Journal of Canine Development & Research 2020 & "ee ISSN - 0973-3272 Vol (16) 13-18 Journal of Canine Development & Research website: www:jedrindia.com REVIEW ARTICLE MEDICAL MANAGEMENT OF CANINE PYOMETRA Sasi’ and "GN. Purohit’ Department of Veterinary Gynecology and Obstetrics College of Veterinary and Animal Science, Bikaner Rajasthan University of Veterinary and Animal Sciences Bikaner-334001, Rajasthan, India 'MYSe.Scholar Corresponding author email: gnpobs@ gmail.com *Professor Mobile:9414325045 ARTICLE HISTORY ABSTRACT Received; 21,062021 Medical therapy of canine pyometra is suggested in young Revised: 20072001 bitches, bitches in poor condition, bitches that are poor surgical Accepted —: 23082021 risks and to improve the general status of the bitch prior to surgery. The drugs used for medical therapy include Rey words : prostaglandins, oxytocin and ergot derivatives, anti-prolactins, Bitch anti-progestins and drugs in combination. The potential benefits sanine and limitations of each of these drugs are discussed in this mini- -yometra view Prostaglandins revie Aslepristone Mifepristone yyometra or chronic purulent endometritis is a common, metestrual discase mainly affecting bitches over 8 years of age (Chaistain eral, 1999; Egenvall etal,, 2001). Alarge proportion (31.7%) of aged bitches presented to the clinics is affected with pyometra (Nagar et al, 2008), The disease generally occurs following estrus and generally during the luteal phase (Blendinger et al, 1997), Canine pyometra is a common reproductive syndrome of intact, sexually mature bitches during met/diestrus stage with various clinical as well as pathological signs specific to reproductive system along with systemic signs (Franson, 2003). Itcan be classified as open cervix or close cervix pyometra, Closed cervix pyometrais particularly dangerous, so it needs early recognition (Baithalu ef al,, 2010). An important clinical sign is malodorous, sanguineous or mucopurulent vaginal discharge with general symptoms such as vomiting, polyuria, polydipsia, depression, anorexia and occasionally fever (Qureshi et al, 2002; Nagar etal, 2008). Till date, ultrasonography is the best diagnostic method (Qureshi et al, 2008) while radiology and serological test are also helpful. BJournal of Canine Development & Research 2020 Recently, the estimation of inflammatory mediators (acute phase proteins and prostaglandin ‘metabolites) has appeared as marker for diagnosis of the pyometra, Determination of levels of inflammatory mediators has emerged as an important diagnostic method because it can be helpful in prognosis of the condition. Surgical removal of the ovaries and uterus (ovariohysterectomy) is considered the safest and ‘most eflective treatment, as the source of infection is removed and recurrence prevented (Hagman, 2018); however, medical therapy can be considered in less severe cases and younger bitches intended toretain their breeding potential (Hagman, 2018). In this review the possible medical therapies of canine pyometra are discussed. Indications for medical treatment ‘Medical therapy isnotindicated ifthe affected bitch has severe hepato-renal involvement (Hagman, 2018). If condition is not life threatening and the animal is particularly valuable, in such cases, restoration of fertility may be attempted with medical agents (Hagman, 2018; Fieni er al, 2014), The following may be the few candidates for consideration of medical therapy 1 Young breeding bitches, Bitches in very poor condition or old bitches, Normothermic bitches, in whom anaesthesia ‘would be dangerous, Cases where the owners want to keep costs at a minimum. ‘To improve the general status of the bitch prior to surgery, Principles of medical treatment Induction of luteolysis or prevention of progesterone binding to its receptors for prevention of progesterone effects is the usual principle of therapy (Hagman, 2018), Now-a- days PGF2alpha used either alone or in ‘combination with other drugs like prolactin inhibitor or progesterone receptor blocker for this effect Baithalu eral, 2010). Expulsion of the uterine contents by allowing cervical relaxation in closed pyometra either by the use of prostaglandins or progesterone receptor blockers. Use of broad- spectrum antibiotics for inhibition of bacterial growth should be concomitant to other therapies (Nagar er al., 2008). Facilitating uterine regeneration by prolonging anestrus has been mentioned (Baithalu et al, 2010). ‘Medical treatment Prostaglandin drugs Oxytocin and ergot derivatives Anti-prolactin drugs Anti progestin drugs Drugsin combination Prostaglandins PGF? alpha treatments a practical treatment for pyometra when reproduction is desired. PGF2 alpha brings lysis of CL, cervical relaxation which permits drainage of exudate and promotes