Chapter 38: Pharmacotherapy of Inflammation, Fever, Pain, and Gout

INTRODUCTION

This chapter describes the non-steroidal anti-inflammatory drugs (NSAIDs) used to treat inflammation, pain, and fever and the drugs used for hyperuricemia and gout. The NSAIDs are first considered by class, then by groups of chemically similar agents described in more detail. Many of the basic properties of these drugs are summarized in Tables 38–1, 38–2, and 38–3.

The NSAIDs act by inhibiting the prostaglandin (PG) G/H synthase enzymes, colloquially known as the cyclooxygenases (COXs) (see Chapter 37). There are two forms, COX-1 and COX-2. The inhibition of COX-2 is thought to mediate, in large part, the antipyretic, analgesic, and anti-inflammatory actions of NSAIDs. Adverse reactions are largely caused by the inhibition of COX-1 and COX-2 in tissues in which they fulfill physiological functions, such as the GI tract, the kidney, and the cardiovascular system. Aspirin is the only irreversible inhibitor of the COX enzymes in clinical use. All other NSAIDs bind the COXs reversibly and act either by competing directly with arachidonic acid (AA) at the active site of COX-1 and COX-2 or by changing their steric confirmation in a way that alters their ability to bind arachidonic acid. Acetaminophen (paracetamol) is effective as an antipyretic and analgesic agent at typical doses that partly inhibit COXs and has only weak anti-inflammatory activity. Purposefully designed selective inhibitors of COX-2 (celecoxib, etoricoxib) are a subclass of NSAIDs; several of the older traditional NSAIDs, such as diclofenac and meloxicam (see Figure 38–1) also selectively inhibit COX-2 at therapeutic doses.

ABBREVIATIONS

INFLAMMATION, PAIN, AND FEVER

Inflammation

The inflammatory process is the immune system’s protective response to an injurious stimulus. It can be evoked by noxious agents, infections, and physical injuries, which release damage- and pathogen-associated molecules that are recognized by cells charged with immune surveillance (Tang et al., 2012). The ability to mount an inflammatory response is essential for survival in the face of environmental pathogens and injury. In some situations and diseases, inflammation may be exaggerated and sustained without apparent benefit and even with severe adverse consequences (e.g., hypersensitivity, automimmune diseases, chronic inflammation). The inflammatory response is characterized mechanistically by

• transient local vasodilation and increased capillary permeability;

• infiltration ...