Rabu, 17 Disember 2008


Description: Endogenous oxytocin is a hormone secreted by the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior pituitary. Oxytocin is infused intravenously to induce labor and to stimulate uterine contractions after labor has begun. Intranasal oxytocin is used to promote the initial ejection of milk postpartum, once milk has formed. Oxytocin was approved by the FDA in 1962.
Mechanism of Action: Synthetically prepared oxytocin elicits all of the pharmacological reactions produced by the endogenous hormone. The response of the uterus to oxytocin is dependent on the stage of pregnancy. The response of the uterus to oxytocin increases as the third trimester progresses. In the early stages of pregnancy, oxytocin produces uterine contractions only if a very high dose is used. Oxytocin is most effective at or close to term. Oxytocin selectively stimulates the smooth muscle cells of the uterus by enhancing the sodium permeability of the myofibril membranes. Rhythmic contractions of the uterus are produced. Oxytocin also increases the frequency and force of existing contractions.
Estrogen levels play a role in the uterine response to oxytocin; high concentrations increase the response. This increase in oxytocin receptors is most pronounced toward the end of pregnancy, during labor, and following delivery. Oxytocin-induced increases in the amplitude and frequency of uterine contractions reduce cervical tone, producing dilation of the cervix and a brief impediment to uterine blood flow. Oxytocin also causes contraction of the myoepithelial cells surrounding the alveolar ducts of the breast, stimulating milk ejection. Milk is forced from the alveolar channels into the large sinuses, from where it is readily available. If oxytocin is absent, the milk-ejection reflex in the breasts fails.
Large doses of oxytocin decrease both systolic and diastolic blood pressure through a transient relaxation of vascular smooth muscle. Any oxytocin-induced decrease in blood pressure is followed by a mild but sustained increase. Obstetrical doses of oxytocin alone generally are not large enough to produce noticeable changes in blood pressure. Arterial pressure can drop sharply in anesthetized patients. Oxytocin has little antidiuretic effect, but large doses can produce water intoxication when used concurrently with large volumes of intravenous fluids.
Pharmacokinetics: Oxytocin is metabolized by chymotrypsin in the GI tract and therefore is not administered orally. Administration by any parenteral route is effective. The uterine response to oxytocin administration is almost instantaneous following IV injection and occurs within 3-5 minutes following IM injection. Following intranasal use, contractions of the myoepithelial tissue surrounding the alveoli of the breasts begin within minutes and persist for about 20 minutes. Plasma half-life is between 1 and 6 minutes. Uterine response subsides within 1 hour following IV administration and within 2-3 hours following IM administration. The drug distributes throughout the extracellular fluid, with minimal amounts reaching the fetus.
The amount of an enzyme, oxytocinase, in plasma capable of degrading oxytocin increases dramatically during pregnancy. This enzyme may originate from the placenta and regulate the amount of oxytocin in the uterus. It appears to have little effect on plasma levels of oxytocin because plasma half-life is the same for males and females. Oxytocin is rapidly removed from plasma by the liver and the kidneys, with only small amounts being excreted unchanged in the urine.

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