirmed in other mammals.<ref name="Andersonhunt1995">{{Cite journal|doi=10.1159/000292340 |author=Anderson-Hunt M, Dennerstein L |title=Oxytocin and female sexuality |journal=Gynecologic and Obstetric Investigation |volume=40 |issue=4 |pages=217–21 |year=1995 |pmid=8586300}}</ref> Murphy et al. (1987), studying men, found that oxytocin levels were raised throughout sexual arousal and there was no acute increase at orgasm.<ref name="pmid3654918">{{Cite journal|doi=10.1210/jcem-65-4-738 |author=Murphy MR, Seckl JR, Burton S, Checkley SA, Lightman SL |title=Changes in oxytocin and vasopressin secretion during sexual activity in men |journal=The Journal of Clinical Endocrinology and Metabolism |volume=65 |issue=4 |pages=738–41 |year=1987 |month=October |pmid=3654918 |url=http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=3654918}}</ref> A more recent study of men found an increase in plasma oxytocin immediately after orgasm, but only in a portion of their sample that did not reach statistical significance. The authors noted that these changes "may simply reflect contractile properties on reproductive tissue."<ref name="pmid12697037">{{Cite journal|doi=10.1677/joe.0.1770057 |author=Krüger TH, Haake P, Chereath D, ''et al.'' |title=Specificity of the neuroendocrine response to orgasm during sexual arousal in men |journal=The Journal of Endocrinology |volume=177 |issue=1 |pages=57–64 |year=2003 |month=April |pmid=12697037 |url=http://joe.endocrinology-journals.org/cgi/pmidlookup?view=long&pmid=12697037}}</ref>
* Except in unusual circumstances, oxytocin should not be administered in the following conditions: [[prematurity]], borderline cephalopelvic disproportion, previous major surgery on the cervix or uterus including caesarean section, overdistention of the uterus, grand multiparity or invasive cervical carcinoma. Because of the variability of the combinations of factors which may be present in the conditions above, the definition of ‘‘unusual circumstances’’ must be left to the judgement of the physician. The decision can only be made by carefully weighing the potential benefits which oxytocin can provide in a given case against rare but definite potential for the drug to produce hypertonicity or tetanic spasm.
It is also important to note that more studies have been done to examine sexual arousal in women compared to men. Women experience longer [[orgasm]]s compared to men and have a more complex reproductive endocrine system with clearly identified cycles such as, menstruation, lactation, menopause, and pregnancy.<ref name="Bancroft2005">{{Cite journal|author=Bancroft J |title=The endocrinology of sexual arousal |journal=The Journal of Endocrinology |volume=186 |issue=3 |pages=411–27 |year=2005 |month=September |pmid=16135662 |doi=10.1677/joe.1.06233}}</ref> This allows more opportunities to measure and examine the hormones related to sexual arousal.


Oxytocin evokes feelings of contentment, reductions in anxiety, and feelings of calmness and security around the mate.<ref name="Meyer2007">{{Cite journal|first=Dixie |last=Meyer |year=2007 |title=Selective Serotonin Reuptake Inhibitors and Their Effects on Relationship Satisfaction |journal=The Family Journal |volume=15 |issue=4 |pages=392–397 |doi=10.1177/1066480707305470}}</ref> In order to reach full orgasm{{Citation needed|date=January 2010}}, it is necessary that brain regions associated with behavioral control, fear and anxiety are deactivated; which allows individuals to let go of fear and anxiety during sexual arousal. Many studies have already shown a correlation of oxytocin with human bonding, increases in trust, and decreases in fear.  One study confirmed that there was a positive correlation between oxytocin plasma levels and an anxiety scale measuring the adult romantic attachment.<ref name="Marazziti2006">{{Cite journal|author=Marazziti D, Dell'Osso B, Baroni S, ''et al.'' |title=A relationship between oxytocin and anxiety of romantic attachment |journal=Clinical Practice and Epidemiology in Mental Health |volume=2 |issue= |pages=28 |year=2006 |pmid=17034623 |pmc=1621060 |doi=10.1186/1745-0179-2-28}}</ref> This suggests that oxytocin may be important for the inhibition of brain regions that are associated with behavioral control, fear, and anxiety, thus allowing orgasm to occur.
* Maternal deaths due to hypertensive episodes, [[subarachnoid hemorrhage]], rupture of the uterus and fetal deaths due to various causes have been reported associated with the use of parenteral oxytocic drugs for induction of labor and for augmentation in the first and second stages of labor.


* Due to its similarity to [[vasopressin]], it can reduce the excretion of [[urine]] slightly. In several species, oxytocin can stimulate sodium excretion from the kidneys (natriuresis), and in humans, high doses of oxytocin can result in [[hyponatremia]].
* Oxytocin has been shown to have an intrinsic antidiuretic effect, acting to increase water reabsorption from the glomerular filtrate.  Consideration should, therefore, be given to the possibility of water intoxication, particularly when oxytocin is administered continuously by infusion and the patient is receiving fluids by mouth.
|clinicalTrials=* The following adverse reactions have been reported in the mother:


* Oxytocin and oxytocin receptors are also found in the [[heart]] in some rodents, and the hormone may play a role in the embryonal development of the heart by promoting [[cardiomyocyte]] differentiation.<ref name="pmid12093924">{{Cite journal|author=Paquin J, Danalache BA, Jankowski M, McCann SM, Gutkowska J |title=Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=99 |issue=14 |pages=9550–5 |year=2002 |month=July |pmid=12093924 |pmc=123178 |doi=10.1073/pnas.152302499}}</ref><ref name="pmid15316117">{{Cite journal|author=Jankowski M, Danalache B, Wang D, ''et al.'' |title=Oxytocin in cardiac ontogeny |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=101 |issue=35 |pages=13074–9 |year=2004 |month=August |pmid=15316117 |pmc=516519 |doi=10.1073/pnas.0405324101}}</ref> However, the absence of either oxytocin or its receptor in [[knockout mouse|knockout mice]] has not been reported to produce cardiac insufficiencies.<ref name="Takayanagi" />
:*[[Anaphylactic]] reaction
:*[[Postpartum hemorrhage]]
:*[[Cardiac arrhythmia]]
:*Fatal [[afibrinogenemia]]
:*[[Nausea]]
:*[[Vomiting]]
:*[[Premature ventricular contractions]]
:*[[Pelvic hematoma]]
:*Excessive dosage or hypersensitivity to the drug may result in [[uterine hypertonicity]], spasm, tetanic contraction or rupture of the uterus.


* Modulation of [[hypothalamic-pituitary-adrenal axis]] activity. Oxytocin, under certain circumstances, indirectly inhibits release of [[adrenocorticotropic hormone]] and [[cortisol]] and, in those situations, may be considered and antagonist of [[vasopressin]].<ref name="isbn83-200-1415-8">{{Cite book|author=Hartwig, Walenty |title=Endokrynologia praktyczna |publisher=Państwowy Zakład Wydawnictw Lekarskich |location=[[Warsaw]] |year=1989 |pages= |isbn=83-200-1415-8}}{{Page needed|date=September 2010}}</ref>
*The possibility of increased blood loss and [[afibrinogenemia]] should be kept in mind when administering the drug.


