This document summarizes information about oxytocin, including its physiology, mechanism of action, pharmacodynamics, clinical uses, and adverse effects. Oxytocin is a hormone secreted by the posterior pituitary that acts on uterine smooth muscle, the mammary glands, and the brain. It is used clinically to induce and augment labor, prevent postpartum hemorrhage, and treat breast engorgement. While generally safe, oxytocin can cause uterine hyperstimulation and hypotension at high doses. Research continues to explore new oxytocin agonists and antagonists for clinical applications.

1. Submitted by HINNA HAMID
M Pharm 1st year (PHARMACOLOGY )
Department of Pharmaceutical sciences ,
UNIVERSITY OF KASHMIR,SRINAGAR.

2. Contents :-
 Introduction
 Physiology of Oxytocin
 Mechanism of action
 Pharmacodynamics
 Pharmacokinetics
 Oxytocin drugs and their clinical uses
 Adverse effects
 Contraindications
 Drug interactions and anaesthetic implications
 Oxytocin Agonists
 Oxytocin Antagonists
 Future Research
 Bibliography

3. Introduction :-
 Oxytocin is a nonapeptide secreted by the posterior
pituitary along with vasopressin (ADH).
 Also known as ‘cuddle hormone’ or the ‘love hormone’.
 Pituitary extract was first used in labour in 1909.
 Controversy as to whether the antidiuretic and uterine
stimulating activities were due to one substance or two
separate principles was finally resolved by du Vigneaud in
1953 when he separated Oxytocin and Vasopressin,
determined their chemical structure and synthesized them.
 Both are nonapeptides which differ at positions 3 and 8.

4. Source :-Posterior pituitary hormones By
Dr. William S. Messer, Jr., Professor of Medicinal and
Biological Chemistry at The University of Toledo.

5. Physiology of Oxytocin
 Oxytocin is synthesized as a larger
precursor in neurons whose cell
bodies reside in the paraventricular
nucleus and, to a lesser extent, the
supraoptic nucleus in the
hypothalamus.
 The precursor peptide is rapidly
cleaved to the active hormone and
its neurophysin, packaged into
secretory granules as an oxytocin-
neurophysin complex, and secreted
from nerve endings that terminate
primarily in the posterior pituitary
gland (neurohypophysis).
 Other sites of oxytocin synthesis
include the luteal cells of the ovary,
the endometrium, and the placenta,
but the physiologic significance of
this is not known.
https://www.slideshare.net/jincyannaiype/drugs-
acting-on-uterus

6. Mechanism of action
 Action of oxytocin on myometrium is independent of
innervation.
 There are specific G-protein coupled oxytocin receptors which
mediate the response mainly by depolarization of muscle fibres
and influx of Ca2+ ions as well as through phosphoinositide
hydrolysis and IP3 mediated intracellular release of Ca2+ ions.
 The number of oxytocin receptors increases markedly during
later part of pregnancy.
 Oxytocin increases PG synthesis and release by the
endometrium which may contribute to the contractile response.
 Distinct subtypes of oxytocin receptors have been shown on the
myometrium and the endometrium.

7. https://www.slideshare.net/jincyannaiype/dr
ugs-acting-on-uterus

8. https://www.slideshare.net/jincyannaiype/drugs-acting-on-
uterus

9.  Stimuli for oxytocin secretion include sensory stimuli
arising from dilation of the cervix and vagina and from
suckling at the breast.
 Increased oxytocin in maternal circulation is detected
in the second stage of labor, likely triggered by
sustained distension of the uterine cervix and vagina.
 Estradiol stimulates oxytocin secretion, whereas the
ovarian polypeptide relaxin inhibits its release. The
inhibitory effect of relaxin appears to be the net result
of a direct effect on oxytocin-producing cells and an
inhibitory action mediated indirectly by endogenous
opiates.

10. Pharmacodynamics :-
01. Uterus :-
 Oxytocin increases the force and frequency of uterine contractions.
 With low doses, full relaxation occurs inbetween contractions;basal
tone increases only with high doses.
 Increased contractility is due to hightened electrical activity of the
myometrial cell membrane— burst discharges are initiated and
accentuated.
 Estrogens sensitize the uterus to oxytocin; increase oxytocin receptors.
 Nonpregnant uterus and that during early pregnancy is rather resistant
to oxytocin; sensitivity increases progressively in the third trimester;
there is a sharp increase near term and quick fall during puerperium.
 Progestins decrease the sensitivity,but this effect is not marked in vivo.
 The increased contractility is restricted to the fundus and body; lower
segment is not contracted, may even be relaxed at term.

