Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

EICOSANOID FATTY ACIDS
Contraindications and precautions
● Estrogens should not be used: in diestrus, in pregnancy
or prior to the use of exogenous progesterone
in intact females.
● Administration of DES and estrogens during pregnancy
causes fetal malformations of the urogenital
system.
● Some estrogens are carcinogenic at low levels in
laboratory animals.
Known drug interactions
● Rifampicin (rifampin) administered concurrently
with estrogens may decrease estrogen activity
by inducing microsomal enzyme activity and increasing
estrogen metabolism.
● Oral anticoagulant activity may be decreased by concurrent
administration of estrogens.
● Concurrent use of estrogens with glucocorticoids
may increase glucocorticoid effects.
Antiestrogens
EXAMPLES
Clomifene actetate, tamoxifen acetate.
Mechanism of action
Most antiestrogenic drugs are receptor blockers, such
as clomifene and tamoxifen citrate. However, they may
also induce an estrogenic response, due to their partial
agonist effect. The relative estrogenic-antiestrogenic
effect depends on the species, organ and tissue considered.
In bitches, tamoxifen seems to act predominantly
as an estrogen agonist.
Clinical applications
The potential for tamoxifen to be effective in treatment
of prostatic diseases in dogs is currently under investigation
though its use remains experimental at present.
Formulations and dose rates
• Tamoxifen (2.5 mg/kg daily PO for 28 d) has been successfully
used experimentally to reduce prostatic volume and testosterone
concentration in dogs. A lower dose of 0.3 mg/kg daily PO
for 30 d signifi cantly reduced prostatic size. In the future,
tamoxifen may have therapeutic applications in male dogs
Adverse effects
● Endometritis, pyometra and ovarian cysts developed
in 9/20 bitches treated with tamoxifen (1 mg/kg PO
q.12 h).
● Other side effects are vulvar swelling, vaginal discharge
and urinary incontinence.
Dexamethasone
See Chapter 11 for further information on
dexamethasone.
Clinical applications
Oral dexamethasone has been advocated as an
abortifacient.
Just before parturition or before a cesarean section,
late-term glucocorticoids may enhance the viability of
pups by enhancing the maturation of fetal lungs, as has
been shown to occur in humans. However there are no
data yet to confirm this hypothesis.
Formulations and dose rates
Abortifacient
• Beginning on day 30 post-LH surge, dexamethasone
0.2 mg/kg/d PO q.12 h for 9.5 d decreasing from 0.16 to
0.022 mg/kg over the last fi ve administrations is 100%
effi cacious in terminating pregnancy 7–15 d after the start of
treatment
Adverse effects
With the dosing regimen described in the previous
section, adverse effects were mild and included only
transient and reversible polydipsia and polyuria.
EICOSANOID FATTY ACIDS
Endogenous eicosanoids relevant to reproduction
include members of the prostaglandin (PG) family,
which in turn belong to a family of acidic lipids whose
basic structure is a 20-carbon unsaturated carboxylic
acid. PGs are synthesized from available arachidonic
acid derived from cell membrane phospholipids. Cyclooxygenase
is necessary to transform arachidonic acid
to PGs relevant to reproduction. Nonsteroidal antiinflammatory
drugs inhibit cyclo-oxygenase. Corticosteroids
block PG synthesis by inhibiting release of
arachidonic acid from cell phospholipids.
Prostaglandin F 2a and derivatives
PGF 2α is present in seminal plasma, is luteolytic and
causes contraction of uterine smooth muscle. In farm
animal species, PGF 2α is synthesized in the uterine endometrium
and released in late diestrus and at parturition,
causing luteolyis (CL regression). Luteolysis occurs in
these species as a result of cell death and an antisteroidogenesis
effect mediated by protein kinase C. The
role of PGF 2α in luteolysis in carnivores is poorly
understood.
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