* [[Autism]]. Oxytocin may play a role in autism and may be an effective [[Autism therapies#Prescription medication|treatment for autism]]'s repetitive and affiliative behaviors.<ref>{{Cite journal|author=Bartz JA, Hollander E |title=Oxytocin and experimental therapeutics in autism spectrum disorders |journal=Progress in Brain Research |volume=170 |issue= |pages=451–62 |year=2008 |pmid=18655901 |doi=10.1016/S0079-6123(08)00435-4}}</ref> Oxytocin treatments also resulted in an increased retention of affective speech in adults with autism.<ref name="Gregory2009">{{Cite journal|author=Jacob S, Brune CW, Carter CS, Leventhal BL, Lord C, Cook EH |title=Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism |journal=Neuroscience Letters |volume=417 |issue=1 |pages=6–9 |year=2007 |month=April |pmid=17383819 |pmc=2705963 |doi=10.1016/j.neulet.2007.02.001}}</ref> Two related studies in adults, in 2003 and 2007, found that oxytocin decreased repetitive behaviors and improved interpretation of emotions. More recently, intranasal administration of oxytocin was found to increase emotion recognition in children as young as 12 who are diagnosed with autism spectrum disorders <ref name="Guastella2010">{{Cite journal|author=Guastella AJ, Einfeld EL, Gray, K, Rinehart N, Tonge B, Lambert TJ, Hickie IB |title=Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders |journal=Biological Psychiatry |volume=67|issue=7 |pages=692–694 |year=2010 |month=April |pmid=19897177 |doi=10.1016/j.biopsych.2009.09.020}}</ref> Oxytocin has also been implicated in the etiology of autism with one report suggesting that autism is correlated with genomic deletion of the gene containing the oxytocin receptor gene ([[Oxytocin receptor|OXTR]]).  Studies involving Caucasian and Finnish samples and Chinese Han families provide support for the relationship of OXTR with autism.<ref name="Gregory2009"/><ref name="Wermter2009">{{Cite journal|author=Wermter AK, Kamp-Becker I, Hesse P, Schulte-Körne G, Strauch K, Remschmidt H |title=Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level |journal=American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics |volume= 153B|issue= 2|pages= 629–39|year=2009 |month=September |pmid=19777562 |doi=10.1002/ajmg.b.31032}}</ref> Autism may also be associated by an aberrant methylation of OXTR, as reported by Gregory and colleagues.<ref name="Gregory2009"/>  After treatment with inhaled oxytocin, autistic patients exhibit more appropriate social behavior.<ref name="Andaria_2010">{{Cite journal| author = Andaria E, Duhamela J-R, Zallab T, Herbrechtb E, Leboyerb M, Sirigu A | year =2010 | title = Promoting social behavior with oxytocin in high-functioning autism spectrum disorders | journal = Proc. Natl. Acad. Sci. U.S.A. | doi = 10.1073/pnas.0910249107 | url = http://www.pnas.org/content/early/2010/02/05/0910249107.abstract | laysource = Scientific American | laysummary = http://www.scientificamerican.com/podcast/episode.cfm?id=oxytocin-may-alleviate-some-autism-10-02-16 | pmid = 20160081 | volume = 107 | issue = 9 | pages = 4389–94 | pmc = 2840168 }}</ref> While this research suggests some promise, further clinical trials of oxytocin are required to demonstrate potential benefit and side effects in the treatment of autism. As such, researchers do not recommend use of oxytocin as a treatment for autism outside of clinical trials.
*Severe water intoxication with convulsions and coma has occurred, and is associated with a slow oxytocin infusion over a 24-hour periodMaternal death due to oxytocin-induced water intoxication has been reported.


* Increasing [[Trust (sociology)|trust]] and reducing [[fear]]. In a risky investment game, experimental subjects given nasally administered oxytocin displayed "the highest level of trust" twice as often as the control group. Subjects who were told that they were interacting with a computer showed no such reaction, leading to the conclusion that oxytocin was not merely affecting [[risk-aversion]].<ref name="pmid15931222">{{Cite journal|author=Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E |title=Oxytocin increases trust in humans |journal=Nature |volume=435 |issue=7042 |pages=673–6 |year=2005 |month=June |pmid=15931222 |doi=10.1038/nature03701}}</ref> Nasally administered oxytocin has also been reported to reduce fear, possibly by inhibiting the [[amygdala]] (which is thought to be responsible for fear responses).<ref name="pmid16339042">{{Cite journal|author=Kirsch P, Esslinger C, Chen Q, ''et al.'' |title=Oxytocin modulates neural circuitry for social cognition and fear in humans |journal=The Journal of Neuroscience |volume=25 |issue=49 |pages=11489–93 |year=2005 |month=December |pmid=16339042 |doi=10.1523/JNEUROSCI.3984-05.2005}}</ref> Some researchers have argued that oxytocin has a general enhancing effect on all social emotions since intranasal administration of oxytocin also increases [[envy]] and [[schadenfreude]].<ref>{{Cite journal|author=Shamay-Tsoory SG, Fischer M, Dvash J, Harari H, Perach-Bloom N, Levkovitz Y |title=Intranasal administration of oxytocin increases envy and schadenfreude (gloating) |journal=Biological Psychiatry |volume=66 |issue=9 |pages=864–70 |year=2009 |month=November |pmid=19640508 |doi=10.1016/j.biopsych.2009.06.009}}</ref>
*The following adverse reactions have been reported in the fetus or infant:


* Affecting [[generosity]] by increasing empathy during perspective taking.  In a [[neuroeconomics]] experiment, [[intranasal]] oxytocin increased generosity in the [[Ultimatum Game]] by 80% but has no effect in the [[Dictator Game]] that measures altruism.  Perspective-taking is not required in the Dictator Game, but the researchers in this experiment explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants which role they would be in.<ref name="pmid17987115">{{Cite journal|author=Zak PJ, Stanton AA, Ahmadi S |title=Oxytocin increases generosity in humans |journal=PLoS ONE |volume=2 |issue=11 |pages=e1128 |year=2007 |pmid=17987115 |pmc=2040517 |doi=10.1371/journal.pone.0001128}}</ref>
*Due to induced uterine mobility:


* Certain learning and memory functions are impaired by centrally administered oxytocin.<ref name="Gimpl" /> Also, systemic oxytocin administration can impair memory retrieval in certain aversive memory tasks.<ref name="pmid16997585">{{Cite journal|author=de Oliveira LF, Camboim C, Diehl F, Consiglio AR, Quillfeldt JA |title=Glucocorticoid-mediated effects of systemic oxytocin upon memory retrieval |journal=Neurobiology of Learning and Memory |volume=87 |issue=1 |pages=67–71 |year=2007 |month=January |pmid=16997585 |doi=10.1016/j.nlm.2006.05.006}}</ref> Interestingly, oxytocin does seem to facilitate learning and memory specifically for social information. Healthy males administered intranasal oxytocin show improved memory for human faces, particularly happy faces.<ref name="Guastella2008">{{Cite journal|author=Guastella AJ, Mitchell PB, Matthews F|title=Oxytocin enhances the encoding of positive social memories in humans |journal=Biological Psychiatry |volume=64|issue=3 |pages=256–8 |year=2008 |month=August |pmid=18343353 |doi=10.1016/j.biopsych.2008.02.008}}</ref><ref name="Rimelle2009">{{Cite journal|author=Rimmele U, Hediger K, Heinrichs M, Klaver P|title=Oxytocin makes a face in memory familiar |journal=Journal of Neuroscience|volume=29|issue=1 |pages=38–42 |year=2009 |month= |pmid=19129382 |doi=10.1523/JNEUROSCI.4260-08.2009}}</ref> They also show improved recognition for positive social cues over threatening social cues <ref name="Unkelbach2008">{{Cite journal|author=Unkelbach C, Guastella AJ, Forgas JP|title=Oxytocin selectively facilitates recognition of positive sex and relationship words |journal=Pschological Science|volume=19|issue=11 |pages=1092–4 |year=2008 |month=Nov |pmid=19076479 |doi=10.1111/j.1467-9280.2008.02206.x}}</ref><ref name="Marsh2010">{{Cite journal|author=Marsh AA, Yu HH, Pine DS, Blair RJ|title=Oxytocin improves specific recognition of positive facial expressions |journal=Psychopharmacology|volume=209|issue=3 |pages=225–32 |year=2010 |month=April |pmid=20186397 |doi=10.1007/s00213-010-1780-4}}</ref>
:*[[Bradycardia]]
:*[[Premature ventricular contractions]] and other [[arrhythmias]]
:*Permanent CNS or brain damage
:*Fetal death


* Empathy in healthy males has been shown to be increased after intranasal oxytocin<ref name="pmid20371820">{{Cite journal| author = Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC | title = Oxytocin improves "mind-reading" in humans | journal = Biological Psychiatry | volume = 61 | issue = 6 | pages = 731–3 | year = 2010 | month = April | pmid = 20371820 | doi = 10.1523/JNEUROSCI.5538-09.2010 | url = | issn = }}</ref><ref name="pmid20371820">{{Cite journal| author = Hurlemann R, Patin A, Onur OA, Cohen MX, Baumgartner T, Metzler S, Dziobek I, Gallinat J, Wagner M, Maier W, Kendrick KM | title = Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans | journal = J. Neurosci. | volume = 30 | issue = 14 | pages = 4999–5007 | year = 2010 | month = April | pmid = 20371820 | doi = 10.1523/JNEUROSCI.5538-09.2010 | url = | issn = }}</ref> This is most likely due to the effect of oxytocin in enhancing eye gaze.<ref name=" Guastellab2008">{{Cite journal|author=Guastella AJ, Mitchell PB, Dadds MR|title=Oxytocin increases gaze to the eye region of human faces |journal=Biological Psychiatry |volume=63|issue=1 |pages=3–5 |year=2008 |month=Jan |pmid= 17888410|doi=10.1016/j.biopsych.2007.06.026}}</ref> There is some discussion about which aspect of empathy oxytocin might alter, for example cognitive vs emotional empathy.<ref name="pmid19102589">{{Cite journal| author = Singer T, Snozzi R, Bird G, Petrovic P, Silani G, Heinrichs M, Dolan RJ | title = Effects of oxytocin and prosocial behavior on brain responses to direct and vicariously experienced pain | journal = Emotion | volume = 8 | issue = 6 | pages = 781–91 | year = 2008 | month = December | pmid = 19102589 | pmc = 2672051 | doi = 10.1037/a0014195 | url = | issn = }}</ref>


=== Actions within the brain ===<!-- This section is linked from [[Zoophilia]] -->
*Due to use of oxytocin in the mother:
Oxytocin secreted from the [[pituitary gland]] cannot re-enter the brain because of the [[blood-brain barrier]]. Instead, the behavioral effects of oxytocin are thought to reflect release from centrally projecting oxytocin neurons, different from those that project to the pituitary gland, or which are collaterals from them.<ref name="Ross"/> Oxytocin receptors are expressed by neurons in many parts of the brain and spinal cord, including the [[amygdala]], [[ventromedial hypothalamus]], [[septum]], [[nucleus accumbens]] and [[brainstem]].


