The administration of oxytocic drugs during caesarean section is an important intervention to prevent uterine atony or treat established postpartum hemorrhage. Considerable past and current research has shown that these agents have a narrow therapeutic range. A detailed knowledge by anesthetists of optimal doses and side effects is therefore required. Oxytocin remains the first line agent. In view of receptor desensitization, second line agents may be required, namely ergot alkaloids and prostaglandins. This review examines the adverse hemodynamic and side effects, and methods for their limitation. An approach to dosing and choices of agent for the limitation of postpartum hemorrhage is suggested.
Uterine atony, is a serious condition that can occur after childbirth. It occurs when the uterus fails to contract after the delivery of the baby, and it can lead to a potentially life-threatening condition known as postpartum hemorrhage .The objective of drugs are used to treat this condition and save the thousands life of children and mother. It was the life threaten many decades ago but the use of life saving drugs such as oxytocin,mesoprostol,prostaglandin, ergot alkaloids and carbetosin, syntometoine can save may live.
Every year 166 000 women die of obstetric hemorrhage and more than 50% of these deaths occur insub-Saharan Africa.1 Uterine atony is the commonestcause of severe postpartum hemorrhage (PPH), as tragically described by Hemingway. Consequently the administration of uterotonic drugs during caesarean section(CS) has become essential to diminish the risk ofPPH and improve maternal safety. These agents havea narrow therapeutic range in terms of maternal morbidity.The exact dose, route and rate of administrationare therefore important, as well as a detailed knowledgeof their pharmacology.Central to the mechanism of the contraction of uterinesmooth muscle during labour, which is enhanced bythe action of oxytocin, is the enzyme myosin light chainkinase (MLCK). Intracellular calcium, the levels ofwhich are controlled by voltage and receptor operatedchannels and by release from the sarcoplasmic reticulum,is bound to calmodulin and stimulates conversionof MLCK-P to MLCK, which in turn phosphorylatesmyosin and initiates smooth muscle contraction
Classification of drugs used in uterine atony:
I. Posterior pituitary hormone: Oxytocin, desamino oxytocin
II. Ergot alkaloids: Ergometrine, Methyl ergometrine
III. Prostaglandins: PGE2, PGF2A,pge1
General uses of drugs used in uterine atony:
I. Oxytocin causes the stimulants of contraction of uterine fundus.
II. It avoids postpartum hemorrhage.
III. It is also used for labour augmentation and induction.
IV. Prostaglandins cause the initiation of labour at term and also for pre term labours and enhances the contractions and ripening of cervix.
V. Ergot alkaloids induces titanic contraction of uterus.
VI. It causes contraction of uterus as a whole. (fundus and cervix)
Side effects of drugs used in uterine atony:
IV. Hypertension because of contraction of blood vessels
V. Vasoconstriction of peripheral blood vessels which leads to Gangrene.
Oxytocin is a peptide hormone and neuropeptide. Oxytocin is normally produced by the paraventricular nucleus of the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, sexual reproduction in both sexes, and during and after childbirth. Oxytocin is released into the bloodstream as a hormone in response to stretching of the cervixand uterus during labor and with stimulation of the nipples from breastfeeding.This helps with birth, bonding with the baby, and milk production. Oxytocin was discovered by Henry Dale in 1906. Its molecular structure was discovered in 1952. Oxytocin is also used as a medication to facilitate childbirth.
? What is it: oxytocin is a non-peptide hormone released in pulses from the posterior pituitary and is the basis of Syntocin and Syntocinon.
? Drug Indication: Used for labor induction, augmentation of labor, postpartum abbreviation of third stage of labor, postpartum control of uterine bleeding, termination of pregnancy and for the evaluation of fetal respiratory capability. Oxytocincannot be used for elective induction of labor, there must be a clear medical requirement.
? What does it do: It has a number of roles including stimulating contraction of myometrium and myo-epithelium of the mammary ducts, and influencing maternal behaviour.
? How does it act: Uterine motility depends on the formation of the contractile protein actomyosin under the influence of the Ca2+-dependent phosphorylating enzyme myosin light-chain kinase. Oxytocin promotes contractions by increasing the intracellular Ca2+, which in turn activates myosin’s light chain kinase.. Oxytocin has specific receptors in the muscle lining of the uterus and the receptor concentration increases greatly during pregnancy, reaching a maximum in early labor at term.
Activation of oxytocin receptors (OTR), in common with many other agonists, causes the activation of phospholipase-C ? (PLC?), which hydrolyses phosphatidylinositol bisphosphate (PIP2) leading to the formation of two second messengers: IP3 and diacylglycerol (DAG). Both messengers are thought to be involved in mediating the many cellular responses to oxytocin. IP3 stimulates calcium release from the SR, whilst DAG, the main activator of Protein Kinase C (PKC) may or may not affect myometrial tension. Using a variety of experimental approaches, we and others have shown that stimulation of Ca entry is the most prominent effect of oxytocin. Oxytocin also inhibits Ca efflux mechanisms. Oxytocin may also inhibit MLCP, slowing relaxation and enhancing force. Thus via a variety of mechanisms oxytocin has powerful stimulatory effects which have long been used clinically to aid parturition. During pregnancy, OTRs increase in number which is thought in part to underlie the increased sensitivity of the myometrium to oxytocin at term when little change in oxytocin levels can be detected. Antagonists to OTR have been developed as tocolytics and are discussed later.
? Clinical uses
The first clinical use of oxytocin was by Blair Bell in 1909, to stop post-partum haemorrhage. Oxytocin is now used widely in its synthetic forms, for labour augmentation and induction. Syntocin/Syntocinon is also administered during CS to cause a large contraction for stemming bleeding. Clinically, continuous iv infusion of oxytocin may not be optimal, as it does not replicate its natural pulsatile release and may also cause receptor desensitization and down regulation of OTR mRNA. Indeed, responses to administration of oxytocin are variable, and a pulsatile application of oxytocin has been shown to be more efficient than constant oxytocin infusion to induce labour. Even so it remains perplexing why up to 50% of women labouring poorly, do not respond to oxytocin administration and ultimately require CS, although difference in background acidity and lactate have recently been suggested. Thus dysfunctional labour remains a major contributor to the non-elective CS rate and oxytocin has not reduced this rate. More work is required to understand the causes of dysfunctional labour, so that they can either be prevented or remedied by additional agents.
Administration of oxytocin is not without risk; uterine hyperstimulation or rupture and foetal distress, Thefoetal distress arises as the over-contracted myometrium occludes blood vessels and diminishes placental perfusion. Thus the effects of administration of oxytocin in cases of poor/slow progress in the first stage of labour should always be carefully monitored and maximal doses, which are usually higher in primigravidae, not exceeded. In order to achieve successful labour induction with oxytocin, the cervix must be favourable.