DINOPROST TROMETHAMINE, PROSTAGLANDIN F2aTROMETHAMINE
Chemistry - The tromethamine (THAM) salt of the naturally occurring prostaglandin F2alpha, dinoprost tromethamine occurs as a white to off-white, very hygroscopic, crystalline powder with amelting point of about 100°C. One gram is soluble in about 5 ml of water. 1.3 micrograms ofdinoprost tromethamine is equivalent to 1 micrograms of dinoprost. Dinoprost tromethamine mayalso be known as dinoprost trometamol, PGF2alpha THAM, or prostaglandin F2alphatromethamine.
Unlabeled uses of dinoprost include its use in small animals as an abortifacient agent and as adjunctive medical therapy in pyometra. Although not approved, dinoprost is used also in sheep and goat reproductive medicine.
Contraindications/Precautions - Unless being used as an abortifacient or parturition inducer, dinoprost should not be used during pregnancy in all species. Dinoprost is contraindicated inanimals with bronchoconstrictive respiratory disease (e.g., asthma, "heavey" horses). It should notbe administered intravenously.
In swine, dinoprost should not be administered prior to 3 days of normal predicted farrowing asincreased neonatal mortality may result.
According to the manufacturer, dinoprost is contraindicated in mares with acute or subacutedisorders of the vascular system, GI tract, respiratory system or reproductive tract.
Dinoprost should be used with extreme caution, if at all, in dogs or cats greater than 8 years old, orwith preexisting cardiopulmonary or other serious disease (liver, kidney, etc.). Some cliniciansregard closed-cervix pyometra as a relative contraindication to the use of dinoprost.
In mares, transient decreased body (rectal) temperature and sweating have been reported mostoften. Less frequently, increased respiratory and heart rates, ataxia, abdominal pain and lying downhave also been noted. These effects are generally seen within 15 minutes of administration andresolve within an hour.
In swine, dinoprost has caused erythema and pruritis, urination, defecation, slight ataxia, hyperpnea, dyspnea, nesting behavior, abdominal muscle spasms, tail movements, increased vocalization and salivation. These effects may last up to 3 hours. At doses of 10 times recommended, vomiting may be seen in swine.
In dogs and cats, dinoprost can cause abdominal pain, emesis, defecation, urination, pupillary dilation followed by constriction, tachycardias, restlessness and anxiety, fever, hypersalivation, dyspnea and panting. Cats may also exhibit increased vocalization and intense grooming behavior.
Severity of effects is generally dose dependent. Defecation can be seen even with very low dosages.
Reactions generally appear in 5-120 minutes after administration and may persist for 20-30minutes. Fatalities have occurred (especially in dogs) after use. Dogs and cats should be monitoredfor cardiorespiratory effects, especially after receiving higher dosages.
When used as an abortifacient in humans, dinoprost causes nausea, vomiting or diarrhea in about50% of patients.
Overdosage - Dogs are apparently more sensitive to the toxic effects of dinoprost than otherspecies. The LD50 in the bitch has been reported to be 5.13 mg/kg after SQ injection which may beonly 5X greater than the recommended dose by some clinicians.
In cat le, swine, and horses, dinoprost's effects when administered in overdose quantities areoutlined above in the Adverse effects section. If symptoms are severe in any species and requiretreatment; supportive therapy is recommended.
Storage, Stability, Compatibility
Dinoprost for injection should be stored at room temperature(15-30°C) in airtight containers. The human-approved product is recommended to be stored underrefrigeration. Dinoprost is considered to be relatively insensitive to heat, light, and alkalis.Pharmacology - DINOPROST TROMETHAMINE, PROSTAGLANDIN F2aTROMETHAMINE
Prostaglandin F2alpha has several pharmacologic effects on the female reproductive system, including stimulation of myometrial activity, relaxation of the cervix, inhibition of steroidogenesis by corpora lutea, and can potentially lyse corpora lutea.Uses, Indications - Lutalyse® (Upjohn) is labeled for use in cat le as a luteolytic agent for estrous synchronization, unobserved (silent) estrous in lactating dairy cattle, pyometra, and as an abortifacient in feedlot and non-lactating dairy cattle. It is labeled in swine to act as a parturitient inducing agent. The product is labeled for use in mares as a luteolytic agent to control the time of estrus in cycling mares and to assist in inducing estrus in "difficult to breed mares."Unlabeled uses of dinoprost include its use in small animals as an abortifacient agent and as adjunctive medical therapy in pyometra. Although not approved, dinoprost is used also in sheep and goat reproductive medicine.
Pharmacokinetics - DINOPROST TROMETHAMINE, PROSTAGLANDIN F2aTROMETHAMINE
In studies done in rodents, dinoprost was demonstrated to distribute veryrapidly to tissues after injection. In cattle, the serum half-life of dinoprost has been stated to be only"minutes" long.Contraindications/Precautions - Unless being used as an abortifacient or parturition inducer, dinoprost should not be used during pregnancy in all species. Dinoprost is contraindicated inanimals with bronchoconstrictive respiratory disease (e.g., asthma, "heavey" horses). It should notbe administered intravenously.
In swine, dinoprost should not be administered prior to 3 days of normal predicted farrowing asincreased neonatal mortality may result.
According to the manufacturer, dinoprost is contraindicated in mares with acute or subacutedisorders of the vascular system, GI tract, respiratory system or reproductive tract.
Dinoprost should be used with extreme caution, if at all, in dogs or cats greater than 8 years old, orwith preexisting cardiopulmonary or other serious disease (liver, kidney, etc.). Some cliniciansregard closed-cervix pyometra as a relative contraindication to the use of dinoprost.
Adverse Effects, Warnings
In cattle, increased temperature has been reported when administeredin overdose (5-10X recommended doses) quantities. Limited salivation and bacterial infections atthe injection site have been reported. If administered intravenously, increased heart rates have beennoted.In mares, transient decreased body (rectal) temperature and sweating have been reported mostoften. Less frequently, increased respiratory and heart rates, ataxia, abdominal pain and lying downhave also been noted. These effects are generally seen within 15 minutes of administration andresolve within an hour.
In swine, dinoprost has caused erythema and pruritis, urination, defecation, slight ataxia, hyperpnea, dyspnea, nesting behavior, abdominal muscle spasms, tail movements, increased vocalization and salivation. These effects may last up to 3 hours. At doses of 10 times recommended, vomiting may be seen in swine.
In dogs and cats, dinoprost can cause abdominal pain, emesis, defecation, urination, pupillary dilation followed by constriction, tachycardias, restlessness and anxiety, fever, hypersalivation, dyspnea and panting. Cats may also exhibit increased vocalization and intense grooming behavior.
Severity of effects is generally dose dependent. Defecation can be seen even with very low dosages.
Reactions generally appear in 5-120 minutes after administration and may persist for 20-30minutes. Fatalities have occurred (especially in dogs) after use. Dogs and cats should be monitoredfor cardiorespiratory effects, especially after receiving higher dosages.
When used as an abortifacient in humans, dinoprost causes nausea, vomiting or diarrhea in about50% of patients.
Overdosage - Dogs are apparently more sensitive to the toxic effects of dinoprost than otherspecies. The LD50 in the bitch has been reported to be 5.13 mg/kg after SQ injection which may beonly 5X greater than the recommended dose by some clinicians.
In cat le, swine, and horses, dinoprost's effects when administered in overdose quantities areoutlined above in the Adverse effects section. If symptoms are severe in any species and requiretreatment; supportive therapy is recommended.