* Sexual arousal. Oxytocin injected into the [[cerebrospinal fluid]] causes spontaneous [[erection]]s in rats,<ref name="Gimpl">{{Cite journal|author=Gimpl G, Fahrenholz F |title=The oxytocin receptor system: structure, function, and regulation |journal=Physiological Reviews |volume=81 |issue=2 |pages=629–83 |year=2001 |month=April |pmid=11274341 |url=http://physrev.physiology.org/cgi/pmidlookup?view=long&pmid=11274341}}</ref> reflecting actions in the hypothalamus and spinal cord. Centrally administrated oxytocin receptor antagonists can prevent non contact erections, which is a measure of sexual arousal. Studies using oxytocin antagonists in female rats provide data that oxytocin increases [[lordosis]], indicating an increase in sexual receptivity.<ref name="Bancroft2005"/>
:*Neonatal [[retinal hemorrhage]]
:*Low Apgar scores at five minutes
:*[[Neonatal jaundice]]
|postmarketing=*There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
<!--Drug Interactions-->
|drugInteractions=*Severe hypertension has been reported when oxytocin was given three to four hours following prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia.  Cyclopropane anesthesia may modify oxytocin’s cardiovascular effects, so as to produce unexpected results such as [[hypotension]].  Maternal sinus bradycardia with abnormal atrioventricular rhythms has also been noted when oxytocin was used concomitantly with cyclopropane anesthesia.
|FDAPregCat=C
|useInPregnancyFDA='''Pregnancy Category C'''
*There are no known indications for use of oxytocin in the first and second trimester of pregnancy other than in relation to spontaneous or induced abortion. Based on the wide experience with this drug and its chemical structure and pharmacological properties, it would not be expected to present a risk of fetal abnormalities when used as indicated.


* Bonding. In the [[Prairie Vole]], oxytocin released into the brain of the female during sexual activity is important for forming a monogamous pair bond with her sexual partner. [[Vasopressin]] appears to have a similar effect in males.<ref>[http://www.americanscientist.org/template/AssetDetail/assetid/14756 Vacek M,  High on Fidelity. What can voles teach us about monogamy? ]</ref> Oxytocin has a role in social behaviors in many species, and so it seems likely that it also does in humans.
*Nonteratogenic Effects—See ADVERSE REACTIONS in the fetus or infant.
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''


* [[Maternal bond|Maternal behavior]]. Female rats given oxytocin [[Receptor antagonist|antagonists]] after giving birth do not exhibit typical maternal behavior.<ref name="pmid3819639">{{Cite journal|author=van Leengoed E, Kerker E, Swanson HH |title=Inhibition of post-partum maternal behaviour in the rat by injecting an oxytocin antagonist into the cerebral ventricles |journal=The Journal of Endocrinology |volume=112 |issue=2 |pages=275–82 |year=1987 |month=February |pmid=3819639 |doi=10.1677/joe.0.1120275}}</ref> By contrast, virgin female sheep show maternal behavior towards foreign lambs upon [[cerebrospinal fluid]] infusion of oxytocin, which they would not do otherwise.<ref name="urlBritish Society for Neuroendocrinology - 22. The Neurobiology of Social Bonds">{{Cite web| url = http://neuroendo.org.uk/index.php/content/view/34/11/ | title = The Neurobiology of Social Bonds | author = Kendrick KM | authorlink = | coauthors = | date = 2004-01-01 | format = | work = | publisher = British Society for Neuroendocrinology | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2009-04-13}}</ref> Oxytocin is involved in the initiation of maternal behavior not its maintenance, for example, it is higher in mothers after they interact with unfamiliar children rather than their own.<ref>Bick J, Mary Dozier M. (2010). Mothers' concentrations of oxytocin following close, physical interactions with biological and nonbiological children. Developmental Psychobiology, 52: 100 - 107. {{doi|10.1002/dev.20411}}</ref>
*There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery='''Antepartum'''
*Oxytocin injection (synthetic) is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable, in order to achieve early vaginal delivery for fetal or maternal reasons.  It is indicated for (1) induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, [[pre-eclampsia]] at or near term, when delivery is in the best interest of mother and fetus or when membranes are prematurely ruptured and delivery is indicated; (2) stimulation or reinforcement of labor, as in selected cases of uterine inertia; (3) adjunctive therapy in the management of incomplete or inevitable abortion.  In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases.


* According to some studies in animals, oxytocin inhibits the development of tolerance to various addictive drugs ([[opiate]]s, [[cocaine]], [[ethanol|alcohol]]) and reduces [[withdrawal]] symptoms.<ref name="pmid9924746">{{Cite journal|author=Kovács GL, Sarnyai Z, Szabó G |title=Oxytocin and addiction: a review |journal=Psychoneuroendocrinology |volume=23 |issue=8 |pages=945–62 |year=1998 |month=November |pmid=9924746 |doi=10.1016/S0306-4530(98)00064-X}}</ref>
'''Postpartum'''
*Oxytocin injection (synthetic) is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.
|useInNursing=* It is not known whether this drug is excreted in human milk.  Because many drugs are excreted in human milk, caution should be exercised when oxytocin is administered to a nursing woman.
|useInPed=* There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=* There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=* There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=* There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=* There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=* There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=* There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=* There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.


* Preparing fetal neurons for delivery. Crossing the placenta, maternal oxytocin reaches the fetal brain and induces a switch in the action of neurotransmitter [[GABA]] from excitatory to inhibitory on fetal cortical neurons. This silences the fetal brain for the period of delivery and reduces its vulnerability to [[hypoxia (medical)|hypoxic damage]].<ref name="pmid17170309">{{Cite journal|author=Tyzio R, Cossart R, Khalilov I, ''et al.'' |title=Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery |journal=Science |volume=314 |issue=5806 |pages=1788–92 |year=2006 |month=December |pmid=17170309 |doi=10.1126/science.1133212}}</ref>
<!--Administration and Monitoring-->
|administration=* Dosage of oxytocin is determined by uterine response. The following dosage information is based upon the various regimens and indications in general use.


* [[MDMA]] (ecstasy) may increase feelings of love, empathy and connection to others by stimulating oxytocin activity via activation of [[serotonin]] [[5-HT1A receptor]]s, if initial studies in animals apply to humans.<ref name="pmid17383105">{{Cite journal|author=Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS |title=A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy") |journal=Neuroscience |volume=146 |issue=2 |pages=509–14 |year=2007 |month=May |pmid=17383105 |doi=10.1016/j.neuroscience.2007.02.032}}</ref> The [[anxiolytic]] [[Buspar]] (buspirone) also appears to produce some or all of its effect via 5-HT1A receptor-induced oxytocin stimulation.<ref name="pmid9025112">{{Cite journal| author = Uvnäs-Moberg K, Hillegaart V, Alster P, Ahlenius S | title = Effects of 5-HT agonists, selective for different receptor subtypes, on oxytocin, CCK, gastrin and somatostatin plasma levels in the rat | journal = Neuropharmacology | volume = 35 | issue = 11 | pages = 1635–40 | year = 1996 | pmid = 9025112 | doi = 10.1016/S0028-3908(96)00078-0| url = | issn = }}</ref><ref name="pmid8771561">{{Cite journal| author = Chiodera P, Volpi R, Capretti L, Caffarri G, Magotti MG, Coiro V | title = Different effects of the serotonergic agonists buspirone and sumatriptan on the posterior pituitary hormonal responses to hypoglycemia in humans | journal = Neuropeptides | volume = 30 | issue = 2 | pages = 187–92 | year = 1996 | month = April | pmid = 8771561 | doi = 10.1016/S0143-4179(96)90086-4| url = | issn = }}</ref>
'''Induction or Stimulation of Labor'''


==Drug forms==
*Intravenous infusion (drip method) is the only acceptable method of administration for the induction or stimulation of labor.
Synthetic oxytocin is sold as proprietary [[medication]] under the trade names '''Pitocin''' and '''Syntocinon''' and also as [[generic drug|generic]] oxytocin. Oxytocin is destroyed in the [[gastrointestinal tract]], and therefore must be administered by injection or as [[nasal spray]]. Oxytocin has a [[half-life]] of typically about three minutes in the blood. Oxytocin given [[Intravenous therapy|intravenously]] does not enter the brain in significant quantities - it is excluded from the brain by the [[blood-brain barrier]]. There is no evidence for significant central nervous system entry of oxytocin by nasal spray. Oxytocin nasal sprays have been used to stimulate breastfeeding but the efficacy of this approach is doubtful.<ref name="pmid16223754">{{Cite journal|author=Fewtrell MS, Loh KL, Blake A, Ridout DA, Hawdon J |title=Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants |journal=Archives of Disease in Childhood. Fetal and Neonatal Edition |volume=91 |issue=3 |pages=F169–74 |year=2006 |month=May |pmid=16223754 |pmc=2672698 |doi=10.1136/adc.2005.081265}}</ref>


Injected oxytocin analogues are used for [[labor induction]] and to support labor in case of non-progression of parturition. It has largely replaced [[ergometrine]] as the principal agent to increase uterine tone in acute [[postpartum haemorrhage]]. Oxytocin is also used in [[veterinary medicine]] to facilitate birth and to stimulate milk release. The [[tocolytic]] agent [[atosiban]] ('''Tractocile''') acts as an [[receptor antagonist|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]]).
*Accurate control of the rate of infusion flow is essential.  An infusion pump or other such device and frequent monitoring of strength of contractions and fetal heart rate are necessary for the safe administration of oxytocin for the induction or stimulation of labor. If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane.