11. On pregnant uterus

13. On non pregnant uterus

14. 02 . Breast
 Oxytocin plays an important physiological role in milk
ejection.
 Stimulation of the breast through suckling or
mechanical manipulation induces oxytocin secretion,
causing contraction of the myoepithelium that
surrounds alveolar channels in the mammary gland.
 This action forces milk from the alveolar channels into
large collecting sinuses, where it is available to the
suckling infant.

16. 03 . CVS
 Conventional doses used in obstetrics have no effect
on BP but higher doses cause vasodilatation → brief
fall in BP, reflex tachycardia and flushing.
 This action is most marked in chicken—used for
bioassay. The umbilical vessels are markedly
constricted; oxytocin may help in their closure at birth.
04. Kidney
 Oxytocin in high doses exerts an ADH-like action—
urine output is decreased: pulmonary edema can occur
if large amounts of i.v. fluids and oxytocin are infused
together.
 Conventional doses are without any effect.

17. 05 . Brain
 Studies in rodents have implicated oxytocin as an
important CNS regulator of trust and of autonomic systems
linked to anxiety and fear, but its importance in humans in
this regard remains to be established.
 Brain regions proposed to be critical in the response to
fearful stimuli, including the amygdala, midbrain, and
striatum, showed decreased activation in response to
stressful stimuli following oxytocin treatment
(Baumgartner et al., 2008; Huber et al., 2005).
 The role of perturbations of oxytocin signaling in mental
conditions such as social phobia and autism and the
possible therapeutic benefit of drugs that manipulate CNS
oxytocin effects are exciting areas of ongoing investigation
(Romano et al., 2016).

18. PHARMACOKINETICS
 Being a peptide, oxytocin is inactive orally and is generally
administered by i.m. or i.v. routes, rarely by intranasal
spray.
 It is rapidly degraded in liver and kidney; plasma t½ ~6
min.
 Pregnant uterus and placenta elaborate a specific
aminopeptidase called oxytocinase—which can be detected
in maternal plasma.
Unitage and preparations:-
 1 IU of oxytocin = 2 μg of pure hormone.
 Commercially available oxytocin is produced synthetically.
OXYTOCIN, SYNTOCINON 2 IU/2 ml and 5 IU/ml inj.,
PITOCIN 5 IU/0.5 ml inj.

19. Oxytocin drugs
 Oxytocin is also known as Pitocin, Syntocinon, Ocytocin, Endopituitrina,
Oxitocina, Oxytocine, Oxytocinum, Oxytocic hormone and Orasthin.
 The commonly used drug types are pitocin and syntocinon, the chemical
resemblance to Oxytocin makes them an ideal drug of choice for various cases
for example at time if parturition .
 Pitocin is composed of oxtocic acid/ml along with chlorobutanol , a chloroform
derivative.
CLINICAL USES :-
Oxytocin is used therapeutically only to induce or augment labor and to treat or
prevent postpartum hemorrhage.
 Although widely used, oxytocin recently was added to a list of drugs “bearing a
heightened risk of harm.”
 In the U.S., the FDA-approved label contains this notice:
‘Elective induction of labor is defined as the initiation of labor in a pregnant
individual who has no medical indications for induction. Since the available data
are inadequate to evaluate the benefits- to-risks considerations, Pitocin is not
indicated for elective induction of labor’

20. 01.Induction of Labor
 Induction of labor is indicated when the perceived risk of
continued pregnancy to the mother or fetus exceeds the
risks of pharmacological induction.
 Oxytocin is the drug of choice for induction of labor for
women with a suitably ripened cervix
 It is administered by intravenous infusion of a diluted
solution, has a t1/2 of 12–15 min and achieves a steady-state
uterine response after about 30 min.
 Uterine hyperstimulation is an adverse effect of oxytocin
that should be avoided.
 Oxytocin at high doses activates the vasopressin V2
receptor and has antidiuretic effects. Vasodilating actions
of oxytocin also have been noted that may provoke
hypotension and reflex tachycardia.

