Page 181 - The Welfare of Cattle

158 the WeLfare of CattLe

PharMaCOLOGY OF aNaLGeSIC DrUGS

The use of pharmaceuticals as analgesic is an important factor in the treatment and well-being
of animals. However, it is important to recognize the challenges and factors that must go into utiliz-
ing these agents for pain mitigation, especially in food producing animals. First is the regulatory
component of using these drugs. As of July 2017, there is only one compound with a label for pain
mitigation in the United States. Furthermore, this compound, flunixin meglumine transdermal, is
only approved for the treatment of pain associated with foot rot in cattle. Beyond the one drug for
one disease condition, there are no other drug approvals for pain mitigation in cattle. The Animal
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Medicinal Drug Use Clarification Act (AMDUCA) of 1994 permits extra-label drug use (ELDU) in
order to relieve suffering in cattle. As such, analgesics would be permitted under AMDUCA given
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the criteria for ELDU are followed. This requires a valid veterinary–client–patient relationship
(VCPR) and the prescribing veterinarian must ensure the ELDU does not result in violative drug
residues in meat or milk.
The basic pharmacology of the commonly used and researched analgesic compounds will be
discussed in the remainder of this section before discussion of individual procedures or disease
conditions.

Local anesthesia

Local anesthetics are the most commonly used analgesics in cattle. They function by block-
ing sodium channels within nerve cells and preventing the conduction and transmission of the
pain signal. By blocking the nerve transmissions, the regions innervated by the nerves are devoid
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of sensation. Additionally, nerve fibers responsible for pain and temperature are blocked before
those fibers are involved with touch, pressure, and motor activity. The addition of vasoconstric-
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tors (e.g., epinephrine) to the local block increase contact time to the nerve and prolong the length
of desensitization. Onset of activity for lidocaine, a common local anesthetic agent, is rapid, with
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desensitization lasting about 90 minutes. Other local anesthetics in veterinary medicine include
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bupivacaine, which has a longer duration but also is slower to onset of action. 5
Non-steroidal anti-inflammatory Drugs (NSaIDs)

The mode of action for NSAIDs is the inhibition of cyclo-oxygenase (COX) isoenzymes and
subsequent reduction in the production of prostaglandins (PGs) from arachidonic acid. PGs con-
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tribute to the inflammatory response through recruitment of inflammatory cells, vasodilation, and
working in concert with other cytokines and neuropeptides. All these actions result in the reduction
of the action potential threshold in nociceptors and propagation of the pain signal. Peripherally, PG
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production causes local hyperalgesia or peripheral sensitization; centrally excess PG lead to central
sensitization and chronic pain. Both COX-1 and COX-2 isoenzymes are thought to be responsible
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for the inflammatory response, with the initial effects a result of COX-1 derived PG and the delayed
effects due to upregulation of COX-2 expression. For immediate and prolonged pain control, an
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NSAID targeting both isoenzymes may be advantageous as inhibition of COX-1 is associated with
renal and gastrointestinal effects. 6

Flunixin Meglumine

Flunixin meglumine is derived from nicotinic acid in the anthranilic acid NSAID class. Flunixin
is the only FDA-approved NSAID for cattle in the United States and is the only NSAID with a
label approval for the treatment of pain. There are two approved formulations of flunixin in the