Some have suggested that the trust-inducing property of oxytocin might help those who suffer from [[Social anxiety|social anxieties]] and [[mood disorders]], while others have noted the potential for abuse with [[confidence trick]]s<ref name="pmid18579733">{{Cite journal|author=Petrovic P, Kalisch R, Singer T, Dolan RJ |title=Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity |journal=The Journal of Neuroscience |volume=28 |issue=26 |pages=6607–15 |year=2008 |month=June |pmid=18579733 |pmc=2647078 |doi=10.1523/JNEUROSCI.4572-07.2008}}</ref><ref name="urlTo sniff at danger - Mind Matters - Health And Fitness - smh.com.au">{{Cite web| url = http://www.smh.com.au/news/mind-matters/to-sniff-at-danger/2006/01/12/1136956247384.html | title = To sniff at danger - Mind Matters  | author = | authorlink = | coauthors = | date = 2006-01-12 | work = Health And Fitness | publisher = Boston Globe | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2009-04-13}}</ref> and military applications.<ref name="pmid19693065">{{Cite journal|author=Dando M |title=Biologists napping while work militarized |journal=Nature |volume=460 |issue=7258 |pages=950–1 |year=2009 |month=August |pmid=19693065 |doi=10.1038/460950a |laysummary=http://www.reuters.com/article/newsOne/idUSTRE57I4VL20090819 |laysource=Reuters}}</ref>
*An intravenous infusion of a non-oxytocin containing solution should be started. Physiologic electrolyte solutions should be used except under unusual circumstances.


===Potential adverse reactions===
*To prepare the usual solution for intravenous infusion–one mL (10 units) is combined aseptically with 1,000 mL of a non-hydrating diluent.
Oxytocin is relatively safe when used at recommended doses, and side effects are uncommon.<ref name="rxlist">{{Cite web|url= http://www.rxlist.com/pitocin-drug.htm |title= Pitocin (drug label for professionals) |publisher= WebMD |work= Rx List |accessdate=2010-09-09}}</ref> The following maternal [[adverse drug reaction|events]] have been reported:<ref name="rxlist"/>


*[[Subarachnoid hemorrhage]]
*The combined solution, rotated in the infusion bottle to insure thorough mixing, contains 10 mU/mL.  Add the container with dilute oxytocic solution to the system through the use of a constant infusion pump or other such device to control accurately the rate of infusion.
*[[Tachycardia|Increased heart rate]]
*[[hypotension|Decreased blood pressure]]
*[[Cardiac arrhythmia]] and [[premature ventricular contraction]]
*Impaired uterine blood flow
*Pelvic [[hematoma]]
*[[Fibrinogen#Fibrinogen_deficiency|Afibrinogenonemia]], which can lead to hemorrhage and death
*[[Anaphylaxis]]
*[[Nausea]] and [[vomiting]]


Excessive dosage or long term administration (over a period of 24 hours or longer) have been known to result in tetanic uterine contractions, [[uterine rupture]], postpartum hemorrhage, and [[water intoxication]], sometimes fatal.
*The initial dose should be no more than 1 to 2 mU/min.  The dose may be gradually increased in increments of no more than 1 to 2 mU/min., until a contraction pattern has been established which is similar to normal labor.


Increased uterine motility has led to the following complications in the fetus/neonate:<ref name="rxlist"/>
*The fetal heart rate, resting uterine tone, and the frequency, duration, and force of contractions should be monitored.


*[[Bradycardia|Decreased heart rate]] or heart rate decelerations
*The oxytocin infusion should be discontinued immediately in the event of uterine hyperactivity or fetal distress.  Oxygen should be administered to the mother.  The mother and fetus must be evaluated by the responsible physician.
*Cardiac arrhythmia
*[[Brain damage]]
*Seizures
*Death


In addition, use of pitocin in the mother has been associated with neonatal [[jaundice]], [[retinal hemorrhage]], and low five-minute [[Apgar score]].
'''Control of Postpartum Uterine Bleeding'''


==Synthesis, storage, and release==
{{protein
| Name = oxytocin, prepro- (neurophysin I)
| caption =
| image =
| width =
| HGNCid = 8528
| Symbol = OXT
| AltSymbols = OT
| EntrezGene = 5020
| OMIM = 167050
| RefSeq = NM_000915
| UniProt = P01178
| PDB =
| ECnumber =
| Chromosome = 20
| Arm = p
| Band = 13
| LocusSupplementaryData =
}}
The oxytocin [[peptide]] is synthesized as an inactive precursor protein from the ''OXT'' [[gene]].<ref name="pmid2991279">{{Cite journal| author = Sausville E, Carney D, Battey J | title = The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line | journal = J. Biol. Chem. | volume = 260 | issue = 18 | pages = 10236–41 | year = 1985 | month = August | pmid = 2991279 | doi = | url = | issn = }}</ref><ref name="pmid1968469">{{Cite journal| author = Repaske DR, Phillips JA, Kirby LT, Tze WJ, D'Ercole AJ, Battey J | title = Molecular analysis of autosomal dominant neurohypophyseal diabetes insipidus | journal = J. Clin. Endocrinol. Metab. | volume = 70 | issue = 3 | pages = 752–7 | year = 1990 | month = March | pmid = 1968469 | doi = 10.1210/jcem-70-3-752| url = | issn = }}</ref><ref name="pmid1978246">{{Cite journal| author = Summar ML, Phillips JA, Battey J, Castiglione CM, Kidd KK, Maness KJ, Weiffenbach B, Gravius TC | title = Linkage relationships of human arginine vasopressin-neurophysin-II and oxytocin-neurophysin-I to prodynorphin and other loci on chromosome 20 | journal = Mol. Endocrinol. | volume = 4 | issue = 6 | pages = 947–50 | year = 1990 | month = June | pmid = 1978246 | doi = 10.1210/mend-4-6-947| url = | issn = }}</ref>  This precursor protein also includes the oxytocin carrier protein [[neurophysin I]].<ref name="pmid6153132">{{Cite journal| author = Brownstein MJ, Russell JT, Gainer H | title = Synthesis, transport, and release of posterior pituitary hormones | journal = Science | volume = 207 | issue = 4429 | pages = 373–8 | year = 1980 | month = January | pmid = 6153132 | doi = 10.1126/science.6153132| url = | issn = }}</ref>  The inactive precursor protein is progressively hydrolyzed into smaller fragments (one of which is neurophysin I) via a series of enzymes. The last hydrolysis which releases the active oxytocin nonapeptide is catalyzed by [[peptidylglycine alpha-amidating monooxygenase]] (PAM).<ref name="pmid2769155">{{Cite journal| author = Sheldrick EL, Flint AP | title = Post-translational processing of oxytocin-neurophysin prohormone in the ovine corpus luteum: activity of peptidyl glycine alpha-amidating mono-oxygenase and concentrations of its cofactor, ascorbic acid | journal = J. Endocrinol. | volume = 122 | issue = 1 | pages = 313–22 | year = 1989 | month = July | pmid = 2769155 | doi = 10.1677/joe.0.1220313| url = | issn = }}</ref>


The activity of the PAM enzyme system is dependent upon [[vitamin C|ascorbate]] which is a necessary vitamin cofactor. By chance, it was discovered that sodium ascorbate by itself stimulated the production of oxytocin from ovarian tissue over a range of concentrations in a dose-dependent manner.<ref name="pmid3668432">{{Cite journal| author = Luck MR, Jungclas B | title = Catecholamines and ascorbic acid as stimulators of bovine ovarian oxytocin secretion | journal = J. Endocrinol. | volume = 114 | issue = 3 | pages = 423–30 | year = 1987 | month = September | pmid = 3668432 | doi = 10.1677/joe.0.1140423 | url = | issn = }}</ref> Many of the same tissues (e.g. ovaries, testes, eyes, adrenals, placenta, thymus, pancreas) where PAM (and oxytocin by default) is found are also known to store higher concentrations of [[vitamin C]].<ref name="pmid1106295">{{Cite journal| author = Hornig D | title = Distribution of ascorbic acid, metabolites and analogues in man and animals | journal = Ann. N. Y. Acad. Sci. | volume = 258 | issue = | pages = 103–18 | year = 1975 | month = September | pmid = 1106295 | doi = 10.1111/j.1749-6632.1975.tb29271.x | url = | issn = }}</ref>
*Intravenous Infusion (Drip Method)—To control postpartum bleeding, 10 to 40 units of oxytocin may be added to 1,000 mL of a nonhydrating diluent and run at a rate necessary to control uterine atony.


