Evaluation of the Risk/Benefit Ratio of Old and New Anti-Inflammatory Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are a structurally diverse group of similarly acting compounds that are widely prescribed and used for the management of pain associated with inflammatory conditions. Our present aim is to choose a leading drug for each class of NSAIDs, and to discuss the debated issues still pending about that drug, in order to weigh the risk/benefit ratio according to the current hypotheses on its mode of action. The leading compounds of the past and present which we have selected within this framework are aspirin, acetaminophen, celecoxib and rofecoxib. The discovery of nitric oxide (NO) in the last decade has resulted in proposing new NO-donors. Particularly interesting in this area has been the synthesis of NO-releasing anti-inflammatory drugs. The addition of NO to aspirin and to other NSAIDs has resulted in molecules that maintain their inhibitory effects on the cyclooxygenases (COX) but are devoid of cardiovascular, renal and gastrointestinal toxicity. The purpose of this review is also to update the “state-of-theart” of new classes of anti-inflammatory drugs such as COX-inhibiting nitric oxide donors (CINODs) and carbon monoxide (CO) releasing molecules (CO-RMs) as future tools in the therapy of inflammation and cellular proliferation.