21. 02.Augmentation of Dysfunctional
Labor
 Oxytocin also is used when spontaneous labor is not
progressing at an acceptable rate.
 To augment hypotonic contractions, an infusion rate of 10
mU/min typically is sufficient.
 As with labor induction, potential complications of uterine
overstimulation include trauma of the mother or fetus due
to forced passage through an incompletely dilated cervix,
uterine rupture, and compromised fetal oxygenation due to
decreased uterine perfusion.

22. 03.Prevention and Treatment of Postpartum
Hemorrhage
-Cesarean section
 Oxytocin (10 units IM) is given immediately after
delivery to help maintain uterine contractions and
tone.
 Alternatively, oxytocin (20 units) is diluted in 1 L of
intravenous solution (yielding a concentration of 20
mU/mL) and infused at a rate of 10 mU/min until the
uterus is contracted.
 The infusion rate then is reduced to 1–2 mU/min until
the mother is ready for transfer to the postpartum
unit.

23. 04. Breast engorgement
 It may occur due to inefficient milk ejection reflex—
oxytocin is effective only in such cases: an intranasal
spray may be given few minutes before suckling.
 It does not increase milk production.

24. 05.Oxytocin challenge test
 It is performed to determine utero-placental adequacy
in high risk pregnancies like in maternal diabetes
milletus and hypertension
 Oxytocin is infused i.v. at very low concentrations till
uterine contractions are elicited every 3–4 mins.

25. 06.Oxytocin deficiency:
 An impaired synthesis of Oxytocin would lead to Oxytocin
deficiency.
 Most common manifestation of Oxytocin deficiency would
be generalised depression and anxiety, sleep disturbances,
isolation and panic attacks.
 Oxytocin defiency is also said to be associated with
conditions like autism and schizophrenia.
 As Oxytocin plays a key role in establishing trust , falling in
love , parturition, mother – child bond etc recommended
doses when administered to autism patients are proven to
increase the sense of trust at the time of communication

26. Adverse effects :-
https://www.slideshare.net/minnup/dr-minnu-panditraos-oxytocics-tocolytics

27. Contraindications
 Significant cephalopelvic disproportion
 Unfavourable foetal positions
 Obstetric emergencies which favours surgery
 Hyperactive or hypertonic uterus
 When vaginal delivery is contraindicated,
 Anaphylactic patients
 Foetal distress
 Polyhydramnios
 Partial placenta pervia
 Elective labour induction

28. Drug interactions and anaesthetic
implications :-
https://www.slideshare.net/minnup/dr-minnu-panditraos-oxytocics-tocolytics

29. Desamino-oxytocin
 It has been developed as a buccal formulation; action
is similar to injected oxytocin, but less consistent.
 Its indications are:
Induction of labour: 50 IU buccal tablet repeated every
30min, max 10 tabs.
Uterine inertia: 25 IU every 30 min.
Promotion of uterine involution 25–50 IU 5 times daily
for 7 days.
Breast engorgement 25–50 IU just before breast
feeding.

30. Oxytocin Agonists
 OTR agonist molecules have been developed and studied as
pharmacological tools or as potential drugs for the management
of neuropsychiatric diseases including anxiety-related disorders,
schizophrenia, and autism.
 Synthetic oxytocin is used to augment labor and treat
postpartum hemorrhage.
 Demoxytocin is an oxytocin analogue that has been used for
labor induction, though it has been proven less effective
compared to prostaglandins
 Carbetocin (in trail phase)is a newer peptide synthetic
oxytocin analogue indicated for the prevention of uterine atony
(84-94% success rate) after cesarean section with spinal or
epidural anesthesia: it has a longer half-life(45min) than
oxytocin and possesses the advantage that it is administered in a
single dose, intramuscularly or intravenously

31. Oxytocin Antagonists as Tocolytic Agents
 The therapeutic target in the treatment of preterm labor is
currently the pharmacological inhibition of uterine
contractions with the use of various tocolytic agents.
 Tocolytic agents are used to maintain pregnancy for 24–48
hours to allow corticosteroids administration to act and to
permit the transfer of the mother to a center with a
neonatal intensive care unit.
 Selective human oxytocin receptors antagonists have also
been synthesized as tocolytic agents for the management of
preterm labor.

