NSAIDs for acute and chronic pain management (Proceedings)


NSAIDs for acute and chronic pain management (Proceedings)

Nov 01, 2010

Use of analgesics prior to surgery (preemptive analgesia) may also be beneficial. Non-steroidal anti-inflammatory drugs are commonly being administered during the perioperative period. Debate exists as to when to administer the drugs (preoperatively vs. postoperatively). Since intraoperative hypotension is always possible, the author prefers to administer NSAIDs during or after surgery once adequate perfusion pressures have been assured during anesthesia. While data exists to support the safe use of preoperative NSAIDs in healthy patients undergoing relatively short periods of anesthesia, if the approach of reducing risk during anesthesia is taken, it is rational to wait until surgery is nearing completion before administering NSAIDs.

Chronic administration of NSAIDs is common practice in dogs for the symptomatic treatment of osteoarthritis, neoplastic conditions, and a multitude of other ailments. Chronic NSAID prescribing in cats is done, however there are no currently FDA-CVM approved NSAIDs for repeated dosing in cats and use in this manner is extra-label. Informed consent of the owners should be obtained before initiating extra-label drug use in any species. Additionally, while the quality of life of many cats has likely been improved using chronic NSAID dosing, the incidence of adverse events is not know with any degree of certainty therefore determining the risk vs. benefit must be made on an individual basis. Anytime chronic NSAID administration is prescribed a baseline CBC, serum chemistry, and urinalysis would seem prudent since subclinical disease may be present, especially in older animals or animals with co-morbidities.

Analgesic Agents
Non-steroidal anti-inflammatory drugs continue to be the mainstay of acute and chronic pain management in both human and veterinary patients. Traditionally, it has been believed that the analgesic effects of NSAIDs are related to their ability to inhibit cyclooxygenase activity and prevent prostaglandin synthesis and peripheral nociceptor sensitization. However, there is considerable evidence that at least some NSAIDs have a central spinal site of action, and may act synergistically with other analgesic compounds.

Concurrent use of corticosteroids and other NSAIDs such as aspirin are generally not recommended due to the expected increase rates of adverse events. When switching NSAIDs a washout period is also commonly recommended. The recommended interval is usually on the order of 3-7 days, however; some have recommended washout periods of <1 day based on pharmacokinetic characteristics of the NSAIDs approved for use in dogs. In the author's opinion, the interval should be established on a case-by-case basis and consideration should be given to the animals co-morbidities, reason for switching (e.g., lack of effectiveness vs. toxicity), the patient's quality of life without NSAIDs, availability of alternative analgesic classes, and the veterinarian/owner's willingness to accept adverse events.

Adverse drug reactions to NSAIDs are common. There are significant species differences in the pharmacokinetics of most NSAIDs and drugs approved for use in one species should not be used in another without careful verification of dosing information. Human approved NSAIDs are usually not the drug of choice for veterinary species and clients should be educated of their dangers. The most common adverse effect in dogs is gastrointestinal upset with the potential for erosion or ulceration. This is believed to occur because of direct mucosal irritation related to the dosage formulation (unbuffered aspirin) or from altered mucosal blood flow secondary to inhibition of prostaglandins. Gastrointestinal ulceration occurs mainly in the stomach but can occur in the small intestine. Some clinicians will co-administer H-2 blockers, proton pump inhibitors, sucralafate, or synthetic prostaglandins such as misoprostil to try to prevent, or reduce the signs of gastrointestinal side effects in patients at risk of developing ulcers. NSAID administration to animals predisposed to gastrointestinal ulceration should not be done routinely. Animals on concurrent steroid therapy, with gastrointestinal disease, animals that are not eating, and animals that are under stress are predisposed to gastrointestinal ulceration.

Renal damage is a less common, but potentially life threatening side effect of NSAIDs in most species. The mechanism of renal failure is thought to be impairment of renal blood flow associated with loss of vasodilatory prostaglandins in the kidney. Usually the first sign of renal tissue damage is elevation of urine enzymes, but later serum BUN and creatinine increase. Patients that have periods of poor renal perfusion, are on nephrotoxic drugs, or that have a history of renal disease are not good candidates and are at potentially greater risk for NSAID-associated toxicity. NSAID administration to patients receiving diuretics may inhibit diuretic action. The mechanism appears to be related to reduced glomerular blood flow.

Most NSAIDs will inhibit platelet function. The duration of the inhibited function varies with the drug. It is longest for aspirin and shortest for "reversible inhibitors" of COX such as carprofen. Aspirin irreversibly binds to COX and will require synthesis of new enzyme before platelet function returns. This can take several days and many clinicians are not comfortable performing elective procedures sooner than 7-10 days after the last dose of aspirin. This is most troublesome for procedures that are associated with difficult hemostasis such as neurosurgery. It is not a good idea to administer aspirin to a dog presenting with intervertebral disk disease in case emergency surgery is required.

Idiosyncratic reactions to most NSAIDs have been reported. These reactions are usually due to a pharmacogenetic interaction and are usually not predictable. The best-known reaction is hepatopathy associated with the administration of carprofen to dogs. Others include hypoproteinemia and KCS associated with etodolac and bone marrow dyscrasias associated with phenylbutazone.