Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

POLYPEPTIDE HORMONES
Clinical applications
● To promote contraction of uterine smooth muscle to
assist vaginal birth, to induce uterine evacuation in
metritis and to assist uterine contraction following
reduction of uterine prolapse.
● To promote milk let-down in bitches with adequate
milk production.
Formulations and dose rates
Induction of uterine smooth muscle contraction (for dystocia,
uterine evacuation or postpartum uterine contraction)
• Oxytocin is available as purifi ed, pH adjusted or synthetic forms
of the hormone for parenteral administration. A synthetic form
is also available for intranasal administration.
• Doses recommended have ranged from 0.25–4 IU or 1–5 IU per
bitch to 5–20 IU per bitch, repeated up to three times. In the
queen, 2 IU maximum per queen and per injection IM or by IV
infusion.
• It is important to use calcium gluconate 10% solution
(1 mL/5.5 kg SC q.4–6 h) minimum 15 min before oxytocin
even in eucalcemic bitches. If one treatment of oxytocin for
dystocia is unsuccessful, repeated use must be questioned,
given the likelihood of inducing tetanic uterine contraction and
fetal death.
• There are no data supporting any specifi c regimen for use in
dystocia. Indeed, since absolute oxytocin defi ciency has not
been demonstrated in the parturient bitch or queen, it is diffi cult
to make a rational argument for its use.
For milk let-down
• In bitches with adequate milk production, milk let-down may be
stimulated with intranasal oxytocin. There is little experimental
evidence to support this protocol.
Pharmacokinetics
Oxytocin must be given parenterally because it is
destroyed in the gastrointestinal tract. Onset of activity
is 5 min after IM administration. Duration of activity is
13 min after IV bolus and 20 min after SC or IM
administration.
Oxytocin is metabolized by the liver and kidneys and
a circulating enzyme, oxytocinase, can destroy the
hormone. A small amount is excreted unchanged in urine.
The half-life is 3–5 min in humans and 20 min in goats.
Adverse effects
● Use in obstructive dystocia can cause uterine
rupture.
● Overdose, either single large doses or multiple doses,
will cause spastic, hypertonic or tetanic uterine
muscle contraction with lack of orchestration of contractions.
This may induce placental separation or
damage without delivery, fetal distress or death and
uterine rupture.
● Water intoxication is possible with large
overdosage.
Contraindications and precautions
Oxytocin is widely overused and used in inappropriate
situations.
● Obstructive dystocia.
● Any contraindication for vaginal delivery (e.g.
relative or absolute oversize).
● Maternal toxemia.
● Underlying causes of dystocia (e.g. hypocalcemia)
should be treated before use of oxytocin.
Known drug interactions
● Incompatible with fibrinolysin, noradrenaline (norepinephrine)
bitartrate, prochlorperazine edisylate
and warfarin sodium.
● If used with sympathomimetic agents, can result in
postpartum hypertension.
Dopamine agonists and
serotonin antagonists
Prolactin is a 198-amino acid glycoprotein synthesized
by the lactotrophs of the adenohypophysis. Prolactin
synthesis in pregnancy (from day 25–30 post-LH surge)
and the postpartum period induces mammary development
and lactation.
Prolactin is one of two luteotrophs in the dog (along
with LH). Hypothalamic dopamine has inhibitory
control over prolactin secretion at the pituitary level, so
dopamine agonists inhibit prolactin secretion and dopamine
antagonists such as the antiemetic domperidone
(see Chapter 19) may increase prolactin secretion,
resulting in gynecomastia. Serotonin inhibits dopamine
secretion at the hypothalamus and therefore indirectly
stimulates prolactin secretion.
EXAMPLES
Dopamine agonists act on D 2 -dopamine receptors of the
lactotrophic cells of the pituitary gland.
• Cabergoline (approved in Europe but not Australia, New
Zealand or the United States)
• Bromocriptine
Antiserotoninergic compounds
• Metergoline. This compound also exerts a direct
dopaminergic effect at high doses.
Mechanism of action
Cabergoline is a specific dopamine agonist. Bromocriptine
mesylate is a synthetic ergot alkaloid derivative
which, like cabergoline, directly inhibits prolactin by its
action of D 2 pituitary receptors. Metergoline is a serotonin
antagonist, which increases dopamine-inhibiting
tone at the hypothalamus.
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