nsaids gout dr. bangayan

• What is the term used to describe the inflammatory process?

  Rheumarampa
• What are the noxious agents that can trigger an inflammatory process?


  • Infections
  • Antibodies
  • Trauma
• What are the cardinal signs of inflammation?


  • Calor (heat)
  • Dolor (pain)
  • Rubor (redness)
  • Tumor (swelling)
  • Function Laesa (loss of function)
• What are the phases of the inflammatory process?

  1. Acute: Transient vasodilation, increased capillary permeability
  2. Subacute: Infiltration of leukocytes and phagocytic cells
  3. Proliferative: Tissue degeneration and fibrosis
• What is the role of endothelial activation in inflammation?


  It involves the expression of selectins and integrins that facilitate leukocyte recruitment.
• What are the key mediators involved in inflammatory cell recruitment (chemotaxis)?

  • C5a
  • PAF
  • LTB4
• What are the pro-inflammatory mediators mentioned in the study material?

  • IL1(α, ß)
  • TNF(α, ß)
  • IL2
  • IL6
  • IL8
  • GM-CSF
  • TGF-ß
  • IL10
  • IFN-γ
• What are some other mediators of inflammation?


  • Histamine
  • Bradykinin
  • Leukotrienes
  • Serotonin
  • Substance P
  • Prostaglandin
• What is the role of membrane phospholipids in inflammation?


  • They are precursors for various inflammatory mediators.
  • They are converted to HPETE and other mediators.
• What is the mechanism of action of NSAIDs?


  They are synthetic inhibitors of the COX active site.
• What is unique about aspirin compared to other NSAIDs?


  Aspirin is the only covalent, irreversible modifier of COX-1 and COX-2.
• What are the pharmacokinetics of NSAIDs?


  • Weak organic acids (except Nabumetone)
  • Mostly racemic mixtures (except Naproxen)
  • Well absorbed; food does not change bioavailability
  • Highly metabolized in the liver
  • 98% protein bound (albumin)
• What is the final elimination route for NSAIDs?


  Renal elimination.
• What are some clinical uses of NSAIDs?


  • Systemic Mastocytosis
  • Bartter’s Syndrome
  • Cancer Chemoprevention
  • Niacin Tolerability
• What are the adverse effects of NSAIDs?


  • GI irritant
  • Nephrotoxic
  • Hepatotoxic
  • Central Nervous System effects
  • Cardiovascular issues
• What is the pKa of salicylic acid?
• What is the pKa of acetylsalicylic acid?


  3.5
• What is the mechanism of action of aspirin?


  • Irreversibly inhibits platelet COX
  • Antiplatelet effect lasts 8–10 days
  • Duration of action in other tissues is 6–12 hours
• What are the adverse effects of aspirin?


  • Gastric upset
  • Gastric and duodenal ulcers
  • Hepatotoxicity
  • Asthma
  • Rashes
• What is the half-life of aspirin?


  15 minutes.
• What are the special precautions for salicylic acids?


  • Decrease dose by 50% in renal failure and hepatic insufficiency.
• What are the pharmacokinetics of non-acetylated salicylates?


  • Do not inhibit platelet aggregation.
  • Preferable when COX inhibition is undesirable.
• What are the characteristics of COX-2 selective inhibitors?


  • Do not affect platelet function.
  • Lesser GI complications.
  • Increased risk of edema, hypertension, myocardial infarction.
• What is the significance of celecoxib?


  • 10–20 times more selective for COX-2 than COX-1.
  • Fewer endoscopic ulcers than most other NSAIDs.
  • Significant interaction with warfarin.
• What is the significance of meloxicam?


  • Preferentially selective for COX-2.
  • Fewer clinical GI symptoms than other NSAIDs.
• What are the characteristics of diclofenac?


  • Less frequent gastrointestinal ulceration.
  • Can impair renal blood flow and GFR.
  • Available in various formulations (ophthalmic, topical, etc.).
• What are the characteristics of ibuprofen?


  • Equivalent to 4 g of aspirin in anti-inflammatory effect.
  • Effective in closing patent ductus arteriosus in preterm infants.
  • Relative contraindications include nasal polyps and angioedema.
• What are the characteristics of ketoprofen?


  • Inhibits both COX and lipoxygenase.
  • Probenecid increases ketoprofen levels.
• What are the characteristics of etodolac?


  • Racemic acetic acid derivative.
  • Recommended dose in OA and RA is 300 mg twice or three times a day.
• What are the characteristics of naproxen?


  • The only NSAID marketed as a single enantiomer.
  • Rare cases of allergic pneumonitis and leukocytoclastic vasculitis.
• What are the characteristics of nabumetone?


  • The only nonacid NSAID.
  • Given as a ketone prodrug with a half-life of more than 24 hours.
• What are the characteristics of oxaprozin?


  • Very long half-life (50–60 hours).
  • Mildly uricosuric.
• What are the characteristics of flurbiprofen?


  • More complex mechanism of action than other NSAIDs.
  • Rarely associated with cogwheel rigidity and ataxia.
• What are the characteristics of meclofenamate and mefenamic acid?


  • Both are fenamic acids.
  • Used for pain relief.
• What are the characteristics of sulindac?


  • Decrease dose in renal and liver disease.
  • Approved for treatment of PDA.
• What are the characteristics of ketorolac?


  • Decrease dose by 50% with renal insufficiency.
  • Used for short-term management of moderate to severe pain.
• What are the characteristics of tolmetin?


  • Not effective in gout.
  • Administered four times a day.
• What are the characteristics of fenoprofen?


  • More frequent idiosyncratic nephropathy.
  • Administered four times a day.
• What are the characteristics of indomethacin?


  • Approved for treatment of PDA.
  • Administered three times a day.
• What are the characteristics of diclofenac and misoprostol combination?


  • Used to reduce gastrointestinal side effects.
  • Can cause diarrhea as an adverse reaction.