Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 23 DRUGS AND REPRODUCTION
EXAMPLES
Dinoprost tromethamine is the tromethamine (THAM) salt
of naturally occurring PGF 2α . Cloprostenol is a synthetic
analog of the F-class.
Mechanism of action
PGF 2α causes myometrial contraction, cervical relaxation
and luteolysis in several species. Its specific mechanism
of action in carnivores is poorly understood.
Clinical applications
● Abortion induction in the bitch and queen.
● Treatment of pyometra in the bitch and queen.
● Reduction of the duration of interestrus intervals.
Formulations and dose rates
Abortion in the bitch
• Natural or synthetic PGF 2α is rarely capable of inducing
luteolysis in early pregnancy (before day 15–20).
• However, high doses (150–250 µg/kg q.12 h for 4–5 d) may be
successfully used around day 15–25 of pregnancy. Lower
doses (20 µg/kg q.8 h) around 20–21 d after ovulation induced
abortion in 5/5 bitches
• Use of natural PGF 2α : in mid-pregnancy (around day 30),
abortion can be successfully induced using:
– moderate doses: 30–50 µg/kg q.12 h for 5–9 d
– increasing doses: starting 30–50 µg/kg then increasing to
100–200 µg/kg after several days
– high doses: 200–250 µg/kg q.12 h for 4–7 d.
• However, side effects (emesis, salivation, defecation, respiratory
distress) are often induced when using a high dose from the
start of the treatment period. To avoid this a suggested protocol
is repeated injections q.8–12 h, for 7 d or longer, initially using
low doses (25 µg/kg) for 1 or 2 d, increasing to doses of 50 µg/
kg and then increasing again to doses of 100 µg/kg after 4 d if
higher doses are well tolerated by the bitch.
• Cloprostenol has been proved to be an effi cient abortive agent:
2.5 µg/kg 3 injections at 48-h intervals after d25 of pregnancy.
Abortion in the queen
• Dinoprost 0.5–1.0 mg/kg SC once and repeated in 48 h will
result in abortion (after d40) within 8–24 h. The protocol might
work earlier in gestation, especially at higher and more frequent
dosing, but is more reliable from d40 as the CL in the cat and
dog is quite resistant to the effect of PGF prior to mid-gestation.
• Natural prostaglandins are better tolerated by queens than by
dogs. Doses of up to 0.5 mg/kg q.8–12 h for 5 d may be used
Treatment of pyometra in the bitch
• Dinoprost (0.01–0.1 mg/kg q.8–12 h SC) until both uterine
evacuation has occurred and serum progesterone is basal. The
dose of dinoprost may be reduced by including cabergoline
(5 µg/kg/d PO) in the regimen.
Treatment of pyometra in the queen
• Dinoprost 0.1 mg/kg SC on d1 then 0.25 mg/kg/d SC for 5 d,
re-evaluate in 2 weeks and retreat if necessary. Lower doses of
dinoprost (0.01–0.05 mg/kg SC q.4–6 h for 5–10 d) were well
tolerated and proved effi cient for treating pyometra in queens.
In the majority of treated queens, uterine size decreased by
50% in 72–96 h.
Reduction of the duration of interestrus intervals in the bitch
• The use of long-acting PGF 2α fenprostalen (one injection SC 25 d
after ovulation) signifi cantly shortened the time to subsequent
estrus by a mean of 80 d, with a normal conception rate.
Pharmacokinetics
In rats, dinoprost distributes very rapidly to tissues and
has a serum half-life of minutes in cattle. No information
is available on cloprostenol.
Adverse effects
● Dinoprost and cloprostenol may cause:
– abdominal pain
– emesis
– defecation
– urination
– pupillary dilation followed by constriction
– tachycardia
– restlessness and anxiety
– fever
– hypersalivation
– restlessness and panting.
● Adverse effects appear within 5–120 min and may
last 20–30 min.
● Adverse effects are dose dependent, with the dinoprost
LD 50 being 5.13 mg/kg SC in the bitch.
● Prior atropine administration may attenuate adverse
effects. Concurrent administration of atropine,
metopimazine and prifinium bromide 15–20 minutes
prior to prostaglandins administration has been proposed,
by some authors, to reduce side effects.
Butylscopolamine, when available, may also be an
effective adjuvant therapy to reduce side effects of
PGF 2α .
● Fatalities have been reported. The authors do not
recommend use of either natural or synthetic PGF 2α
in English bulldogs, as this breed often reacts
adversely to these drugs, with serious side effects and
sometimes death.
Contraindications and precautions
● PGF 2α and synthetic analogs are contraindicated
during pregnancy or in animals with hepatic, renal
or systemic disease.
● Do not administer intravenously.
● Pregnant women or people with bronchial disease,
including asthma, should not handle or administer
these drugs.
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