Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

STEROIDS
acromegaly and adrenocortical suppression. High
doses of progestins or repeated or prolonged exposure
to moderate doses of progestins may: increase
the incidence of uterine pathology, including the
CEH-pyometra complex; increase secretion of growth
hormone and thus the risk of acromegalic changes;
increase the risk of local skin alterations when
administered parenterally and promote weight gain.
Their role in promoting mammary tumors after prolonged
use remains unclear. For all these reasons,
repeated progestin treatments are not recommended
in females, especially in breeding bitches.
● Progestins at high doses given to male dogs (MPA
20 mg/kg SC; MA 4 mg/kg PO daily for 7 d) cause
reduced sperm quality (which may be irreversible if
sufficiently high doses are used for long periods) but
do not affect libido.
● Delmadinone has a suppressive effect on both libido
and spermatogenesis and return to normal function
following use of delmadinone in male dogs is
unpredictable.
Contraindications and precautions
● All progestins are contraindicated in pregnancy, diestrus,
following estrogen administration and in
animals with diabetes mellitus, mammary neoplasia
or endometrial disease.
● Progestins should be used with care in any animal
that will subsequently be used for breeding.
Known drug interactions
● Progestins in combination with corticosteroids may
exacerbate adrenocortical suppression and diabetes
mellitus.
● Estrogens will induce progesterone receptors on the
endometrium so concurrent or prior use of estrogens
with progestins is more likely to precipitate cystic
endometrial hyperplasia.
Antiprogestins
EXAMPLES
The antiprogestin compounds that have been tested in
small animal reproduction are mifepristone (RU 486) and
aglepristone (RU 534).
Mechanism of action
Antiprogestins are synthetic steroids which have a high
affinity for progesterone receptors, preventing progesterone
from exerting its biological effects. They act as
true receptor antagonists, preventing the uterine effects
of progesterone without initially decreasing serum progesterone
concentrations. The affinity of aglepristone
for uterine receptors is three times greater than that of
progesterone itself. Progesterone concentrations after
treatment only decline to less than 3 nmol/L from 8 to
34 d. This may be due to premature luteolysis caused
by increased endogeneous PGF 2α .
Clinical applications
● Pregnancy termination in bitches and queens.
● Medical treatment of pyometra.
● Induction of parturition.
● Planning of an elective cesarean section.
● Treatment of feline mammary fibroadenomatosis.
● Treatment of hypersomatotropism (acromegaly).
There are only preliminary experimental studies
supporting this potential use.
Formulations and dose rates
Aglepristone is available as an injectable formulation in oil.
IN BITCHES
Pregnancy termination
• Aglepristone 10 mg/kg SC given twice, 24 h apart, is the
recommended dose. Aglepristone can be used from the fi rst to
the 45th day of mating. However, it is preferable, to avoid
failure due to a premature treatment, to wait until the end of
estrus to use the protocol described above. Treatment before
25 d after mating results in nearly 100% in utero embryonic
resorption. Treatment from 25 d after mating may lead to
induced abortion within 7 d, with a prolonged vaginal discharge,
mammary development and maternal behavior patterns. The
effectiveness of aglepristone-induced abortion after 25 d is
approximately 95%. To avoid in vivo intrauterine fetal
mummifi cation the manufacturer does not recommend induced
abortion after 45 d of pregnancy. The interestrus intervals
following induced abortion are usually signifi cantly reduced by
1–3 months. Treatment does not seem to affect future
reproduction in the aborted bitch.
Medical treatment of pyometra
In bitches with pyometra and serum progesterone levels above 1–
2 ng/mL, aglepristone treatment causes the uterine cervix to open
and uterine contractions, resulting in discharge of uterine contents
and reduction of endometrial size. Broad-spectrum systemic antibacterials
must be administered concurrently during the treatment period
to prevent septicemia and any other related complications. When the
pyometra has resolved, it is recommended to breed the bitch at the
subsequent cycle to prevent recurrence. Aglepristone may be used in
combination with prostaglandins or alone
• Combination of aglepristone and PGF 2a . Most protocols
recommend the use of aglepristone 10 mg/kg at day 1 (d1), d2,
d8, d15 (with a fi nal treatment on d29 if some vulvar discharge
still persists). There are various dosing schedules for PGF 2α
when used with aglepristone: cloprostenol (1 µg/kg SC daily
from d3 to d7, or 1 µg/kg SC on d3 and d8), dinoprost (25 µg/
kg SC three times daily, d3 to d7, or 25 µg/kg d3,d6 and d9).
The addition of cloprostenol to the aglepristone therapy,
compared with aglepristone alone, signifi cantly improved the
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