The COX-2 Selective NSAIDs
The COX-2 Selective NSAIDs
Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed groups of drugs worldwide and are highly effective as analgesic, antipyretic and anti-inflammatory agents. However, drugs of this class are responsible for substantial morbidity and mortality as a result of the complications associated with gastroduodenal ulcers, such as perforation and bleeding.
The central mechanism of the NSAIDs, which accounts for their therapeutic effects and their gastroduodenal toxicity, is their ability to inhibit prostaglandin synthesis. Recognition that there are 2 isoforms of the enzyme cyclooxygenase (COX) responsible for prostaglandin synthesis has enabled the development of drugs capable of sparing the gastric mucosa. While the majority of traditional NSAIDs are nonselective inhibitors of COX, some are thought to be preferential inhibitors of COX-2, at least at low dosages (e.g. meloxicam, nimesulide, etodolac).
Two drugs that are claimed to be highly selective or specific in their ability to inhibit COX-2 while having little or no COX-1 affinity are rofecoxib and celecoxib. These selective NSAIDs reduce the pain and inflammation associated with rheumatoid arthritis and osteoarthritis. However, they produce a level of gastroduodenal injury that is similar or equivalent to that seen with placebo, whereas high rates of damage and ulceration are seen with nonselective NSAIDs. Before this promise can be confirmed, more experience will be needed with these agents. In addition, COX-2 inhibitors share the adverse effects of NSAIDs outside the gastrointestinal tract that are dependant on COX-2 inhibition.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed groups of drugs worldwide and are highly effective as analgesic, antipyretic and anti-inflammatory agents. However, drugs of this class are responsible for substantial morbidity and mortality as a result of the complications associated with gastroduodenal ulcers, such as perforation and bleeding.
The central mechanism of the NSAIDs, which accounts for their therapeutic effects and their gastroduodenal toxicity, is their ability to inhibit prostaglandin synthesis. Recognition that there are 2 isoforms of the enzyme cyclooxygenase (COX) responsible for prostaglandin synthesis has enabled the development of drugs capable of sparing the gastric mucosa. While the majority of traditional NSAIDs are nonselective inhibitors of COX, some are thought to be preferential inhibitors of COX-2, at least at low dosages (e.g. meloxicam, nimesulide, etodolac).
Two drugs that are claimed to be highly selective or specific in their ability to inhibit COX-2 while having little or no COX-1 affinity are rofecoxib and celecoxib. These selective NSAIDs reduce the pain and inflammation associated with rheumatoid arthritis and osteoarthritis. However, they produce a level of gastroduodenal injury that is similar or equivalent to that seen with placebo, whereas high rates of damage and ulceration are seen with nonselective NSAIDs. Before this promise can be confirmed, more experience will be needed with these agents. In addition, COX-2 inhibitors share the adverse effects of NSAIDs outside the gastrointestinal tract that are dependant on COX-2 inhibition.
Source...