OXYTOCIN
Chemistry - A nonapeptide hypothalamic hormone stored in the posterior pituitary (in mammals), oxytocin occurs as a white powder that is soluble in water. The commercially available preparationsare highly purified and have virtually no antidiuretic or vasopressor activity when administered atusual doses. Oxytocin potency is standardized according to its vasopressor activity in chickens andis expressed in USP Posterior Pituitary Units. One unit is equivalent of approximately 2.0 - 2.2micrograms of pure hormone.
Commercial preparations of oxytocin injection have their pH adjusted with acetic acid to 2.5-4.5and multi-dose vials generally contain chlorbutanol 0.5% as a preservative.
Oxytocin is reportedly compatible with most commonly used intravenous fluids and the following drugs: chloramphenicol sodium succinate, metaraminol bitartrate, netilmicin sulfate, sodiumbicarbonate, tetracycline HCl, thiopental sodium and verapamil HCl.
Oxytocin is reportedly incompatible with the following drugs: fibrinolysin, norepinephrinebitartrate, prochlorperazine edisylate and warfarin sodium. Compatibility is dependent upon factorssuch as pH, concentration, temperature and diluents used. It is suggested to consult specializedreferences for more specific information (e.g., Handbook on Injectable Drugs by Trissel; seebibliography).
Oxytocin can facilitate milk ejection, but does not have any galactopoietic properties. Whileoxytocin only has minimal antidiuretic properties, water intoxication can occur if it is administeredat too rapid a rate and/or if excessively large volumes of electrolyte-free intravenous fluids areadministered.
Uses, Indications - In veterinary medicine, oxytocin has been used for induction or enhancementof uterine contractions at parturition, treatment of postpartum retained placenta and metritis, uterineinvolution after manual correction of prolapsed uterus in dogs, and in treating agalactia.
While oxytocin can be administered intranasally, absorption can be erratic. Oxytocin is distributedthroughout the extracellular fluid. It is believed that small quantities of the drug cross the placentaand enter the fetal circulation.
In humans, the plasma half-life of oxytocin is about 3-5 minutes. In goats, this value has beenreported to be about 22 minutes. Oxytocin is metabolized rapidly in the liver and kidneys and acirculating enzyme, oxytocinase can also destroy the hormone. Very small amounts of oxytocin areexcreted in the urine unchanged.
Contraindications/Precautions - Oxytocin is considered to be contraindicated in animals withdystocia due to abnormal presentation of fetus(es), unless correction is made. When usedprepartum, oxytocin should be used only when the cervix is relaxed naturally or by the prioradministration of estrogens (Note: Most clinicians avoid the use of estrogens, as natural relaxationis a better indicator for the proper time to induce contractions).
In humans, oxytocin is considered to be contraindicated in patients with significant cephalopelvicdisproportion, unfavorable fetal positions, in obstetrical emergencies when surgical intervention iswarranted, severe toxemia or when vaginal delivery is contraindicated. Oxytocin is alsocontraindicated in patients who are hypersensitive to it. Nasally administered oxytocin iscontraindicated in pregnancy.
Before using oxytocin, treat hypoglycemia or hypocalcemia if present.
Overdosage - Effects of overdosage on the uterus depend on the stage of the uterus and the position of the fetus(es). Hypertonic or tetanic contractions can occur leading to tumultuous labor, uterine rupture, fetal injury or death.
Water intoxication can occur if large doses are infused for a long period of time, especially if largevolumes of electrolyte-free intravenous fluids are concomitantly being administered. Earlysymptoms can include listlessness or depression. More severe intoxication symptoms can includecoma, seizures and eventually death. Treatment for mild water intoxication is stopping oxytocintherapy and restricting water access until resolved. Severe intoxication may require the use ofosmotic diuretics (mannitol, urea, dextrose) with or without furosemide.
Commercial preparations of oxytocin injection have their pH adjusted with acetic acid to 2.5-4.5and multi-dose vials generally contain chlorbutanol 0.5% as a preservative.
