Volume 44 | Issue 2 Article 5 1982 Clinical Applications of Prostaglandins in Dogs and Cats Edward C. Briles Iowa State University Lawrence E. Evans Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/iowastate_veterinarian Part of the Lipids Commons, and the Small or Companion Animal Medicine Commons Recommended Citation Briles, Edward C. and Evans, Lawrence E. (1982) "Clinical Applications of Prostaglandins in Dogs and Cats," Iowa State University Veterinarian: Vol. 44 : Iss. 2 , Article 5. Available at: https://lib.dr.iastate.edu/iowastate_veterinarian/vol44/iss2/5 This Article is brought to you for free and open access by the Journals at Iowa State University Digital Repository. It has been accepted for inclusion in Iowa State University Veterinarian by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Clinical Applications of Prostaglandins in Dogs and Cats by Edward C. Briles, DVM* Lawrence E. Evans, DVM, PhD** In the biological sciences today there are few previously been shown to make smooth muscle 3 4 substances that generate as much interest as contract. • It wasn't until 1957 that two pro­ prostaglandins. They have found widespread staglandins (PGE l, PGF la) were isolated in use in veterinary medicine, yet are only ap­ pure crystalline form and soon more pro­ proved by the FDA for specific uses in cattle staglandins were characterized, all of which and horses. However, practical applications in were found to be 20-carbon unsaturated car­ the dog and cat have been reported by clini­ boxylic acids with a cyclopentane ring. cians and have been evaluated in clinical Thereafter, it was found that all prostaglan­ research projects. dins are derived from linoleic and arachidonic The purpose ofthis paper is, first, to provide fatty acids; arachidonate is in the phospho­ an overview of these areas where prostaglan­ lipids of cell membranes of all mammalian dins may be utilized in canine and feline prac­ tissues. 5 tice. Secondly, owing to the fact of its recent There are several main classes of pro­ emergence on the veterinary medical scene, a staglandins: E,F,I,A,B,C,D, distinguished by briefbackground on prostaglandins will be in­ the constituents of the cyclopentane ring. The eluded to facilitate understanding. main classes are further subdivided in accord with the number of double bonds in the side BACKGROUND chains. 3 The most biologically active com­ Prostaglandins are naturally occurring pounds are PGE2, PGF2a , TXA, and PGI2 all substances classified as autocoids, from the of wh~ch have a pair of double bonds and are, Greek autos ("self') and akos ("medicinal therefore, designated as the 2 series. 5 The E agent"), and referred to as parahormones, and Fa Groups are the most abundant in humoral mediators, or local hormones because reproductive tissues, especially PGE2 and they are not systemically circulating hor­ PGF2a , with only prostaglandin F2a and its mones, but act only on the local level. They are analogues available commercially for produced by most biological tissues and are veterinary use in this country. PGF2a is prob­ detectable in most body fluids. Members ofthe ably the natural uterine luteolytic factor in prostaglandin family have specific reproduc­ most species. tive functions and also participate as mes­ The first product on the market was the senger-type agents in the function of nearly THAM salt of PGF2a , dinoprost trometha­ every physiologic system in the body.l Their mine (Prostin F2alphaR -Upjohn Co.). It is actions are believed to be mediated by cyclic labelled for use only in horses to control the AMP and cyclic G MP.2 time of estrus in cyling mares and to treat In 1936, Von Euler derived the name "pro­ mares with prolonged diestrual periods. The staglandin" from the prostate gland to identify approved dosage is 1 mg/l00 lbs. (0.022 a lipid-soluble acid that he had found to be the mg/kg) administered as a single intramuscular active substance in human semen which had injection. The Upjohn Co. subsequently came out with another dinoprost product R *Dr. Briles is a 1982 graduate of the College of (Lutalyse ) which is identical to Prostin Veterinary Medicine at Iowa State University. ** Dr. Evans is a professor in Veterinary Clinical F2alpha except it is labelled for synchroniza­ Sciences at Iowa State University. tion of estrus among beef cattle and nonlac- 90 Iowa State Veterinarian tating dairy heifers, and for abortion offeedlot plete luteolysis was induced and abortion oc­ heifers before 100 days of gestation. The ap­ curred when plasma progesterone was proved dosage is 25 mg as a total dose ad­ depressed to 0.6-1.4 ng/ml from pretreatment ministered intramuscularly. Another com­ levels of 3-40 ng/nll. 11 mercial product is prostalene (Synchro­ It has been the authors' experience that the ceptR-Diamond) which is a PGF2a analogue proper length of treatment (six injections, one labelled for use only in horses at a dosage of 5 every 12 hours) must be maintained to pro­ ug/kg. duce a successful abortion. In an earlier study Besides the approved uses, PGF 2a is used in luteolysis and abortion were not produced the bovine therapeutically for unobserved when a larger total dose (250 ug/kg) was given estrus, pyometra, mummified fetus, luteinized intraveneously within a seven hour period. 