Oxytocin antagonists

Although there is no good evidence for an increase in circulating concentrations of oxytocin in either term or preterm labour, both term and preterm labour are associated with an increase in the expression of the oxytocin receptor in the myometrium and oxytocin is synthesized within the uterus itself, in both the myometrium and the decidua. This has led to the exploration of drugs which antagonize the oxytocin receptor as tocolytics. At the time of writing no specific oxytocin antagonist is available for clinical use. However atosiban, which is principally an Arginine vasopressin (AVP) receptor antagonists but also binds the oxytocin receptor at appropriate therapeutic concentrations, has a European licence for the treatment of preterm labour. Atosiban has been the subject of both placebo comparison trials and comparisons with sympath-omimetic drugs. The placebo-controlled trials undertaken in the USA were, to a certain extent, flawed in that randomization at early gestational ages was skewed resulting in an increase in neonatal deaths among very preterm babies whose mothers were treated with atosiban. The primary outcome of the placebo-controlled trial (which was the time between the initiation of treatment and therapeutic failure defined as either preterm delivery or the need for an alternate tocolytic) showed that atosiban was no better than placebo. There were, however, statistically significant differences in the number of women who remained undelivered and did not require an alternative tocolytic at the specific 24 and 48 h and 7 day time points. As with all previous trials of tocolytic drugs, this trial was complicated by a very high placebo response rate. Analysis of the data shows that at, for example, 48 h, although 70% of women randomized to receive atosiban appeared to respond to it, in reality the majority of these represent placebo responses and that in fact only 11% had a genuine clinical response. This represents one quarter of those women who were

Atosiban nonresponders

Apparent responses to Atosiban

rs7i

rs7i

Placebo nonresponders

Placebo responders

Genuine responses to Atosiban

Patients who require -

treatment

Patients who are not in preterm labour

Fig. 21.4 Analysis of the 48 hours outcome data from the placebo controlled trial of atosiban (Romero et al, Am J Obstet Gynecol (2000) 182(5): 1173-83). Of all patients allocated to atosiban treatment only 11% showed a genuine clinical response, which represents one quarter of those with the potential to benefit.

genuinely in preterm labour and had a potential to have a genuine clinical response (Fig. 21.4).

Trials comparing atosiban with sympathomimetic drugs showed equal clinical efficacy to beta-sympathomimetics but with atosiban having a dramatically improved maternal side-effect profile. The clinical response rate to either atosiban or sympathomimetic drugs in those trials was, however, so high (over 90%) that it is probable that the majority of patients enrolled in the study were not genuinely in preterm labour. Neither the placebo-controlled trial nor the sympathomimetic comparison trials demonstrated any improvement in any aspect of neonatal morbidity or in neonatal mortality associated with the use of atosiban.

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Getting Back Into Shape After The Pregnancy

Getting Back Into Shape After The Pregnancy

Once your pregnancy is over and done with, your baby is happily in your arms, and youre headed back home from the hospital, youll begin to realize that things have only just begun. Over the next few days, weeks, and months, youre going to increasingly notice that your entire life has changed in more ways than you could ever imagine.

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