NSAIDS GOUT

• What is the prototype of the salicylates and other NSAIDs?


  Aspirin (acetylsalicylic acid)
• How do older nonselective NSAIDs primarily vary?


  In their potency, analgesic and anti-inflammatory effectiveness, and duration of action
• Which NSAID has greater anti-inflammatory effectiveness than ibuprofen and naproxen?


  Indomethacin
• What was the purpose of developing COX-2-selective inhibitors?


  To lessen gastrointestinal toxicity while preserving efficacy
• What is a significant risk associated with highly selective COX-2 inhibitors compared to nonselective drugs?


  A higher incidence of cardiovascular thrombotic events
• What does cyclooxygenase convert arachidonic acid into?


  Endoperoxide precursors of prostaglandins
• Where is COX-1 primarily expressed?


  In noninflammatory cells
• What is the primary effect of aspirin and nonselective NSAIDs on cyclooxygenase isoforms?


  They inhibit both COX-1 and COX-2
• How does the mechanism of action of aspirin differ from other NSAIDs?


  Aspirin irreversibly inhibits cyclooxygenase, while other NSAIDs inhibit it reversibly
• What is the antipyretic action of cyclooxygenase inhibitors attributed to?


  Suppression of prostaglandin synthesis in the CNS stimulated by pyrogens
• What are the three therapeutic dose ranges for aspirin?


  Low (<300 mg/d), intermediate (300–2400 mg/d), high (2400–4000 mg/d)
• What happens to the half-life of salicylate at high doses?


  It increases to 15 hours or more and elimination becomes zero order
• What is the half-life of ibuprofen?


  About 2 hours
• For what conditions are other NSAIDs commonly used?


  Mild to moderate pain, dysmenorrhea, headache, and patent ductus arteriosus in premature infants
• What is the most common adverse effect of therapeutic doses of aspirin?


  Gastric upset
• What serious condition can develop in children treated with aspirin during a viral infection?

  Reye’s syndrome
• What is a significant risk associated with the use of parenteral ketorolac?


  Gastrointestinal and renal damage with longer administration
• What is the mechanism of toxicity for acetaminophen in overdose?


  Oxidation to cytotoxic intermediates by phase I cytochrome P450 enzymes
• What is the half-life of acetaminophen in persons with normal hepatic function?


  2–3 hours
• What are the key differences between NSAIDs and acetaminophen?


  • NSAIDs: Anti-inflammatory, analgesic, and antipyretic effects
  • Acetaminophen: Analgesic and antipyretic, lacks anti-inflammatory effects
• What are the therapeutic uses of NSAIDs and acetaminophen?

  • NSAIDs: Pain relief, inflammation reduction, fever reduction
  • Acetaminophen: Pain relief, fever reduction, especially in children and aspirin intolerance
• What are the potential toxicities associated with NSAIDs?


  • Gastric upset and ulceration
  • Renal damage
  • Increased bleeding time
  • Risk of cardiovascular events with COX-2 inhibitors
• What are the mechanisms of action for NSAIDs and acetaminophen?

  • NSAIDs: Inhibit cyclooxygenase, reducing prostaglandin synthesis
  • Acetaminophen: Weak COX inhibitor, may inhibit COX-3 in CNS
• What are the classifications of drugs used in rheumatoid arthritis and gout?

  • NSAIDs
  • Acetaminophen
  • DMARDs (conventional and biologic)
  • Uricosurics
  • Xanthine oxidase inhibitors
• What type of effects does acetaminophen lack?


  Anti-inflammatory or antiplatelet effects
• For what indications is acetaminophen effective?


  It is effective for the same indications as intermediate-dose aspirin
• In which populations is acetaminophen particularly useful as an aspirin substitute?


  In children with viral infections and those with aspirin intolerance
• How is acetaminophen absorbed and metabolized?


  It is well absorbed orally and metabolized in the liver
• How does renal disease affect the half-life of acetaminophen?


  The half-life is unaffected by renal disease
• What is the toxicity of acetaminophen at therapeutic dosages?


  It has negligible toxicity in most persons
• What happens when acetaminophen is taken in overdose or by patients with severe liver impairment?


  It becomes a dangerous hepatotoxin
• What is the mechanism of acetaminophen toxicity?


  Oxidation to cytotoxic intermediates by phase I cytochrome P450 enzymes
• When does acetaminophen toxicity occur?


  If substrates for phase II conjugation reactions are lacking
• What is the lifesaving treatment after an acetaminophen overdose?

  Administration of acetylcysteine
• Who is at increased risk of acetaminophen-induced hepatotoxicity?


  People who regularly consume 3 or more alcoholic drinks per day
• What are the characteristics of Disease-Modifying Antirheumatic Drugs (DMARDs)?

  • Heterogeneous group of agents
  • Anti-inflammatory actions in connective tissue diseases
  • Slow down or reverse joint damage
  • Effects may take 6 weeks to 6 months to become apparent
• What is the classification of DMARDs based on?


  They are classified based on their anti-inflammatory actions
• What are some common adverse effects of DMARDs?


  • Infection
  • Hepatotoxicity
  • Nephrotoxicity
  • Gastrointestinal disturbances
  • Rash
• What is the role of corticosteroids in the treatment of severe disease?


  They are reserved for temporary control of severe exacerbations
• How do cytotoxic drugs like methotrexate work in treating rheumatoid arthritis?


  They reduce the number of immune cells maintaining the inflammatory response