202411022104

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Tags: pharmacology, Obstetrics

Oxytocin

Uterotonics
Commercially a/v oxytocin contains the preservative chlorbutol = negative inotrope

Structure and mechanism of action

Oxytocin is an endogenous neuropeptide hormone, with a nonapeptide structure, released by the posterior pituitary gland.
It exerts its main effects on uterine smooth muscle to cause contraction in labour and on the mammary glands to cause lactation

Oxytocin exerts its uterine effects by stimulation of oxytocin receptors in the myometrium. This causes direct myometrial contraction via phospholipase C activation and inositol triphosphate release, leading to the release of intracellular calcium.
It also stimulates the production of prostaglandin PGF2α and PGE2 in the endometrium, which help to initiate labour

Oxytocin receptor

The oxytocin receptor is a G-protein-coupled receptor. These receptors are known to exhibit receptor downregulation within a short time frame of exposure to the receptor agonist.
The receptors undergo rapid internalisation from the cell membrane due to this homologous stimulation.
This phenomenon has been demonstrated with the oxytocin receptor, in both in vitro and in vivo studies, in relation to endogenous as well as exogenously administered oxytocin

There is a decrease in the expression of oxytocin receptor messenger RNA (mRNA) and the binding sites of oxytocin, leading to reduced myometrial cell response and reduced contractions. The time frame within which this occurs may be relatively short

The majority of this research was undertaken by Balki and colleagues in Canada, who demonstrated that oxytocin receptor desensitisation occurs in both a concentration and time-dependent manner. As a result of this, oxytocin dose requirements in clinical practice vary depending on prior exposure.

Administration and pharmacokinetics

Synthetic oxytocin first came about in the 1950s and has since been exogenously administered for labour induction and labour augmentation, as well as for the prophylaxis and management of postpartum haemorrhage (PPH) in both vaginal and caesarean deliveries

The drug is stored in the fridge at a temperature of 2–8 °C and has a mean half-life of distribution of 2 min and an elimination half-life of 12 min

Both the liver and kidneys are involved in its rapid elimination, with very little being excreted in the urine
to further metabolise oxytocin, the placenta produces the enzyme oxytocinase which is released into the plasma, levels of which increase in pregnancy and peak at term. This enzyme metabolises both endogenous and synthetic oxytocin, therefore bolus doses need to be followed up with intravenous infusions to maintain the desired uterine contractile effects

C/I and SE

Cardiovascular

Oxytocin causes

Such changes are known to occur in fit and healthy women and are more prominent with rapid intravenous boluses

In healthy women undergoing CD, electrocardiography changes of ST depression and T-wave inversion were commonly seen. However, these effects were not attributed to the oxytocin bolus, but rather the sympathetic block of SA, surgery, pregnancy or delivery

The main absolute contraindication to oxytocin is true allergy.
Relative contraindications relate to its negative cardiovascular side effects, however modifications to the dosing regime allow it to be used even in women with severe cardiovascular disease.

Slower administration of oxytocin, co-administered with intravenous boluses or infusions of phenylephrine has been shown to mitigate the negative haemodynamic effects

Patients with preeclampsia and cardiac disease are at heightened risk for unpredictable and potentially severe cardiovascular and haemodynamic responses to oxytocin, mediated possibly by an inability to ↑ SV in the setting of diastolic dysfunction

Other side effects of oxytocin include

References