===Neural sources===
*Intramuscular Administration—1 mL (10 units) of oxytocin can be given after delivery of the placenta.
In the [[hypothalamus]], oxytocin is made in [[magnocellular neurosecretory cell]]s of the [[supraoptic nucleus|supraoptic]] and [[paraventricular nucleus|paraventricular]] nuclei and is stored in [[Herring bodies]] at the axon terminals in the posterior pituitary. It is then released into the blood from the [[posterior pituitary|posterior lobe]] ([[neurohypophysis]]) of the [[pituitary gland]]. These axons (likely, but dendrites have not been ruled out) have collaterals that innervate oxytocin receptors  in the [[nucleus accumbens]].<ref name="Ross">{{Cite journal|author=Ross HE, Cole CD, Smith Y, ''et al.'' |title=Characterization of the oxytocin system regulating affiliative behavior in female prairie voles |journal=Neuroscience |volume=162 |issue=4 |pages=892–903 |year=2009 |month=September |pmid=19482070 |doi=10.1016/j.neuroscience.2009.05.055 |pmc=2744157}}</ref> The peripheral hormonal and behavioral brain effects of oxytocin it has been suggested are coordinated through its common release through these collaterals.<ref name="Ross"/> Oxytocin is also made by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord.<ref>{{Cite journal|author=Landgraf R, Neumann ID |title=Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication |journal=Frontiers in Neuroendocrinology |volume=25 |issue=3-4 |pages=150–76 |year=2004 |pmid=15589267 |doi=10.1016/j.yfrne.2004.05.001}}</ref> Depending on the species, oxytocin-receptor expressing cells are located in other areas, including the [[amygdala]] and [[bed nucleus]] of the [[stria terminalis]].


In the [[pituitary gland]], oxytocin is packaged in large, dense-core vesicles, where it is bound to [[neurophysin I]] as shown in the inset of the figure; neurophysin is a large [[peptide]] fragment of the larger precursor [[protein]] molecule from which oxytocin is derived by [[enzyme|enzymatic]] cleavage.
'''Treatment of Incomplete or Inevitable Abortion'''


Secretion of oxytocin from the neurosecretory nerve endings is regulated by the electrical activity of the oxytocin cells in the hypothalamus. These cells generate [[action potential]]s that propagate down [[axon]]s to the nerve endings in the pituitary; the endings contain large numbers of oxytocin-containing vesicles, which are released by [[exocytosis]] when the nerve terminals are depolarised.
*Intravenous infusion with physiologic saline solution, 500 mL, or 5% dextrose in physiologic saline solution to which 10 units of oxytocin have been added should be infused at a rate of 20 to 40 drops/minute.


===Non-neural sources===
*Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Outside the brain, oxytocin-containing cells have been identified in several diverse tissues including the [[corpus luteum]],<ref name="pmid7078636">{{Cite journal| author = Wathes DC, Swann RW | title = Is oxytocin an ovarian hormone? | journal = Nature | volume = 297 | issue = 5863 | pages = 225–7 | year = 1982 | month = May | pmid = 7078636 | doi = 10.1038/297225a0 | url = | issn = }}</ref><ref name="pmid6124806">{{Cite journal| author = Wathes DC, Swann RW, Pickering BT, Porter DG, Hull MG, Drife JO | title = Neurohypophysial hormones in the human ovary | journal = Lancet | volume = 2 | issue = 8295 | pages = 410–2 | year = 1982 | month = August | pmid = 6124806 | doi = 10.1016/S0140-6736(82)90441-X | url = | issn = }}</ref> the  [[Leydig cell|interstitial cells of Leydig]],<ref name="pmid3995564">{{Cite journal| author = Guldenaar SE, Pickering BT | title = Immunocytochemical evidence for the presence of oxytocin in rat testis | journal = Cell Tissue Res. | volume = 240 | issue = 2 | pages = 485–7 | year = 1985 | pmid = 3995564 | doi = 10.1007/BF00222364 | url = | issn = }}</ref> the retina,<ref name="pmid6647119">{{Cite journal| author = Gauquelin G, Geelen G, Louis F, Allevard AM, Meunier C, Cuisinaud G, Benjanet S, Seidah NG, Chretien M, Legros JJ | title = Presence of vasopressin, oxytocin and neurophysin in the retina of mammals, effect of light and darkness, comparison with the neuropeptide content of the neurohypophysis and the pineal gland | journal = Peptides | volume = 4 | issue = 4 | pages = 509–15 | year = 1983 | pmid = 6647119 | doi = 10.1016/0196-9781(83)90056-6| url = | issn = }}</ref> the adrenal medulla,<ref name="pmid6699132">{{Cite journal| author = Ang VT, Jenkins JS | title = Neurohypophysial hormones in the adrenal medulla | journal = J. Clin. Endocrinol. Metab. | volume = 58 | issue = 4 | pages = 688–91 | year = 1984 | month = April | pmid = 6699132 | doi = 10.1210/jcem-58-4-688 | url = | issn = }}</ref> the placenta,<ref name="pmid6832059">{{Cite journal| author = Fields PA, Eldridge RK, Fuchs AR, Roberts RF, Fields MJ | title = Human placental and bovine corpora luteal oxytocin | journal = Endocrinology | volume = 112 | issue = 4 | pages = 1544–6 | year = 1983 | month = April | pmid = 6832059 | doi = 10.1210/endo-112-4-1544 | url = | issn = }}</ref> the thymus<ref name="pmid3961493">{{Cite journal| author = Geenen V, Legros JJ, Franchimont P, Baudrihaye M, Defresne MP, Boniver J | title = The neuroendocrine thymus: coexistence of oxytocin and neurophysin in the human thymus | journal = Science | volume = 232 | issue = 4749 | pages = 508–11 | year = 1986 | month = April | pmid = 3961493 | doi = 10.1126/science.3961493 | url = | issn = }}</ref> and the pancreas.<ref name="pmid3195625">{{Cite journal| author = Amico JA, Finn FM, Haldar J | title = Oxytocin and vasopressin are present in human and rat pancreas | journal = Am. J. Med. Sci. | volume = 296 | issue = 5 | pages = 303–7 | year = 1988 | month = November | pmid = 3195625 | doi = 10.1097/00000441-198811000-00003| url = http://journals.lww.com/amjmedsci/Fulltext/1988/11000/Oxytocin_and_Vasopressin_Are_Present_in_Human_and.3.aspx | issn = }}</ref> The finding of significant amounts of this classically "neurohypophysial" hormone outside the central nervous system raises many questions regarding its possible importance in these different tissues.
|monitoring=* There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.


====Female====
<!--IV Compatibility-->
Oxytocin is synthesized by [[corpora lutea]] of several species, including ruminants and primates. Along with estrogen, it is involved in inducing the endometrial synthesis of [[prostaglandin F2alpha|prostaglandin F<sub></sub>]] to cause regression of the corpus luteum.
|IVCompat=* There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.


