How many of your patients chronically take non-steroidal anti-inflammatory drugs (NSAIDs)? In a recent Saskatchewan survey, approximately 13% of the general population had filled a prescription for an NSAID during the preceding year. In British Columbia these drugs accounted for 6.4% of total claims and 9.8% of drug cost to the Pharmacare Program.
This frequent prescribing reflects the benefit derived from NSAIDs in the symptomatic relief of arthritis and other conditions. Yet, although most patients tolerate this group of drugs well, serious and sometimes fatal reactions have been reported. Patients receiving long-term non-steroidal anti-inflammatory drug treatment should be carefully monitored. We review the gastrointestinal, renal, hepatic, and hematologic adverse effects associated with NSAID therapy and recommend preventive measures and monitoring protocols for patients at risk.
All non-steroidal anti-inflammatory drugs exhibit dose-related inhibition of the enzyme cyclooxygenase, resulting in decreased prostaglandin synthesis. Non-steroidal anti-inflammatory drugs can thereby decrease inflammation, pain, and fever. The inhibition of cyclooxygenase is reversible for all NSAIDs except acetylsalicylic acid, so prostaglandin-related effects should be rapidly reversible in most cases. But other mechanisms of toxicity also exist.
Non-steroidal anti-inflammatory drugs share several basic pharmacokinetic properties: high plasma albumin binding (99%), hepatic metabolism, and the excretion of a small amount unchanged by the kidneys. Hypoalbuminemia, liver dysfunction, and reduced renal function can therefore place patients at risk for increased plasma levels and toxicity.
While reduced albumin concentration, liver function, and renal function are all associated with aging, in general, the pharmacokinetics of non-steroidal anti-inflammatory drugs are not changed significantly in the elderly. Age-related decreases in clearance have been reported for piroxicam, naproxen, and ketoprofen, but the clinical relevance is unknown.
Half-lives were not prolonged in the elderly in studies with ibuprofen and diclofenac. Low doses of NSAIDs should be used in any patient with compromised liver function. Patients with poor renal function should be prescribed selected non-steroidal anti-inflammatory drugs, keeping in mind that renal dysfunction increases the risk of renal toxicity (see Renal problems).