Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 23 DRUGS AND REPRODUCTION
Formulations and dose rates—cont’d
For all these reasons, eCG is not recommended for use in
bitches or queens.
Challenge testing for ovarian tissue
• This test may be used in cases where ovarian remnant
syndrome in spayed females is suspected.
• hCG 100–1000 IU (bitch) or 50–100 IU (queen) IM when
showing estrus signs and measure peripheral progesterone in
5–7 d. Progesterone above 1 ng/mL is consistent with
functional ovarian tissue.
Luteinization of follicular cysts
• hCG 500 IU per dog IM and repeat in 48 h. However, as
discussed previously, veterinarians must be aware that when
there has been prolonged estrogen secretion by an ovarian cyst,
GnRH treatment may lead to a CEH-pyometra. It is highly
recommended that the bitch be spayed or treated with an
antiprogestin compound (aglepristone) just after GnRH
treatment.
Estrus induction in anestrus queens (many different protocols
have been described)
• The preferred treatment is: eCG (100–150 IU IM) followed 5 d
later by 1–3 daily injections of hCG (50–100 UI IM). This
treatment leads to ovulation and pregnancy results similar to
those observed with natural matings (over 80%)
Ovulation induction in queens
• 50–200 IU hCG at the peak of estrus. Ovulation generally occurs
24–36 h after injection
IN MALES
Challenge testing for testicular tissue
• hCG: 50 µg/kg (dog) or 250 µg (cat) IM. Measure serum
testosterone concentration immediately before and 4 h after
hCG.
Cryptorchidism treatment
• hCG: 500 IU per dog IM twice weekly for 4–6 weeks or 50 IU/kg
IM every 2 d for 10 d followed by no treatment for 10 d, then
50 IU/kg IM every 2 d for 10 d. Animals should be aged less
than 4 months at the beginning of treatment. The success rate
is not defi ned, as most studies do not include any control
group. In reality, there is no good evidence to support this
treatment approach.
Stimulation of spermatogenesis
• FSH and eCG have been promoted as appropriate for use as
stimulators of spermatogenesis, with or without concurrent
hCG. There are no conclusive data to support this
recommendation.
Pharmacokinetics
● FSH, eCG: no specific information is available.
● hCG: peak plasma levels at 6 h. Biphasic elimination
from blood: the initial elimination half-life is 11 h
and terminal elimination half-life is 23 h.
Adverse effects
● Repeated injections of exogenous gonadotropins
may lead to the production of antibodies against
FSH or LH, which may cross-react with the endogenous
and exogenous hormones and lead to a subsequent
decreased response to stimulation or subsequent
infertility.
● FSH and PMSG: undesired superovulation, follicular
cysts and cystic endometrial hyperplasia mediated by
steroid production are possible and are more likely
with higher doses and repeated administration.
● hCG:
– Hypersensitivity
– In humans, injection site pain, gynecomastia,
headache, depression, irritability and edema have
been reported.
Contraindications and precautions
● FSH and eCG
– Do not use in bitches with cystic endometrial
hyperplasia.
– Adverse effects are likely to be exacerbated if
gonadotropins are given concurrently with exogenous
sex steroids or in the face of high levels of
endogenous sex steroids.
● hCG: none reported.
Known drug interactions
None reported, but use of gonadotropins concurrently
with sex steroids is likely to promote cystic endometrial
hyperplasia in females.
Oxytocin
Oxytocin is a nonapeptide hormone synthesized in the
hypothalamus and stored in the posterior pituitary
gland. Oxytocin mediates contractility of the endometrium
which has been prestimulated with estradiol. It
stimulates contractility of the myoepithelial cells that
surround mammary alveoli. It is measured in USP posterior
pituitary units, where 1 unit = 2.0–2.2 mg of pure
hormone.
Mechanism of action
Oxytocin causes contraction of uterine smooth muscle
by increasing the sodium permeability of the uterine
myofibrils. Presence of high peripheral estrogen levels
reduces the threshold for oxytocin-induced smooth
muscle contraction. A dose of 1 IU oxytocin IV (per
bitch) will induce intrauterine pressure of over
100 mmHg in a pre-estrous bitch and 58 mmHg in an
anestrous bitch, demonstrating that it is still active in
the absence of estrogen.
Oxytocin facilitates some milk let-down without
having galactopoietic ability. It is mildly antidiuretic.
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