====Male====
<!--Overdosage-->
The [[Leydig cells]] in some species have also been shown to possess the biosynthetic machinery to manufacture testicular oxytocin ''de novo'', specifically, in rats (who can synthesize [[Vitamin C]] endogenously), and in guinea pigs who (like humans) require an exogenous source of vitamin C ([[ascorbate]]) in their diets.<ref name="pmid1456839">{{Cite journal| author = Kukucka Mark A, Misra Hara P | title = HPLC determination of an oxytocin-like peptide produced by isolated guinea pig Leydig cells: stimulation by ascorbate | journal = Arch. Androl. | volume = 29 | issue = 2 | pages = 185–90 | year = 1992 | pmid = 1456839 | doi = 10.3109/01485019208987723 | url = http://informahealthcare.com/doi/abs/10.3109/01485019208987723 | issn = }}</ref>
|overdose=* Overdosage with oxytocin injection (synthetic) depends essentially on uterine hyperactivity whether or not due to hypersensitivity to this agent.  Hyperstimulation with strong (hypertonic) or prolonged (tetanic) contractions, or a resting tone of 15 to 20 mm H2O or more between contractions can lead to tumultuous labor, [[uterine rupture]], cervical and vaginal lacerations, [[postpartum hemorrhage]], [[uteroplacental hypoperfusion]] and variable deceleration of fetal heart, [[fetal hypoxia]], [[hypercapnia]] or death. Water intoxication with convulsions, which is caused by the inherent antidiuretic effect of oxytocin, is a serious complication that may occur if large doses (40 to 50 milliunits/minute) are infused for long periods. Management consists of immediate discontinuation of oxytocin, and symptomatic and supportive therapy.
|drugBox=[[File:Oxytocin wiki.png|600px|thumbnail|left]]
{{clear}}
|mechAction=* Oxytocin injection (synthetic) acts on the smooth muscle of the uterus to stimulate contractions; response depends on the uterine threshold of excitability.  It exerts a selective action on the smooth musculature of the uterus, particularly toward the end of pregnancy, during labor and immediately following delivery.  Oxytocin stimulates rhythmic contractions of the uterus, increases the frequency of existing contractions and raises the tone of the uterine musculature.  Synthetic oxytocin does not possess the cardiovascular effects, such as elevation of blood pressure, as exhibited by vasopressin found in posterior pituitary injection.
|structure=* Each mL of Oxytocin Injection, USP (synthetic), intended for intravenous infusion or intramuscular injection, possesses an oxytocic activity equivalent to 10 USP Oxytocin Units and contains chlorobutanol anhydrous (chloral derivative) 0.5%.  This product may contain up to 12.5% decomposition products/impurities.  Oxytocin injection (synthetic) is a sterile, clear, colorless solution of oxytocin in Water for Injection prepared by synthesis.  Acetic acid may have been added for pH adjustment (pH 3.0-5.0). The structural formula is:


==Structure and relation to vasopressin==
[[File:Oxytocin structure.jpg|600px|thumbnail|left]]
Oxytocin is a [[peptide]] of nine [[amino acid]]s (a nonapeptide). The sequence is [[cysteine|cys]] – [[tyrosine|tyr]] – [[isoleucine|ile]] – [[glutamine|gln]] – [[asparagine|asn]] – [[cysteine|cys]] – [[proline|pro]] – [[leucine|leu]] – [[glycine|gly]] - NH<sub>2</sub> (CYIQNCPLG-NH<sub>2</sub>). The cysteine residues form a [[sulfur bridge]]. Oxytocin has a [[molecular mass]] of 1007 [[dalton (unit)|dalton]]s. One [[international unit]] (IU) of oxytocin is the equivalent of about 2 [[microgram]]s of pure peptide.
{{clear}}
|PD=* There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.


The biologically active form of oxytocin, commonly measured by [[Radioimmunoassay|RIA]] and/or [[HPLC]] techniques, is also known as the octapeptide "oxytocin disulfide" (oxidized form), but oxytocin also exists as a reduced dithiol nonapeptide called oxytoceine.<ref>{{Cite journal| author = du Vigneaud V. | title = Experiences in the Polypeptide Field: Insulin to Oxytocin | journal = Ann. NY Acad. Sci. | volume = 88 | issue = 3 | pages = 537–48 | year = 1960 | pmid =  | doi = 10.1111/j.1749-6632.1960.tb20052.x | url = http://www3.interscience.wiley.com/journal/119764459/abstract | issn = }}</ref> It has been theorized that open chain oxytoceine (the reduced form of oxytocin) may also act as a free radical scavenger (by donating an electron to a free radical); oxytoceine may then be oxidized back to oxytocin via the redox potential of [[dehydroascorbate]] <---> [[ascorbate]].<ref name="DLA: Mechanisms by which hypoxia augments Leydig cell viability and differentiated cell function in vitro">{{Cite web| url=http://scholar.lib.vt.edu/theses/available/etd-06062008-170416 | title=Mechanisms by which hypoxia augments Leydig cell viability and differentiated cell function in vitro | last=Kukucka | first=Mark A. | date=1993-04-18 | publisher=Digital Library and Archives | accessdate=2010-02-21}}</ref>
<!--Pharmacokinetics-->
|PK=* There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.


[[File:Oxytocin-neurophysin.png|thumb|240px|left|Oxytocin (ball-and-stick) bound to its carrier protein neurophysin (ribbons)]]
<!--Nonclinical Toxicology-->
The structure of oxytocin is very similar to that of [[vasopressin]] ([[cysteine]] – [[tyrosine]] – <u>[[phenylalanine|phe]]</u> – [[glutamine|gln]] – [[asparagine|asn]] – [[cysteine|cys]] – [[proline|pro]] – <u>[[arginine|arg]]</u> – [[glycine|gly]]-NH<sub>2</sub>), also a [[nonapeptide]] with a sulfur bridge, whose sequence differs from oxytocin by 2 amino acids. A table showing the sequences of members of the vasopressin/oxytocin superfamily and the species expressing them is present in the [[vasopressin]] article. Oxytocin and vasopressin were isolated and synthesized by [[Vincent du Vigneaud]] in 1953, work for which he received the [[Nobel Prize in Chemistry]] in 1955.
|nonClinToxic='''Carcinogenesis, Mutagenesis, Impairment of Fertility'''
*There are no animal or human studies on the carcinogenicity and mutagenicity of this drug, nor is there any information on its effect on fertility.
|clinicalStudies=*There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.


Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including [[corticotropin-releasing hormone]] (CRH) and [[dynorphin]], for example, that act locally. The magnocellular neurons that make oxytocin are adjacent to magnocellular neurons that make vasopressin, and are similar in many respects.
<!--How Supplied-->
|howSupplied=[[File:Oxytocin how supplied.png|600px|thumbnail|left]]
{{clear}}


<!-- The last paragraph should be expanded upon or deleted. It is relevant enough to remain(though only because of previous referrences to vasopressin), but that it says "and are similar in several respects" and does not give a refference or attempt to explain itself is unacceptable. This "fact" may be sufficient for the creation of another article. -->
*Discard unused portion.


==Oxytocin receptor polymorphism==
*Use only if solution is clear and seal intact.
The [[oxytocin receptor]] in humans has several [[allele]]s, which differ in their effectiveness. Individuals [[homozygous]] for the "G" allele, when compared to carriers of the "A" allele, show higher [[empathy]], lower stress response,<ref>{{Cite journal|author=Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D |title=Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=106 |issue=50 |pages=21437–41 |year=2009 |month=December |pmid=19934046 |doi=10.1073/pnas.0909579106 |pmc=2795557}}</ref> as well as lower prevalence of [[autism]] and of poor parenting skills.<ref>{{Cite news
|storage=* Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
| last = Angier
| first = Natalie
| title = The Biology Behind the Milk of Human Kindness
| work = The New York Times
| date = 2009-11-24
| url = http://www.nytimes.com/2009/11/24/science/24angier.html
}}</ref>


==Evolution==
* Do not permit to freeze.
Virtually all [[vertebrate]]s have an oxytocin-like [[nonapeptide]] hormone that supports reproductive functions and a vasopressin-like nonapeptide hormone involved in water regulation. The two genes are usually located close to each other (less than 15,000 bases apart) on the same [[chromosome]] and are transcribed in opposite directions (however, in [[fugu]],<ref name="pmid9356472">{{Cite journal|doi=10.1073/pnas.94.23.12462 |author=Venkatesh B, Si-Hoe SL, Murphy D, Brenner S |title=Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=94 |issue=23 |pages=12462–6 |year=1997 |month=November |pmid=9356472 |pmc=25001 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=9356472}}</ref> the homologs are further apart and transcribed in the same directions).
|packLabel=[[File:Oxytocin pdp 1.jpg|600px|thumbnail|left]]
{{clear}}


It is thought that the two genes resulted from a [[gene duplication]] event; the ancestral gene is estimated to be about 500 million years old and is found in [[cyclostome]]s{{dn}} (modern members of the [[Agnatha]]).<ref name="Gimpl" />
[[File:Oxytocin pdp 2.jpg|600px|thumbnail|left]]
{{clear}}


==Industrial use of drug==
[[File:Oxytocin label.png|600px|thumbnail|left]]
Oxytocin can be administered to bovine animals in order to increase the production of dairy milk.
{{clear}}
|fdaPatientInfo=* There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.


==Misuse of drug==
<!--Precautions with Alcohol-->
Reports exist of hundreds of girls being kidnapped from across [[India]] and brought to Sodhawas and Geerwar villages in [[Alwar district]] of [[Rajasthan]], where they are given oxytocin injections to hasten their puberty and pushed into [[prostitution]]. The kidnapped girls have reportedly been as young as six-month-old babies. They are raised by the villagers as their own daughters.<ref>{{Cite journal|last1=Bhalla |first1=Abhishek  |last2=Choudhry |first2=Preeti |year=2010 |title=Girls drugged into puberty, sold as prostitutes |journal=[[India Today]] |publisher=India Today group |volume= |issue=May 27, 2010 |pages= |url=http://indiatoday.intoday.in/site/Story/99132/120/Drugged+into+puberty,+sold+for+sex.html |doi= }}</ref>
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.