myometrial contraction. These actions are dependent on the dosage, route and frequency of administration. PG therapy has potential side effects in dog, including vomition, diarrhea, increased salivation so clients consent must be taken before itsuse. PGF2alpha should be used with caution in case of closed cervix pyometra because of the chance of uterine rupture (Baithalu et al,, 2010), Prostaglandin-based drugs which have been tested in the canine and for which safe dosages have been developed include natural PGF2a (Dinoprost), Synthetic cloprostenol and alfaprostol (20 meg/ kg bwt /bid/od). A less frequently used prostaglandin is carboprost tromethamine (Nagar et al., 2008). PG has both luteolytic and uterotonic properties which were utilized for the treatment of pyometta, ‘Therapeutic protocol includes intramuscular injection of 100-250 jig/kg bwt of natural or 10 g/kg bwt of synthetic PG for 5-7 days, “4Journal of Canine Development & Research 2020 Prostaglandin (PGF2a) at the dose rate of 150- 200 igikg bwt sc /day for more than 10 days showed 100% results (Myhre, 2016), which may be due the fact that PGF2c causes luteolysis, which leads to progesterone block removal (Renton er al, 1993). Comparison of the uterotonic effect of two different doses administered via intramuscular injection (250. ig /kg vs 50 ig /kg bw), in bitches in diestrus, demonstrated that uterine contractions were equivalent. The highest dose was effective for 32 3 min and the lowest, for 23 3 min, (Burke, 1982; Nelson et al., 1982; Schille, 1986). Uterine rupture is a very rare event, and can be caused by any drug stimulating uterine contractility. Based on studies done in diestrus bitches by Wheaton and Barbee (1993), PGF2a. doses of ‘50 and 250 meg/kg bwt cause a maximum uterine pressure of 476 and 519 mm Hg, respectively (no significant difference), and a duration of the uterine contraction significantly lower at 23::3 minutes for the lower dosage vs 303 minutes for the higher dosage (the contraction is about 7 ‘minutes longer with the higher dose), respectively. Efficacy of low doses of natural PGF2cthas been reported for bitches with pyometra (Lange etal, 1997). Also, intravaginal infusion of PG at 0.15 mg/kg, bwt (0.30 mL/10 kg bwt) has been found successful in 86.6% cases (Fransson and Ragle, 2003), Immediately after infusion, the hindquarters, of the animal were raised for 3 to 5 minutes to prevent loss ofthe infused substance. Recurrence was not noted within the 12 months following treatment (Gabor er al., 1999). No side-effect has been found through this protocol and hence generates new therapeutic possibilities. However, further trials for validation are recommended (Verstegen et al., 2008; Jackson, 1979) Side-effects are associated with the use of natural PG include panting, salvation, vomiting, training, diarthoea, pyrexia (Contri et al, 2014) and risk of uterine rupture in closed-cervix pyometra (Hubler etal, 1991). These can be prevented by administration of atropine 15 min prior to PG injection, use of synthetic PG or progressive administration of PG dosage. Earlier study has reported the injection of 0.10 mg/kg bwt on Day 1,0.20 mg/kg bwt on Day 2 and then 0.25 mg/kg bwt to check the side- effects (Feldman and Nelson, 2004). Oxytocin and ergot derivatives ‘When the cervix is open the uterus can be easily emptied stimulating contractility of the myometrium Oxytocin and ergot derivatives induce very strong, short-lasting contraction of the uterine wall which ‘may be dangerousif the uterusis fully dilated with pus and/or the uterine wall is thin and atrophied or the cervix is only partially dilated, as this may cause either a) the pus to be forced backward into the uterine tubes and then into the abdomen, orb) the uterine wall to rupture (Fieni etal, 2014) Based on studies done in diestrous bitches by Wheaton and Barbee (1993), oxytocin dose of 5 ig /kg bw iv will cause a maximum uterine pressure of 6028 mm Hg lasting for only 14:2 minutes. However, under most clinical situations oxytocin ‘administration has litle value. Anti-prolactin drugs Prolactin is luteotropic in bitch hence use of anti- prolactin drags results in rapid reduction in the level of blood progesterone (Antonov et al, 2015). Anti-prolactin drugs such as Bromocriptine and Cabergoline are substantially used for the treatment of pyometra (Hagman, 2018), Bromocriptine at 20 g/kg bwt or Cabergoline at Syg/kg bwt can be used either alone or in combination with PG Antiprogestins Use of progesterone blockers such as mifepristone (Hoffman and Schuler, 2000; Nagar et al., 2008) or aglepristone (Wehrend and Traschbostedt, 2003; Amold er al., 2015) has proved better 158Journal of Canine Development & Research 2020 protocol of choice, Further Contri ef al, (2015) successfully