Oxytocin is a 9-amino-acid peptide with an intrapeptide disulfide cross-link (Figure 37–5). Its amino acid sequence differs from that of vasopressin at positions 3 and 8.
B. Absorption, Metabolism, and Excretion
Oxytocin is administered intravenously for initiation and augmentation of labor. It also can be administered intramuscularly for control of postpartum bleeding. Oxytocin is not bound to plasma proteins and is rapidly eliminated by the kidneys and liver, with a circulating half-life of 5 minutes.
Oxytocin acts through G protein–coupled receptors and the phosphoinositide-calcium second-messenger system to contract uterine smooth muscle. Oxytocin also stimulates the release of
FIGURE 37–5 Posterior pituitary hormones and desmopressin. (Adapted, with permission, from Ganong WF: Review of Medical Physiology, 21st ed.
McGraw-Hill, 2003. Copyright © The McGraw-Hill Companies, Inc.) prostaglandins and leukotrienes that augment uterine contraction. In small doses oxytocin increases both the frequency and the force of uterine contractions. At higher doses, it produces sustained contraction.
Oxytocin also causes contraction of myoepithelial cells surrounding mammary alveoli, which leads to milk letdown. Without oxytocin-induced contraction, normal lactation cannot occur. At high concentrations, oxytocin has weak antidiuretic and pressor activity due to activation of vasopressin receptors.
Oxytocin is used to induce labor for conditions requiring expedited vaginal delivery such as uncontrolled maternal diabetes, worsening preeclampsia, intrauterine infection, or ruptured membranes after 34 gestational weeks. It is also used to augment protracted labor. Oxytocin can also be used in the immediate postpartum period to stop vaginal bleeding due to uterine atony.
Before delivery, oxytocin is usually administered intravenously via an infusion pump with appropriate fetal and maternal monitoring. For induction of labor, an initial infusion rate of 0.5–2 mU/min is increased every 30–60 minutes until a physiologic contraction pattern is established. The maximum infusion rate is 20 mU/min. For postpartum uterine bleeding, 10–40 units are added to 1 L of 5% dextrose, and the infusion rate is titrated to control uterine atony. Alternatively, 10 units of oxytocin can be administered by intramuscular injection.
During the antepartum period, oxytocin induces uterine contractions that transiently reduce placental blood flow to the fetus. The oxytocin challenge test measures the fetal heart rate response to a standardized oxytocin infusion and provides information about placental circulatory reserve. An abnormal response, seen as late decelerations in the fetal heart rate, indicates fetal hypoxia and may warrant immediate cesarean delivery.
When oxytocin is used judiciously, serious toxicity is rare. The toxicity that does occur is due either to excessive stimulation of uterine contractions or to inadvertent activation of vasopressin receptors. Excessive stimulation of uterine contractions before delivery can cause fetal distress, placental abruption, or uterine rupture. These complications can be detected early by means of standard fetal monitoring. High concentrations of oxytocin with activation of vasopressin receptors can cause excessive fluid retention, or water intoxication, leading to hyponatremia, heart failure, seizures, and death. Bolus injections of oxytocin can cause hypotension. To avoid hypotension, oxytocin is administered intravenously as dilute solutions at a controlled rate.