==See also==
<!--Brand Names-->
* [[Carbetocin]]
|brandNames=Pitocin
* [[Demoxytocin]]
|lookAlike=
* [[WAY-267,464]]


==References==
<!--Drug Shortage Status-->
{{Reflist|2}}
|drugShortage=
}}
{{PillImage
|fileName=No image.jpg
}}
{{LabelImage
|fileName={{PAGENAME}}11.png
}}
{{LabelImage
|fileName={{PAGENAME}}11.png
}}
<!--Pill Image-->


==Further reading==
{{Refbegin}}
*{{Cite journal|author=Lee HJ, Macbeth AH, Pagani JH, Young WS |title=Oxytocin: the great facilitator of life |journal=Progress in Neurobiology |volume=88 |issue=2 |pages=127–51 |year=2009 |month=June |pmid=19482229 |doi=10.1016/j.pneurobio.2009.04.001 |pmc=2689929}}
* {{Cite book| author =  Caldwell HK, Young WS III | authorlink = | editor = Abel L, Lim R| others = | title = Handbook of neurochemistry and molecular neurobiology | edition = | language = | publisher = Springer | location = Berlin | year = 2006 | origyear = | pages = 573–607 | quote = | isbn = 0-387-30348-0 | oclc = | doi = | url = http://refworks.springer.com/mrw/fileadmin/pdf/Neurochemistry/0387303480C25.PDF | accessdate = | chapter = Oxytocin and Vasopressin: Genetics and Behavioral Implications }}
{{Refend}}




<!--Label Display Image-->


{{Hormones}}
{{Anxiolytics}}
{{Oxytocics}}
{{Pituitary and hypothalamic hormones and analogues}}
{{Neuropeptide agonists and antagonists}}
{{Neuropeptides}}
{{Neurotransmitters}}
{{Other gynecologicals}}


[[Category:Drugs]]
 
 
 
<!--Category-->
 
[[Category:Drug]]
[[Category:Neuropeptides]]
[[Category:Neuropeptides]]
[[Category:Obstetrics]]
[[Category:Neuroscience]]
[[Category:Neuroscience]]
[[Category:Neurotransmitters]]
[[Category:Neurotransmitters]]
[[Category:Posterior pituitary hormones]]
[[Category:Posterior pituitary hormones]]
[[Category:Interpersonal chemistry]]
[[Category:Breastfeeding]]
[[ar:أوكسيتوسين]]
[[be-x-old:Аксытацын]]
[[bs:Oksitocin]]
[[bg:Окситоцин]]
[[ca:Oxitocina]]
[[cs:Oxytocin]]
[[da:Oxytocin]]
[[de:Oxytocin]]
[[dv:އޮކްސިޓޯސިން]]
[[et:Oksütotsiin]]
[[es:Oxitocina]]
[[eu:Oxitozina]]
[[fa:اکسی‌توسین]]
[[fr:Ocytocine]]
[[ko:옥시토신]]
[[hi:ऑक्सीटॉसिन]]
[[hr:Oksitocin]]
[[id:Oksitosin]]
[[is:Oxytósín]]
[[it:Ossitocina]]
[[he:אוקסיטוצין]]
[[kn:ಆಕ್ಸಿಟೋಸಿನ್‌]]
[[lt:Oksitocinas]]
[[hu:Oxitocin]]
[[mk:Окситоцин]]
[[nl:Oxytocine]]
[[ja:オキシトシン]]
[[no:Oksytocin]]
[[pl:Oksytocyna]]
[[pt:Ocitocina]]
[[ru:Окситоцин]]
[[sq:Oksitocina]]
[[sk:Oxytocín]]
[[sr:Окситоцин]]
[[sh:Oksitocin]]
[[fi:Oksitosiini]]
[[sv:Oxytocin]]
[[ta:ஆக்சிடாசின்]]
[[te:ఆక్సిటోసిన్]]
[[uk:Окситоцин]]
[[zh:催生素]]

Revision as of 13:45, 9 March 2015

Oxytocin
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]

Disclaimer

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Overview

Oxytocin is a reproductive control agent that is FDA approved for the treatment of incomplete or inevitable abortion, control of postpartum uterine bleeding, induction or stimulation of labor. Common adverse reactions include nausea and vomiting.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Induction of labor, Medically indicated
  • Oxytocin injection (synthetic) is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable, in order to achieve early vaginal delivery for fetal or maternal reasons. It is indicated for (1) induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, pre-eclampsia at or near term, when delivery is in the best interest of mother and fetus or when membranes are prematurely ruptured and delivery is indicated; (2) stimulation or reinforcement of labor, as in selected cases of uterine inertia;
  • Dosing Information
  • Dosage of oxytocin is determined by uterine response. The following dosage information is based upon the various regimens and indications in general use.
  • Intravenous infusion (drip method) is the only acceptable method of administration for the induction or stimulation of labor.
  • Accurate control of the rate of infusion flow is essential. An infusion pump or other such device and frequent monitoring of strength of contractions and fetal heart rate are necessary for the safe administration of oxytocin for the induction or stimulation of labor. If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane.
  • An intravenous infusion of a non-oxytocin containing solution should be started. Physiologic electrolyte solutions should be used except under unusual circumstances.
  • To prepare the usual solution for intravenous infusion–one mL (10 units) is combined aseptically with 1,000 mL of a non-hydrating diluent.
  • The combined solution, rotated in the infusion bottle to insure thorough mixing, contains 10 mU/mL. Add the container with dilute oxytocic solution to the system through the use of a constant infusion pump or other such device to control accurately the rate of infusion.
  • The initial dose should be no more than 1 to 2 mU/min. The dose may be gradually increased in increments of no more than 1 to 2 mU/min., until a contraction pattern has been established which is similar to normal labor.
  • The fetal heart rate, resting uterine tone, and the frequency, duration, and force of contractions should be monitored.
  • The oxytocin infusion should be discontinued immediately in the event of uterine hyperactivity or fetal distress. Oxygen should be administered to the mother. The mother and fetus must be evaluated by the responsible physician.
Control of Postpartum Uterine Bleeding
  • Oxytocin injection (synthetic) is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.
  • Dosing Information
  • Intravenous Infusion (Drip Method)—To control postpartum bleeding, 10 to 40 units of oxytocin may be added to 1,000 mL of a nonhydrating diluent and run at a rate necessary to control uterine atony.
  • Intramuscular Administration—1 mL (10 units) of oxytocin can be given after delivery of the placenta.

Treatment of Incomplete or Inevitable Abortion

  • It is indicated for adjunctive therapy in the management of incomplete or inevitable abortion. In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases.
  • Dosing Information
  • Intravenous infusion with physiologic saline solution, 500 mL, or 5% dextrose in physiologic saline solution to which 10 units of oxytocin have been added should be infused at a rate of 20 to 40 drops/minute.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

  • There is limited information regarding Off-Label Guideline-Supported Use of Oxytocin in adult patients.

Non–Guideline-Supported Use

  • There is limited information regarding Off-Label Non–Guideline-Supported Use of Oxytocin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

  • There is limited information regarding FDA-Labeled Use of Oxytocin in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

  • There is limited information regarding Off-Label Guideline-Supported Use of Oxytocin in pediatric patients.

Non–Guideline-Supported Use

  • There is limited information regarding Off-Label Non–Guideline-Supported Use of Oxytocin in pediatric patients.

Contraindications

Oxytocin injection (synthetic) is contraindicated in any of the following conditions:

  • Significant cephalopelvic disproportion;
  • Unfavorable fetal positions or presentations which are undeliverable without conversion prior to delivery, i.e., transverse lies;
  • In obstetrical emergencies where the benefit-to-risk ratio for either the fetus or the mother favors surgical intervention;
  • In cases of fetal distress where delivery is not imminent;
  • Prolonged use in uterine inertia or severe toxemia;
  • Hypertonic uterine patterns;
  • Patients with hypersensitivity to the drug;
  • Induction or augmentation of labor in those cases where vaginal delivery is contraindicated, such as cord presentation or prolapse, total placenta previa, and vasa previa.

Warnings

  • Oxytocin injection (synthetic) when given for induction or stimulation of labor, must be administered only by the intravenous route and with adequate medical supervision in a hospital.

