Chapter 19 The Prevention and Management of Pain in Canine Patients 487also blocks norepinephrine receptors on blood
vessels, resulting in vasoconstriction. The
resulting hypertension parasympathetically
induces bradycardia, which is extended by a
subsequent direct decrease in sympathetic tone.
Cardiac index is decreased, although central
perfusion is maintained. Many uses are
described for the perioperative setting, usually
in combination with opioids and at doses much
lower than suggested by the manufacturer.
Tips for use
Intravenous microdoses (0.25–1.0 μg/kg)of
dexmedetomidine intra‐ and postoperatively
can address rocky anesthetic episodes, postop
pain, or dysphoria. This calculates to tiny vol-
umes even in large dogs, and although the
effect at these doses may last only 10–15 min-
utes, it may be re‐dosed to effect. CRI doses are
also described (Valtolina et al., 2009). In the
event a concerning degree of bradycardia
arises, anticholinergics (atropine, glycopyro-
late) should be avoided as they will increase
heart rate, against tremendous vascular resist-
ance, with potentially serious consequences.
Instead, atipamezole is used to reverse the
bradycardia.
Other drugs in class
● Tizanadine (Zanaflex®, Sirdalud ®) is an
oral, centrally acting alpha‐2 agonist used in
humans primarily as a skeletal muscle
relaxant to treat muscle spasticity, and the
pain derived from it, in multiple sclerosis
and a variety of other painful conditions. Its
utility in dogs is unknown.
● Clonidine is a centrally acting alpha‐2 ago-
nist that can be administered systemically
via oral, i.v., s.c., i.m., transdermal, and epi-
dural routes. Indicated in humans as anti-
hypertensive agent and to treat ADHD, new
uses are being found for its antinociceptive
effects (Neil, 2011).
Pain‐modifying analgesic drugs
Tramadol (Ultram®) is a popular analgesic that
in humans breaks down into a highly active
mu‐agonist opioid (M1) metabolite along with
a separate metabolite with serotonin and nor-
epinephrine (inhibitory neurotransmitters)
agonism. However, dogs produce very little of
the M1 metabolite (Kögel et al., 2014), and what
little they make has a very short half‐life (1.7
hours) (KuKanich & Papich, 2004). Studies
have demonstrated the clinical usefulness of
parenteral (i.v., i.m., s.c., epidural) tramadol in
dogs (Martins et al., 2010; Seddighi et al., 2009),
although presumptively it would not be elic-
ited via mu agonism but rather via the separate
metabolite that enhances the inhibitory neuro-
transmitters serotonin and norepinephrine.
Although oral tramadol is a popular adjunct to
chronic pain management in humans (Wilder‐
Smith et al., 2001), its pharmacokinetics in dogs
is poor (low plasma levels that decrease to neg-
ligible levels after sequential administration over
several days) (Malek et al., 2012). There is no
strong evidence to suggest any kind of signifi-
cant pain‐modifying effect in dogs. Problems of
abuse and diversion in humans have cause the
FDA to move tramadol to a Schedule IV status.Tips for use
Note that adverse drug effects can include GI
and extrapyramidal effects.Other drugs in class
● Tapentadol (Nucytna®) is a centrally acting
analgesic with a dual mode of action simi-
lar to tramadol: mu‐opioid receptor ago-
nism and inhibition of norepinephrine
reuptake. It is the parent compound, not a
metabolite, that provides both of these
effects, and thus it may offer an alternative
superior to tramadol in dogs. Unfortunately,
recent data reveal low bioavailability in
dogs (only 4%) (Young, 2008; Giorgi et al.,
2012), and poor performance on a tail‐flick
analgesia model (Therapeutic Goods
Administration, 2011). A more recent study
of tapentadol reveals, in contradistinction
to tramadol, analgesia in a canine tail‐flick
model, attributable to an opioid effect of the
parent compound otherwise absent with
tramadol or its metabolites (Kögel et al.,
214). Tapentadol has not been evaluated
clinically in dogs.