Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 23 DRUGS AND REPRODUCTION
Clinical applications
● Galactostasis: dopamine agonists will prevent
prolactin secretion and indirectly impede milk
production.
● Overt pseudocyesis or pseudopregnancy: bitches
exhibiting these signs have high peripheral prolactin
concentrations, which can be treated with dopamine
agonists.
● Pregnancy termination: dopamine agonists given systemically
or orally during pregnancy, after day 30–40
post-LH surge, may induce abortion. Oral cabergoline
or bromocriptine may be combined with cloprostenol
(a synthetic prostaglandin analog) to reduce
the dose of both drugs in the bitch and queen.
● Estrus induction and reduced interestrus interval: the
action of dopamine agonists is not fully understood.
They do not act only by reducing the level of serum
prolactin. They may also directly stimulate the hypothalamic
pituitary axis. Cabergoline and bromocriptine
will reduce the interval between estrus by
shortening both diestrus and anestrus, possibly by a
dopaminergic action that is not related to the suppression
of prolactin secretion. However:
– the duration of treatment for estrus induction is
much shorter in late versus early anestrus;
– estrus induction in diestrus is unlikely to lead to
a successful pregnancy, probably due to lack of
uterine endometrial regeneration.
● Treatment of pyometra.
● Pretreatment of mammary tumors.
Formulations and dose rates
Galactostasis and pseudocyesis
• Cabergoline: 5 µg/kg/d PO for 5–10 d
• Bromocriptine: 50–100 µg/kg PO for 10–14 d. To reduce side
effects, the dose can be given q.8–12 h. Dopamine receptors
play an important role in the vomiting pathway (see Chapter
19). The emetic effect can be attenuated by gradually
increasing the dose: 2.5 µg/kg q.12 h day 1, 5 µg/kg q.12 h
day 2 and 10 µg/kg q.12 h day 3–5 or 3–10
• Metergoline: 0.1 mg/kg PO q.12 h for 8–10 d. Minimum 8 d
required
Pregnancy termination in the bitch
• Cabergoline: 5 µg/kg/d PO for 5 d or 1.7µg/kg SC every 2 d for
6 d will induce abortion in 100% of bitches treated from 40 d
post-LH surge, but only 25% of bitches from day 30
• Cabergoline (5 µg/kg/day PO for 10 d) plus cloprostenol (1 µg/
kg/48 h SC for fi ve injections) from day 28 post-LH surge will
induce abortion in > 95% of bitches
• Bromocriptine at doses of 50–100 µg/kg PO twice a day for at
least 5 and up to 10 d is not consistently effective in inducing
abortion before day 40. This treatment should never be
discontinued until termination of pregnancy has been
confi rmed. It is never effective before day 30
Pregnancy termination in the queen
• Use of dopaminergic drugs alone is not recommended for early
pregnancy termination in queens, as variable effi cacy is
reported. However, after 40 d of pregnancy, cabergoline (5 µg/
kg/d for 7 d) or bromocriptine (25–50 µg/kg q.8 h for 7d) will
result in pregnancy termination, often associated with fetal
expulsion. Combined treatment with PGF 2α begins earlier, on
day 25 after fi rst breeding. Abortion can be induced using three
injections of cloprostenol (5 µg/kg) at 48-h intervals (d1, d3 and
d5) associated with a daily oral administration of cabergoline
(5 µg/kg for 7–10 d). This treatment does not lead to any side
effect.
Estrus induction in bitches
• Dopamine agonists (bromocriptine, cabergoline) have been used
successfully to induce estrus in bitches. Cabergoline-induced
cycles have follicular development and ovulatory rates similar to
those observed at natural cycles. However, if the level of estrus
induction is high, regardless of the period of treatment within
the estrous cycle, the stage of treatment appears to be
important. Fertile estrus is more reliably obtained if the bitch is
treated during late anestrus. Bromocriptine (250 µg/kg/d until
proestrus occurred) induced a fertile estrus in 5/6 bitches.
Cabergoline 5 µg/kg/d induces estrus within 30 d, with 75–85%
whelping rate. In cases of prolonged anestrus ( >8 months),
daily treatment for 3 weeks with oral cabergoline (5 µg/kg)
induced fertile estrus within one month in 70% of treated
bitches.
Treatment of pyometra in bitches
• Combination treatment with oral cabergoline (5 µg/kg daily) and
cloprostenol (5 µg/kg every third day) has been used to treat
pyometra medically (in addition to appropriate antibacterial
therapy) in bitches. Resolution was achieved in 21 of 22 treated
bitches within 13 d. 11/21 bitches were mated at the next
estrus and conceived. Cabergoline (5 µg/kg PO daily) and
cloprostenol (1 µg/kg daily SC) for 7–14 d were also successful
in 24/29 bitches
Treatment of pyometra in queens
• Cabergoline (5 µg/kg PO daily) and cloprostenol (1 µg/kg SC
daily) until complete uterine emptying (in addition to appropriate
antibacterial therapy) has been recommended
Pretreatment of mammary tumors
• Most mammary tumors are detected and surgically treated
during diestrus when the mammary gland is enlarged and often
partially fi lled with milk. Treatment with cabergoline 5–7 d
before surgery will facilitate the surgical procedure because (a)
mammary tumors can be more accurately palpated because the
mammary gland is not enlarged, (b) there is reduced risk of a
postsurgical reaction because milk does not contaminate the
surgical site and (c) the bitch or queen recovers more quickly
because the surgery is faster and the duration of anesthesia
reduced. Furthermore, due to the decreased progesteronemia, it
has been postulated that there may be a higher immunity in the
operated bitch or queen
Pharmacokinetics
The duration of activity of bromocriptine in the dog is
only about 8 h; in humans it has a biphasic half-life (4 h
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