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for induction of abortion, as such combined treatments are shorter and more efficacious. Care should be taken to make sure that the cervix is open, as causing uterine contractions on a closed cervix may cause uterine rupture or force uterine content up into the oviducts. Therefore, aglepristone is administered first and then PGF are used once cervical opening has occurred.
Other clinical applications
Prostaglandin F2a (PGF) products have been used
also to induce parturition (albeit with a continuous infusion pump) in 57-day pregnant bitches with whelping occurring normally within 2-3 days14. A shortening of the interstrous interval may be obtained using PGF alone
or in combination with antiprolactinics. The use of a 6-10 day course of PGF starting after day 10 of cytological diestrus will achieve a complete luteolysis which will shorten diestrus and very often also anestrus. We have observed bitches in which a complete and permanent luteolysis was obtained with PGF early in their luteal phase coming back in heat after 70-90 days following the onset of previous proestrus5. If shortening of the duration of diestrus is obtained with PGF and is then followed by an antiprolactinic treatment (which may shorten anestrus – see over), the interestrous interval will be substantially shortened. In male dogs, an increase in semen volume and occasionally also quality (often motility) may be obtained by administration of PGF at the dose of 100 mcg/kg 15 minutes prior to semen collection; this has resulted in an increase of 270% of total sperm numbers when compared to saline treated controls, with no deleterious effect on refrigeration and freezing (Hess, 2006). PGF may also be used to obtain an ejaculate from a reluctant or inexperienced dog15.
Prostaglandin E1 - A synthetic analogue of PGE1, misoprostol, has a strong uterotonic action and may
be used to help evacuating uterine content in bitches and queens with pyometra. Misoprostol is marketed
as a human compound under different trade names
and is available in 200 mcg tablets. In the bitch it is administered at 10 mcg/kg BID orally (1/2 tablets/10 kg16. It is very well tolerated and may be administered at home by clients. It has no luteolytic properties and little if any side effects mostly on the first day of treatment (vomiting = 25% of cases; diarrhoea = 30% of cases) 17. It can be used in both bitches and queens as an adjunct to a PGF2a or aglepristone treatment to improve uterine contractility, or to continue causing uterine contractions once luteolysis has been accomplished thus sparing the female the PGF2a related side effects. PGE1 pills may also be dissolved in saline solution and administered intravaginally 18.
ANTIPROLACTINICS
Prolactin secretion by the lactotroph cells of the anterior pituitary gland is regulated by multiple neuro-
transmitters and hormones, with the major control mechanism being the activation of prolactin-inhibiting dopaminergic neurons in the hypothalamus. Prolactin
is a major luteotrophic hormone and appears to be an absolute requirement for canine and feline progesterone secretion from day 30 after ovulation onwards. Dopamine agonists like bromocriptine or cabergoline
are ergot alkaloids, with strong dopamine D2-receptor agonist activity, and thus can reduce prolactin secretion thereby suppressing progesterone levels. The serotonin antagonist metergoline indirectly stimulates endogenous dopamine secretion and thus can inhibit prolactin secretion as well. Cabergoline has a slow clearance, which allows for a single oral daily administration. Furthermore, its action when used at the currently accepted dosage of 5 mcg/kg is longer than 48 hours due to its particularly long (minimum 48 hours) half-life at the hypophyseal level. Bromocryptine mesylate inhibits PRL secretion during relatively short periods of time (half- life: ± 4-6 hours) and in a dose-dependent mode. In order to effectively inhibit PRL tone in a continuous fashion
for therapeutic purposes, bromocryptine should be administered at least twice a day orally at doses 10-50 mcg/kg. Its lack of specificity leads to side effects on the cardiorespiratory system, causing hypotension due to vasodilatation (adrenergic type effect), or emesis due to stimulation of the Chemioreceptive Trigger Zone (CTZ). Although its effectiveness has never been questioned, bromocryptine is not approved in most countries as an anti-PRL in small animals and its use in animals may be prosecuted in countries where veterinary antiprolactinic drugs are available. Metergoline is essentially a serotoninergic antagonist with dopaminergic agonist properties when used orally at doses of 0.1-0.2 mg/kg BID. Its shorter half-life requires at least administrations twice a day. Its antiserotoninergic properties may occasionally induce central effects such as depression, nervousness, increased excitability, changes in appetite (anorexia or bulimia), psychotic effects (escaping
from home, rarely aggressiveness), rarely vomition. Antiprolactinic drugs can be used in the bitch and the queen with three indications: pseudopregnancy, induction of abortion and induction of estrus 19.
Pseudopregnancy
Antiprolactinics are currently considered the treatment of choice for pseudopregnancy. The anti-lactogenic action of both metergoline and cabergoline is well known19. Their administration for 4-5 days at pharmacological doses is effective in treating pseudopregnancy signs and reducing milk production. Occasional failures can
be dealt with by repeating the treatment protocol and extending it to 8 to 10 days, and also by administering at the same time metergoline (at the usual antigalactogenic dosage of 200 mcg/kg BID). Our current approach is
to prescribe a 6-8 day treatment course as we feel that this decreases incidence of recurrence. Because
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