Storage, Stability, Compatibility
Oxytocin injection should be stored at temperatures of lessthan 25°C, but should not be frozen. Some manufacturers recommend storing the product underrefrigeration (2-8°C), but some products have been demonstrated to be stable for up to 5 years ifstored at less than 26°C.Oxytocin is reportedly compatible with most commonly used intravenous fluids and the following drugs: chloramphenicol sodium succinate, metaraminol bitartrate, netilmicin sulfate, sodiumbicarbonate, tetracycline HCl, thiopental sodium and verapamil HCl.
Oxytocin is reportedly incompatible with the following drugs: fibrinolysin, norepinephrinebitartrate, prochlorperazine edisylate and warfarin sodium. Compatibility is dependent upon factorssuch as pH, concentration, temperature and diluents used. It is suggested to consult specializedreferences for more specific information (e.g., Handbook on Injectable Drugs by Trissel; seebibliography).
Pharmacology - OXYTOCIN
By increasing the sodium permeability of uterine myofibrils, oxytocin stimulatesuterine contraction. The threshold for oxytocin-induced uterine contraction is reduced withpregnancy duration, in the presence of high estrogen levels and in patients already in labor.Oxytocin can facilitate milk ejection, but does not have any galactopoietic properties. Whileoxytocin only has minimal antidiuretic properties, water intoxication can occur if it is administeredat too rapid a rate and/or if excessively large volumes of electrolyte-free intravenous fluids areadministered.
Uses, Indications - In veterinary medicine, oxytocin has been used for induction or enhancementof uterine contractions at parturition, treatment of postpartum retained placenta and metritis, uterineinvolution after manual correction of prolapsed uterus in dogs, and in treating agalactia.
Pharmacokinetics - OXYTOCIN
Oxytocin is destroyed in the GI tract and, therefore, must be administeredparenterally. After IV administration, uterine response occurs almost immediately. Following IMadministration, the uterus responds generally within 3-5 minutes. The duration of effect in dogsafter IV or IM/SQ administration has been reported to be 13 minutes and 20 minutes, respectively.While oxytocin can be administered intranasally, absorption can be erratic. Oxytocin is distributedthroughout the extracellular fluid. It is believed that small quantities of the drug cross the placentaand enter the fetal circulation.
In humans, the plasma half-life of oxytocin is about 3-5 minutes. In goats, this value has beenreported to be about 22 minutes. Oxytocin is metabolized rapidly in the liver and kidneys and acirculating enzyme, oxytocinase can also destroy the hormone. Very small amounts of oxytocin areexcreted in the urine unchanged.
Contraindications/Precautions - Oxytocin is considered to be contraindicated in animals withdystocia due to abnormal presentation of fetus(es), unless correction is made. When usedprepartum, oxytocin should be used only when the cervix is relaxed naturally or by the prioradministration of estrogens (Note: Most clinicians avoid the use of estrogens, as natural relaxationis a better indicator for the proper time to induce contractions).
In humans, oxytocin is considered to be contraindicated in patients with significant cephalopelvicdisproportion, unfavorable fetal positions, in obstetrical emergencies when surgical intervention iswarranted, severe toxemia or when vaginal delivery is contraindicated. Oxytocin is alsocontraindicated in patients who are hypersensitive to it. Nasally administered oxytocin iscontraindicated in pregnancy.
Before using oxytocin, treat hypoglycemia or hypocalcemia if present.
Adverse Effects, Warnings
When used appropriately at reasonable dosages, oxytocin rarelycauses significant adverse reactions. Most adverse effects are as a result of using the drug in inappropriate individuals (adequate physical exam and monitoring of patient are essential) or at toohigh doses (see Overdosage below). Hypersensitivity reactions are a possibility in non-syntheticallyproduced products. Repeated bolus injections of oxytocin may cause uterine cramping anddiscomfort.Overdosage - Effects of overdosage on the uterus depend on the stage of the uterus and the position of the fetus(es). Hypertonic or tetanic contractions can occur leading to tumultuous labor, uterine rupture, fetal injury or death.
Water intoxication can occur if large doses are infused for a long period of time, especially if largevolumes of electrolyte-free intravenous fluids are concomitantly being administered. Earlysymptoms can include listlessness or depression. More severe intoxication symptoms can includecoma, seizures and eventually death. Treatment for mild water intoxication is stopping oxytocintherapy and restricting water access until resolved. Severe intoxication may require the use ofosmotic diuretics (mannitol, urea, dextrose) with or without furosemide.