used a protocol in which aglepristone ‘combined with a short duration (6 days) antibiotic cover proved efficacious. Nagar et al, 2008 found mifepristone administered orally at the dose rate of 100-200 mg for 2-3 days effective in therapy of pyometra in bitches. Progesterone receptor blocker like aglepristone competitively prevents progesterone from binding to its receptor. There is controversy of its use, to induce uterine contractions if used alone, The combination of aglepristone with cloprostenol is consideted more effective in medical treatment of ‘open and closed cervix pyometra than aglepristone alone. Aglepristone at 10 mg/kg bwt sc on day 1, 2 and 8 or on Day 15 has been reported to be effective in both open and closed- cervix pyometra, if uterine lumen is still visible on ultrasonographic examination Fieni eral, 2014). Previous report indicated 100% effectiveness, 95.7% and 100% ‘complete evacuation of uterine content within 14 and 21 days post-treatment, respectively. A previous study also reported that the drug can solely be responsible for evacuation ofthe uterine contents (Okano ef al., 1998). It has been assumed that aglepristone blocks the progesterone receptors and increases the myometrial contractibility. The myometrial contractibility ‘occurs due to the secretion of endogenous PG as 2 consequence of inflammation (Gunay et al, 2011) ‘Treatment with the antiprogestin RU 46534 in bitches with pyometra has been associated with clinical recovery and successful post treatment breedingresulted in two of six dogs in apreliminary clinical study (Breitkopf et al., 1997). Antiprogestin promotes expulsion of uterine contents by myometrial contraction in cases in which the pre-treatment plasma progesterone ‘concentrations are higher than 2 mg/m, The bitches in the preliminary study were followed up only to the next estrous cycle, and the recovery rate was not evaluated (Breitkopf etal, 1997). Drugsin combination, ‘The drugs or hormones in combination can be used to increase the efficacy of the treatment, Two subcutaneous injections of aglepristone at 10 mg/ kg 24 h apart followed by a second injection 8 days later or third injection after 15 days if required can be given on combination with PG at 1 g/kg, ‘bwtfrom:3 to 7 days of treatment. The combination increases the success rate from 60% (when aglepristone was used alone) to 84% on day 90. post-treatment (Fieni et al,, 2014). Similarly, combination of antiprolactin and PG is known to have synergistic action on luteolysis (Gabor etal, 1999; Onclin and Verstegen, 1996). Cabergoline administered orally daily at 5 ugikg ‘bwtfor7 days can be combined with PG injections. The protocol resulted in decreased serum progesterone and cervical relaxation within 24-48 has compared to single PG treatment. Another protocol with combination of cabergoline (@ 5 Pglkg bwt po od) and cloprostenol (@ 1 Pg/kg bwt od) for seven days was found useful. A recent protocol used for the treatment of pyometra is administration of third generation GnRH antagonist acyline @ 330 g/kg bwtorally (ingle dose) with amoxicillin-clavulanate @ 12.5 mg/kg bwt bid, orally for seven days provided promising results (Batista etal, 2016). Itis important to institute appropriate therapy with intravenous infusions, antibiotics and other required medicaments when medical therapy of evacuation of the pyometra affected bitch is undertaken (Nagar et al., 2008; Hagman, 2018), References Antonov AL, Atanasoy AS, Fasulkov IR, Georgiev PI, Yotov SA, Karadaev MP, Vasilev NY (2015), Influence of some factors on the incidence of pyometra in the bitch. Bulgarian J Vet Med: 18: 367-372, 16Journal of Canine Development & Research 2020 Amold S, Reichler I and Hubler M(2006). 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Kleintier Verstegen J, Dhaliwal G and Onclin KV (2008), praxis. 48; 679.683 ‘Mucometra, cystic endometrial byperplasia, and Wheaton LG and Barbee D (1993) . Comparison of two pyometa in the bitch: Advances in treatment dosages of prostaglandin F20t on canine uter- and assessment of future reproductive success ine mobility. Theriogenology 40: 111-120. ‘Theriogenology 70: 364-374, ON JOURNAL OF CANINE DEVELOPMENT AND RESEARCH SUBSCRIPTION FORM | The annual subscription (one issue) rates are as under: For Institutions Rs, 1500.00 or USS 150 or £ 90 or DM 180 or Euro 150 I For Vets & Others Rs. 500,00 or US$ 65 or £ 40 or DM 75 or Euro 65 VOLUMES 1 TO 15 ARE ALSO AVAILABLE | Please enroll me as a subscriber and send me the issue of Journal | Tof Canine Development & Research. I am enclosing herewith I Va Demand Draft No. wuss. Dated aac j towards the annual subscription for the volume I in favour of the CANINE PUBLISHING HOUSE, BIKNAER. 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