32. Peptide OTR Antagonists.
 Atosiban is an oxytocin analogue (1-Deamino-2-D-
Tyr-(O-ethyl)-4-Thr-8-ornoxytocin) based on
modification of some amino acids in the structure of
oxytocin at positions 1, 2, 4, and 8.
Source :- International Journal of Endocrinology

33.  It is a mixed vasopressin (V1a) and oxytocin receptor
antagonist that blocks OT binding to OTR and is the only
oxytocin antagonist used today for the treatment of preterm
labor in Europe and other countries, though not in the USA.
 However, as it is also an antagonist of the vasopressin receptor
V1a, this results in related undesirable effects.
 The onset of uterine relaxation after atosiban administration is
rapid.
 Atosiban is given intravenously for up to 48 hours.
 Clinically, atosiban is as effective as β2- adrenergic agonists and
with lesser adverse effects.
 When subcutaneously administered as maintenance therapy
after a period of preterm labor, atosiban failed to reduce the
incidence of preterm birth or improve neonatal outcome

34.  Barusiban is a selective peptide oxytocin antagonist
with a high affinity for the human OTR and low for the
V1a receptor.
 It has a higher potency and a longer duration of action
than atosiban.
 In contractility studies with isolated human
myometrium, barusiban inhibits oxytocininduced
myometrial contractions of both preterm and term
myometrium, and this action was at least as potent as
the action of atosiban.

35. Nonpeptide OTR Antagonists
 Since peptide antagonists lack oral bioavailability,
pharmaceutical companies have searched for an
effective nonpeptide oxytocin antagonist.
 GSK221149A (2-methyl-1,3-oxazol-4-yl morpholine
amide derivative 74), known as retosiban, is such a
nonpeptide oxytocin antagonist.
 Retosiban is 15-fold more potent compared to atosiban
for the OTR; it is at present on a Phase ll Clinical trial
investigating its action as a tocolytic, but the results
have not as yet been published

36. Source :- International Journal of Endocrinology

37. Future research:-
 Recent work has linked oxytocin in humans to creative cognition-the
ability to produce insights, ideas, and problem solutions that are
original and potentially useful
 To date, research has primarily attempted to establish functional
effects through measuring altered endogenous concentrations,
observing effects of exogenous administration and by investigating the
effects of polymorphisms and epigenetic modifications of the oxytocin
receptor gene.
 Current translational findings, particularly in the context of
therapeutic outcomes of intranasal oxytocin administration in autism
and schizophrenia. These clinical findings while somewhat varied in
outcome do offer increasing cause for optimism that targeting the
oxytocin system may provide a successful therapeutic approach for
social dysfunction. However, future research needs to focus on the
most effective treatment strategy and which types of individuals are
likely to benefit most.

38. Bibliography :-
 Goodman & Gillman’s - The pharmacological basis of Therapeutics,
13th Edition, By Laurence L. Brunton, Page no. 783-785
 Essentials of Medical Pharmacology, Sixth Edition By KD TRIPATHI,Page no.
319-324
 Basic & Clinical Pharmacology, 14th Edition By Bertram G. Katzung, Page no.
680-681
 Principles of Pharmacolgy, 3rd Edition By H L Sharma and K K Sharma,Page
no. 590-594.
 Oxytocics and tocolytics Available at :-https://www.slideshare.net/minnup/dr-
minnu-panditraos-oxytocics-tocolytics
 https://www.slideshare.net/jincyannaiype/drugs-acting-on-uterus

39.  ‘International Journal of Endocrinology’ Review Article :- The
Oxytocin-Oxytocin Receptor System and Its Antagonists as Tocolytic
Agents By Nikolaos Vrachnis,1 FotodotisM.Malamas,2 Stavros Sifakis,3
Efthymios Deligeoroglou,1 and Zoe Iliodromiti1
Available at :- doi:10.1155/2011/350546
 Pharmacological Role of Oxytocin – A Short Review By Anirudha
kabilan
 Oxytocin Lecture By Danish Hassan : Lecturer at University of
Sargodha.
https://www.slideshare.net/taimooratif/oxytocin-52840481
 Oxytocin presentation
Available at :-
https://www.slideshare.net/AYEBAZIBWEJEFF/oxytocin-final

40.  Oxytocin enables novelty seeking and creative performance through
upregulated approach: Evidence and avenues for future research By
Carsten K W De Dreu, Matthijs Baas and Nathalie Boot
 Overview of Human Oxytocin Research. By Kendrick KM1, Guastella
AJ2,3, Becker B4.
Available at :- doi: 10.1007/7854_2017_19