Lsn 15: Nonsteroidal Anti-Inflammatory Drug (NSAID's)

• Understand the inflammation mechanism of action initiated by arachidonic acid (phospholipid release of arachidonic acid, generation of prostaglandins and thromboxanes through cyclooxygenase pathway, generation of leukotrienes through lipoxygenase mechanism)
• Understand the mechanism of action of cyclooxygenase (COX) inhibitors
• Identify key structural features of NSAIDs and understand of specific important interactions with COX enzymes
• Understand the specific interaction between the NSAID carboxylic group  and the COX Arg-120 side chain; describe and effectively explain the effect upon K_m values that occur when neutral glutamine is substituted for Arg-120

Understand and clearly discuss aspirin's unique mechanism of action for irreversible COX inhibition
• COX-2 Inhibitors
• Understand key differences between COX-1 and COX-2 enzymes, their physiological roles, and their respective inhibitors
• Clearly describe the rationale for the development of COX-2 inhibitors
• Explain the structure differences between nonspecific COX inhibitors and COX-2 specific inhibitors; relate these differences to active site geometries of thee two enzymes
• Use COX-1 and COX-2 IC50 values for various substances to evaluate their respective potential for therapeutic development