PRECAUTIONS

General

  • All patients receiving intravenous oxytocin must be under continuous observation by trained personnel with a thorough knowledge of the drug and qualified to identify complications. A physician qualified to manage any complications should be immediately available.
  • When properly administered, oxytocin should stimulate uterine contractions similar to those seen in normal labor. Overstimulation of the uterus by improper administration can be hazardous to both mother and fetus. Even with proper administration and adequate supervision, hypertonic contractions can occur in patients whose uteri are hypersensitive to oxytocin.
  • Except in unusual circumstances, oxytocin should not be administered in the following conditions: prematurity, borderline cephalopelvic disproportion, previous major surgery on the cervix or uterus including caesarean section, overdistention of the uterus, grand multiparity or invasive cervical carcinoma. Because of the variability of the combinations of factors which may be present in the conditions above, the definition of ‘‘unusual circumstances’’ must be left to the judgement of the physician. The decision can only be made by carefully weighing the potential benefits which oxytocin can provide in a given case against rare but definite potential for the drug to produce hypertonicity or tetanic spasm.
  • Maternal deaths due to hypertensive episodes, subarachnoid hemorrhage, rupture of the uterus and fetal deaths due to various causes have been reported associated with the use of parenteral oxytocic drugs for induction of labor and for augmentation in the first and second stages of labor.
  • Oxytocin has been shown to have an intrinsic antidiuretic effect, acting to increase water reabsorption from the glomerular filtrate. Consideration should, therefore, be given to the possibility of water intoxication, particularly when oxytocin is administered continuously by infusion and the patient is receiving fluids by mouth.

Adverse Reactions

Clinical Trials Experience

  • The following adverse reactions have been reported in the mother:
  • The possibility of increased blood loss and afibrinogenemia should be kept in mind when administering the drug.
  • Severe water intoxication with convulsions and coma has occurred, and is associated with a slow oxytocin infusion over a 24-hour period. Maternal death due to oxytocin-induced water intoxication has been reported.
  • The following adverse reactions have been reported in the fetus or infant:
  • Due to induced uterine mobility:


  • Due to use of oxytocin in the mother:

Postmarketing Experience

  • There is limited information regarding Postmarketing Experience of Oxytocin in the drug label.

Drug Interactions

  • Severe hypertension has been reported when oxytocin was given three to four hours following prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia. Cyclopropane anesthesia may modify oxytocin’s cardiovascular effects, so as to produce unexpected results such as hypotension. Maternal sinus bradycardia with abnormal atrioventricular rhythms has also been noted when oxytocin was used concomitantly with cyclopropane anesthesia.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C Pregnancy Category C

  • There are no known indications for use of oxytocin in the first and second trimester of pregnancy other than in relation to spontaneous or induced abortion. Based on the wide experience with this drug and its chemical structure and pharmacological properties, it would not be expected to present a risk of fetal abnormalities when used as indicated.
  • Nonteratogenic Effects—See ADVERSE REACTIONS in the fetus or infant.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category
  • There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Oxytocin in women who are pregnant.

Labor and Delivery

Antepartum

  • Oxytocin injection (synthetic) is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable, in order to achieve early vaginal delivery for fetal or maternal reasons. It is indicated for (1) induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, pre-eclampsia at or near term, when delivery is in the best interest of mother and fetus or when membranes are prematurely ruptured and delivery is indicated; (2) stimulation or reinforcement of labor, as in selected cases of uterine inertia; (3) adjunctive therapy in the management of incomplete or inevitable abortion. In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases.

Postpartum

  • Oxytocin injection (synthetic) is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.

Nursing Mothers

  • It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when oxytocin is administered to a nursing woman.

Pediatric Use

  • There is no FDA guidance on the use of Oxytocin with respect to pediatric patients.

Geriatic Use

  • There is no FDA guidance on the use of Oxytocin with respect to geriatric patients.

Gender

  • There is no FDA guidance on the use of Oxytocin with respect to specific gender populations.

Race

  • There is no FDA guidance on the use of Oxytocin with respect to specific racial populations.

Renal Impairment

  • There is no FDA guidance on the use of Oxytocin in patients with renal impairment.

Hepatic Impairment

  • There is no FDA guidance on the use of Oxytocin in patients with hepatic impairment.

Females of Reproductive Potential and Males

  • There is no FDA guidance on the use of Oxytocin in women of reproductive potentials and males.

Immunocompromised Patients

  • There is no FDA guidance one the use of Oxytocin in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Dosage of oxytocin is determined by uterine response. The following dosage information is based upon the various regimens and indications in general use.

Induction or Stimulation of Labor

  • Intravenous infusion (drip method) is the only acceptable method of administration for the induction or stimulation of labor.
  • Accurate control of the rate of infusion flow is essential. An infusion pump or other such device and frequent monitoring of strength of contractions and fetal heart rate are necessary for the safe administration of oxytocin for the induction or stimulation of labor. If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane.
  • An intravenous infusion of a non-oxytocin containing solution should be started. Physiologic electrolyte solutions should be used except under unusual circumstances.
  • To prepare the usual solution for intravenous infusion–one mL (10 units) is combined aseptically with 1,000 mL of a non-hydrating diluent.
  • The combined solution, rotated in the infusion bottle to insure thorough mixing, contains 10 mU/mL. Add the container with dilute oxytocic solution to the system through the use of a constant infusion pump or other such device to control accurately the rate of infusion.
  • The initial dose should be no more than 1 to 2 mU/min. The dose may be gradually increased in increments of no more than 1 to 2 mU/min., until a contraction pattern has been established which is similar to normal labor.
  • The fetal heart rate, resting uterine tone, and the frequency, duration, and force of contractions should be monitored.
  • The oxytocin infusion should be discontinued immediately in the event of uterine hyperactivity or fetal distress. Oxygen should be administered to the mother. The mother and fetus must be evaluated by the responsible physician.

Control of Postpartum Uterine Bleeding


  • Intravenous Infusion (Drip Method)—To control postpartum bleeding, 10 to 40 units of oxytocin may be added to 1,000 mL of a nonhydrating diluent and run at a rate necessary to control uterine atony.
  • Intramuscular Administration—1 mL (10 units) of oxytocin can be given after delivery of the placenta.

Treatment of Incomplete or Inevitable Abortion

  • Intravenous infusion with physiologic saline solution, 500 mL, or 5% dextrose in physiologic saline solution to which 10 units of oxytocin have been added should be infused at a rate of 20 to 40 drops/minute.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Monitoring

  • There is limited information regarding Monitoring of Oxytocin in the drug label.

IV Compatibility

  • There is limited information regarding IV Compatibility of Oxytocin in the drug label.

Overdosage

  • Overdosage with oxytocin injection (synthetic) depends essentially on uterine hyperactivity whether or not due to hypersensitivity to this agent. Hyperstimulation with strong (hypertonic) or prolonged (tetanic) contractions, or a resting tone of 15 to 20 mm H2O or more between contractions can lead to tumultuous labor, uterine rupture, cervical and vaginal lacerations, postpartum hemorrhage, uteroplacental hypoperfusion and variable deceleration of fetal heart, fetal hypoxia, hypercapnia or death. Water intoxication with convulsions, which is caused by the inherent antidiuretic effect of oxytocin, is a serious complication that may occur if large doses (40 to 50 milliunits/minute) are infused for long periods. Management consists of immediate discontinuation of oxytocin, and symptomatic and supportive therapy.

Pharmacology

Mechanism of Action

  • Oxytocin injection (synthetic) acts on the smooth muscle of the uterus to stimulate contractions; response depends on the uterine threshold of excitability. It exerts a selective action on the smooth musculature of the uterus, particularly toward the end of pregnancy, during labor and immediately following delivery. Oxytocin stimulates rhythmic contractions of the uterus, increases the frequency of existing contractions and raises the tone of the uterine musculature. Synthetic oxytocin does not possess the cardiovascular effects, such as elevation of blood pressure, as exhibited by vasopressin found in posterior pituitary injection.

Structure

  • Each mL of Oxytocin Injection, USP (synthetic), intended for intravenous infusion or intramuscular injection, possesses an oxytocic activity equivalent to 10 USP Oxytocin Units and contains chlorobutanol anhydrous (chloral derivative) 0.5%. This product may contain up to 12.5% decomposition products/impurities. Oxytocin injection (synthetic) is a sterile, clear, colorless solution of oxytocin in Water for Injection prepared by synthesis. Acetic acid may have been added for pH adjustment (pH 3.0-5.0). The structural formula is:

Pharmacodynamics

  • There is limited information regarding Pharmacodynamics of Oxytocin in the drug label.

Pharmacokinetics

  • There is limited information regarding Pharmacokinetics of Oxytocin in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

  • There are no animal or human studies on the carcinogenicity and mutagenicity of this drug, nor is there any information on its effect on fertility.

Clinical Studies

  • There is limited information regarding Clinical Studies of Oxytocin in the drug label.

How Supplied

  • Discard unused portion.
  • Use only if solution is clear and seal intact.

Storage

  • Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
  • Do not permit to freeze.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

  • There is limited information regarding Patient Counseling Information of Oxytocin in the drug label.

Precautions with Alcohol

  • Alcohol-Oxytocin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Pitocin

Look-Alike Drug Names

There is limited information regarding Oxytocin Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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