14 6 cysts, and induction of parturition. Other It also seems imperative that the treatment unapproved uses have also been recognized in 7 be delayed until the mid to late gestation the equine. ,8 PGF has been used for induc­ 2a period since the early corpora lutea in the bitch tion of parturition in swine. 9 are more refractory to PGF2a' Similarly, in Women of child-bearing age, asthmatics, cattle doses of PGF 2a must be given after day and persons with bronchial and other five of the estrous cycle in order to get respiratory problems should be very careful luteolysis. 15 An hypothesis has been when handling this drug because prostaglan­ proposed16 and supported17 that explains the dins of the F series are effective abortifacients resistance of the newly formed corpus luteum and potent bronchoconstrictors in human by the fact that "the preovulatory surge of LH beings. saturates the regulatory units ofthe luteal cells Uses ofprostaglandin reported in this paper and that it is this bound hormone which are of the dinoprost tromethamine product protects the young corpus luteum." Previous­ and are in nonapproved species based solely ly, corpus luteum receptors for PGF2a were on results of experimental use. The FDA does identified. 18 not sanction such uses, therefore, the It is not surprising that this regimen of ex­ veterinarian assumes full responsibility. ogenously administered PGF2a (every 12 hours for three days) is effective in producing ABORTION luteolysis in the bitch when considering the en­ It has been established that endogenous dogenous PGF2a release patterns associated PGF of uterine origin in the cow is in­ with luteolysis in other species. Parallels tend 2a to appear between the natural release of strun1.ental in terminating luteal function in PGF and the above-mentioned regimen in the nonpregnant animal thus returning it to 2a dogs. In the bovine the production and release heat. PGF 2a release from the uterus is also im­ ofPCF 2a by the uterus is known to be pulsatile portant for the prepartum lysis of the corpus and precise. During the estrous cycle PGF2a is luteum which removes the progesterone block released for two to three days as rapid pulses and for increasing the contractile strength of with a duration of one to five hours prior to the uterine musculature prior to parturition. 10 and during luteolysis, which is indicated by Consequently, exogenous PGF2a has proven decreasing levels of plasma progesterone. 19 to be an effective abortifacient in cows. In dogs and cats it is known that prostaglandins play The exact mechanism for PGF2a induced an important role in reproductive function but luteolysis has not been worked out in any that role is not nearly as well worked out as it species but some theories are as follows: an­ is in the bovine. tagonism with LH or prolactin; promotion of PGF2a can be used to terminate gestation in fragility in lysosomes; contractile effect on the ll 12 13 the bitch . and queen. One study has utero-ovarian vein, resulting in reduced blood flow through the ovary; decreased stores ofthe reported that PGF2a given intramuscularly to pregnant beagle bitches from day 33 to day 53 progesterone precursors, cholesterol esters; or of gestation at a dosage of either 20 ug/kg decreased esterase activity. every 8 hours or 30 ug/kg every 12 hours for 72 PCF2a also induces strong myometrial con­ hours (180 ug/kg total dose) will cause the tractions in the bitch which plays a role in the fetuses to abort within 56 to 80 hours after induced abortion along with at least a de­ treatment begins. ll It was shown that com- creased luteal function. Vol. 44) No. 2 91 It has also been reported that a one-shot that 80% of injected PGF2a is excreted in the dosage of 1 mg/kg PGF2a in the bitch is an urine within six hours in the bovine. 4 A mild effective abortifacient. 12 However, details con­ drop in body temperature (i-2°F) similar to cerning the application of this dosage are not that preceding normal parturition may be available. noted. 11 After the second or third injection the The veterinarian is often faced with the bitch may display vigorous nest building client who believes his bitch may have been behavior. Fetal expulsions should be expected bred to an undesirable male dog.