Oxytocin Richter Mechanism of Action

Pharmacotherapeutic group: Systemic hormonal preparations, excl. sex hormones and insulins, Posterior pituitary lobe hormones, Oxytocin and analogues. ATC code: H01BB02.
Pharmacology: Pharmacodynamics: The pharmacological and clinical properties of oxytocin are identical to the natural hormone that is stored in the posterior lobe of the pituitary gland and released into the systemic circulation in response to suckling and labour.
The uterine myometrium contains receptors specific to oxytocin, which belong to the superfamily of G-protein-linked receptors. Oxytocin stimulates contraction of uterine smooth muscle more powerfully towards the end of pregnancy, during labour, and immediately postpartum. At these times, the oxytocin receptors in the myometrium are increased. Activation of receptors by oxytocin increases intracellular calcium concentrations by triggering its release from intracellular stores, thus leads to myometrial contractions.
When given in appropriate doses during pregnancy, oxytocin is capable of eliciting rhythmic contractions in upper segment of uterus, similar in frequency, force and duration of spontaneous motor activity (similar to that observed during spontaneous labour).
Being synthetic, oxytocin in Oxytocin-Richter does not contain vasopressin, but even in its pure form oxytocin possesses some weak intrinsic vasopressin-like antidiuretic activity.
Based on in vitro studies, prolonged exposure of oxytocin had been reported to cause desensitisation of oxytocin receptors probably due to down-regulation of oxytocin-binding sites, destabilisation of oxytocin receptors mRNA and internalisation of oxytocin receptors.
Pharmacokinetics: With intravenous injection given at doses appropriate for induction or enhancement of labour, the uterine response sets in gradually and usually reaches a steady state within 20 to 40 minutes. Following intramuscular injection, the myotonic effect on the uterus appears in 3-7 minutes and persists for 2-3 hours.
The corresponding plasma levels of oxytocin are comparable to those measured during spontaneous first-stage labour. For example, oxytocin plasma levels in 10 pregnant women at term receiving 4 milliunits per minute intravenous infusion were 2 to 5 microunits/mL. Upon discontinuation of the infusion, or following a substantial reduction in the infusion rate, e.g. in the event of overstimulation, uterine activity declines rapidly but may continue at an adequate lower level.
The steady-state volume of distribution determined in 6 healthy men after intravenous injection is 12.2 L or 0.17 L/kg. Plasma protein binding is negligible for oxytocin. It crosses the placenta in both directions. Oxytocin may be found in small quantities in monther's breast milk.
Plasma half-life of oxytocin ranges from 3 to 20 minutes. Most of the drug is rapidly metabolised by the liver and the kidney. Oxytocin is inactivated by enzymatic hydrolysis, primarily by enzyme oxytocinase. Oxytocinase is a glycoprotein aminopeptidase that is produced during pregnancy and appears in the plasma. It is produced from both the mother and the foetus. The metabolites are excreted in urine whereas less than 1% of the oxytocin is excreted unchanged in urine. The metabolic clearance rate amounts to 20 mL/kg/min in the pregnant woman.
Renal impairment: No studies have been performed in renally impaired patients. However, considering the excretion of oxytocin and its reduced urinary excretion because of anti-diuretic properties, the possible accumulation of oxytocin can result in prolonged action.
Hepatic impairment: No studies have been performed in hepatically impaired patients. Pharmacokinetic alteration in patients with impaired hepatic function is unlikely, since metabolising enzyme, oxytocinase is not confined to liver alone and the oxytocinase levels in placenta during the term has significantly increased. Therefore, biotransformation of oxytocin in impaired hepatic function may not result in substantial changes in metabolic clearance of oxytocin.