NSAIDs

    Cards (21)

    • What does COX stand for in the COX pathway?
      Cyclooxygenase
    • How do prostaglandins affect inflammatory responses?
      They cause swelling, inflammation, pain, and fever
    • What are NSAIDs?
      Non-steroidal anti-inflammatory drugs
    • What is the source of arachidonic acid in the body?
      Degradation of cell membrane phospholipids
    • What are the roles of thromboxane and prostacyclin in platelet aggregation?
      • Thromboxane A2: Induces platelet aggregation
      • Prostacyclin: Inhibits platelet aggregation
    • What is the relationship between arachidonic acid and COX?
      • Arachidonic acid is a substrate for COX
      • COX catalyses conversion of arachidonic acid into prostaglandins
    • What is the significance of NSAIDs in treating inflammation?
      • They inhibit COX enzymes
      • Reduce prostaglandin synthesis
      • Alleviate pain and inflammation
    • Draw the COX pathway:
    • How does the active site of COX relate to its function?
      The active site contains a heme moiety
    • Is Aspirin a non-selective or selective COX Inhibitor?
      Aspirin is a non-selective competitive COX inhibitor - an NSAID
    • How does aspirin inhibit COX enzyme?
      Aspirin covalently bind to a serine residue that is close to heme that the acylation causes a steric block. The heme cannot be accessed by the substrate (arachidonic acid) => the enzyme is rendered inactive
    • What type of interaction do non-selective NSAIDs have with Arg120?
      Ionic interaction
    • What type of inhibition do salicylates exhibit?
      Reversible and competitive inhibition
    • What can outcompete salicylate in the inhibition process?
      Increased concentration of arachidonic acid
    • What is a characteristic of COX-2 selective NSAIDs?
      They have an additional hydrophilic binding site
    • What type of acid do some COX-2 selective NSAIDs utilize?
      Enolic acid
    • How do larger molecules of COX-2 selective NSAIDs affect arachidonic acid access?
      They block the path within the COX channel
    • What functional group binds favorably with the side pocket of COX-2?
      Sulfone or sulfonamide functional group
    • Which compounds are selective for COX-1?
      Thiothers and sulfoxides
    • What are the key structural features of non-selective NSAIDs?
      • Restricted planar: steric bulk, blocking the arachidonic acid from entering thy hydrophobic channel to access the heme active site within COX enzyme. Eg: aromatic substituent - benzene ring
      • Acidic group: form ionic interaction with Arg 120. Eg: Carboxylic acid, COOH - is deprotonated at physiological Ph to form carboxylate
      • Lipophilic group: Eg: phenol, OH => high degree of lipophilicity
    • What are general characteristics of COX-2 selective NSAIDs?
      have an additional hydrophilic binding site e.g sulfones or sulphonamide
      • Any 5 or 6membered ring => larger molecule with restricted conformational freedom
      • 2 aromatic rings
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