Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CLASSES OF SEDATIVE/TRANQUILIZER
output. Reversal with a specific α 2 -receptor antagonist
is a more appropriate treatment for severe α 2 -
agonist-induced bradycardia.
● The influence of α 2 -agonists on catecholamineinduced
arrhythmias is controversial. Early studies
showed that xylazine reduced the threshold for
adrenaline (epinephrine)-induced arrhythmias in
anesthetized dogs. However, a later study, investigating
the effects of xylazine and medetomidine, failed
to demonstrate a proarrhythmic effect with either
agent. The effect of dexmedetomidine on cardiac
rhythm is less contentious. Studies have demonstrated
an antiarrhythmic effect, possibly mediated
through interaction with imidazoline receptors.
Respiratory effects
The respiratory effects of α 2 -agonists vary in severity
between species.
● In dogs and cats, minute ventilation tends to fall,
primarily as a consequence of reduced respiratory
rate, but changes in arterial blood gases are usually
slight. A proportion of patients appear cyanotic and
this has been observed in the absence of major reductions
in the arterial partial pressure of oxygen. It has
been suggested that the cyanosis reflects venous
desaturation as a consequence of increased oxygen
extraction by the tissues. Whatever the cause, such
patients should receive supplemental oxygen.
● More severe alterations in arterial blood gases,
including overt hypoxemia, have been documented
in ruminants, particularly sheep, sedated with α 2 -
agonists. Mismatching of pulmonary ventilation and
perfusion is the most likely cause. Acute pulmonary
edema has also been reported following xylazine use
in small ruminants. Although the mechanism is
unknown, factors such as pre-existing pathology,
pulmonary hypertension, altered capillary permeability
and free radical generation may contribute.
● Anecdotal reports suggest that acute pulmonary
edema may occur, albeit infrequently, in small animal
patients as well.
Gastrointestinal effects
● Vomiting is a frequent occurrence following intramuscular
administration of α 2 -agonists. It is most
common with xylazine, especially in cats, in which
the incidence may approach 50%. It is mediated
centrally through direct activation of receptors in the
chemoreceptor trigger zone.
● Overall, α 2 -agonists depress gastrointestinal motility
and prolong gut transit times. This parasympatholytic
effect has been attributed to reduced release of
acetylcholine from cholinergic nerve terminals innervating
the gastrointestinal tract. Reductions in salivary
and gastric secretions may also occur.
● In dogs, xylazine has been shown to reduce gastroesophageal
sphincter tone, which may increase the
risk of gastric reflux.
● Gastric distension is an additional adverse effect that
has been recorded in large breed dogs. It is not clear
how it arises. It may simply be a consequence of
gastrointestinal atony leading to accumulation of gas
or alternatively aerophagia may be involved.
Endocrine effects
● α 2 -Agonists exert a variety of effects on endocrine
function. Of most significance are reductions in the
release of insulin and antidiuretic hormone. Inhibition
of insulin release is mediated via α 2 -receptors on
the β-cells of the pancreas and the result is hyperglycemia
and glycosuria. Pancreatitis has been observed
in experimental cats following repeated IM administration
of high doses of romifidine. The mechanism
involved is not clear.
● Diuresis also occurs, primarily as a consequence of
reduced ADH release, although glycosuria may
contribute.
● Transient alterations in growth hormone, tes -
tosterone, prolactin and FSH have also been
reported.
Effects in pregnancy
● Uterine contractility may be modified by α 2 -agonists.
The effects of medetomidine in the pregnant bitch
appear to be dose dependent. While low doses
decrease uterine electrical activity, higher doses
(≥40 µg/kg) have a transient stimulatory effect.
● Definitive evidence that α 2 -agonists increase the
incidence of abortion or obstetrical complications is
lacking. Nonetheless, their use in pregnant patients
cannot be recommended.
Contraindications and precautions
α 2 -Adrenoceptor agonists can only be recommended for
use in young healthy patients. Contraindications include
the following.
● Patients with myocardial disease or reduced cardiac
reserve
● Hypotension and shock
● Respiratory disease
● Hepatic insufficiency
● Renal dysfunction
● Diabetes mellitus
● Any sick/debilitated patient
● Pregnancy.
Romifidine may increase blood urea concentrations in
cats and attention to fluid balance is recommended.
Known drug interactions
● α 2 -Agonists act synergistically with opioid analgesics.
The use of such combinations allows the dose
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