Page 318 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

296 PART III Therapeutic Modalities for the Cancer Patient

administration. Intraoperative “microdose” ketamine, adminis- of controlled, clinical trials specifically evaluating the efficacy of
tered intravenously (IV), appears to provide beneficial effects for a antidepressants in treating cancer pain, 140 with the exception of
two studies demonstrating a lack of efficacy in the treatment of
variety of oncologic surgical procedures, including limb amputa-
VetBooks.ir tions, 129 and this may reduce the incidence of chronic pain later. chemotherapy-induced peripheral neuropathy. 141,142
The tricyclic antidepressant amitriptyline appears to be effec-
Other reports suggest a benefit to using ketamine perioperatively
in low doses, 130 and the authors recommend its use in cancer sur- tive in cats for pain alleviation in interstitial cystitis, 143 and many
gery to help control pain later postoperatively. practitioners are reporting efficacy in other chronically painful
Amantadine has been used for the treatment of neuropathic conditions in the cat, including OA. Amitriptyline has been used
pain in humans, 131 and one study suggests a benefit to adding daily for periods up to 1 year for interstitial cystitis, and few side
amantadine to an NSAID treatment in dogs that do not get com- effects are reported. The authors have also used amitriptyline in
plete relief from the NSAID alone. 132 The toxic side effects have cats for cancer pain, with some encouraging results. Only two
been evaluated in dogs but not cats, and the dosages suggested case reports have been documented on the use of oral amitrip-
are considered safe. 133 Amantadine should be avoided in patients tyline for neuropathic pain in dogs (dosages of 1.1 mg/kg and
with congestive heart failure, a history of seizures, or those on 1.3 mg/kg PO were used); the reports described improvement in
selegiline, sertraline, or tricyclic antidepressants. the patients’ clinical signs after long-term administration (longer
The active metabolite of dextromethorphan may not be pro- than 3 months). 144 In dogs, pharmacokinetic analyses have shown
duced in dogs, probably negating its use in that species for chronic that oral administration of amitriptyline at a dosage of 4 mg/kg
pain. 134 produces low amitriptyline plasma concentrations, suggesting that
this dosage is an inappropriate therapeutic option for dogs. 145
Anticonvulsant Drugs More experimental and clinical comparative analyses are needed
to validate amitriptyline as a safe and clinically relevant therapeu-
Many anticonvulsants (e.g., carbamazepine, phenytoin, baclofen, tic option in veterinary medicine. Amitriptyline probably should
and more recently, gabapentin) have been used to treat chronic not be used concurrently with other drugs that modify the sero-
pain, including neuropathic pain, in humans, in addition to tonergic system (e.g., amantadine, tramadol) until more is known
chemotherapy-induced peripheral neuropathies. Gabapentin and about drug interactions.
pregabalin are among the most effective drugs available for neuro-
pathic pain in humans. Although the exact mechanism of action Sodium Channel Blockade
of these drugs is unclear, one potential mode by which they exert
their analgesic effect is by binding to the α -δ protein subunit Alterations in the level of expression, cellular localization, and dis-
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of voltage-gated calcium channels, thereby reducing excitatory tribution of sodium channels are seen in many pain states. These
neurotransmitter release through channel modulation or chan- aberrantly expressed sodium channels result in hyperexcitability
nel trafficking. Although considerable information is available on and ectopic activity in peripheral and central nerves that encode
gabapentin disposition in dogs and cats, 135–138 and some informa- nociceptive information. Low doses of lidocaine and other sodium
tion has been reported on its use as an anticonvulsant in dogs, 139 channel blockers readily block these aberrantly expressed sodium
no information has been produced about its use for the control of channels, producing pain relief. Low-dose IV lidocaine has proven
chronic or long-term pain. as effective as other commonly used medications for the treatment
A potential analgesic value can be attributed to gabapentin (and of neuropathic pain in humans, 146 and the author (BDXL) uses
theoretically to pregabalin). Although the indications for gaba- such an approach to downregulate central sensitization in veteri-
pentin and pregabalin presently are unclear in veterinary patients, nary cancer patients. The use of transdermal lidocaine patches for
these drugs do appear to be useful for cancer pain in some patients the treatment of cancer pain is attracting increasing interest. 147
and are probably particularly effective in cancers that have some Much of this interest revolves around using the patch to admin-
neurogenic or nerve destruction component. However, further ister a low systemic level of lidocaine that blocks the aberrantly
clinical trials are required to assess the efficacy of these drugs in expressed sodium channels. Studies have been performed evalu-
domestic animals. ating the kinetics of lidocaine absorbed from patches applied to
dogs and cats. 148–150 Peak plasma concentrations of lidocaine were
Tricyclic Antidepressants obtained between 10 and 24 hours after application in dogs and
at 65 hours after application in cats. The results of these studies
Tricyclic antidepressants have been used for many years for the indicate that, similar to what is seen in humans, systemic absorp-
treatment of chronic pain syndromes in people and are becom- tion of lidocaine from the patch is minimal. Potential systemic
ing widely used for the modulation of behavioral disorders in toxicity associated with lidocaine administration, including bra-
animals. Within the CNS are descending inhibitory serotonergic dycardia, hypotension, cardiac arrest, muscle or facial twitching,
and noradrenergic pathways that reduce pain transmission in the tremors, seizures, nausea, and vomiting, was not noted in any
spinal cord. Tricyclic antidepressants (e.g., amitriptyline, clomip- study. Dosing guidelines have been suggested, 151 although to date
ramine, fluoxetine, imipramine, maprotiline, and paroxetine) no reports have been published evaluating the analgesic efficacy
primarily inhibit the reuptake of various monoamines (serotonin of topical lidocaine (whether in patches or cream) in veterinary
for clomipramine, fluoxetine, and paroxetine; noradrenaline for cancer patients; however, the technique holds promise.
imipramine, amitriptyline, and maprotiline). Tricyclic antidepres-
sants can also interact directly with 5-hydroxytryptamine and Steroids
peripheral noradrenergic receptors and may also contribute other
actions, such as voltage-gated sodium channel blockade and reduc- Glucocorticoids provide an effective strategy for counteract-
tion in peripheral prostaglandin E -like activity or tumor necrosis ing inflammatory pain. The mechanism of actions of steroids
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factor production. However, human medicine has a relative lack involves inhibition of collagenase and proinflammatory cytokines.