Analgesic

• Analgesics

  For Pain
• Analgesics

  • Non narcotic
  • Narcotic
• Paracetamol


  • MOA: Inhibits COX3 in the brain
  • Weak inhibitor of COX in the periphery
• Toxic dose of paracetamol

  4 g / day
• Lethal dose of paracetamol

  15 g / day
• Factors that enhance paracetamol toxicity

  • Liver disease
  • Enzyme inducer
• Stages of paracetamol toxicity


  1. I. Nausea

  2. II. Abnormal Lab result (↑ ALT, ↑ AST, Creatinine)

  3. III. Comatose

  4. IV. Recovery
• Antidote for paracetamol toxicity

  1. Acetylcysteine
• Inflammation


  A normal, protective response to tissue injury caused by: physical trauma, noxious chemical, microbiologic agents
• Inappropriate activation of our immune system


  Can result in inflammation leading to rheumatoid arthritis (RA)
• Rheumatoid Arthritis


  Autoimmune disorder with inflammation in the synovial membrane lining of the joint, resulting in progressive joint destruction, deformity and disability
• Age of onset of rheumatoid arthritis

  40 and 60, more common in women than men
• Etiology of rheumatoid arthritis


  • Bacterial or viral infection
  • Genetic markers - triggers and propagates RA
  • Inflammed synovium - hallmark of RA
• Osteoarthritis


  Degenerative joint disease due to excessive wear and tear of joint
• Signs and symptoms of osteoarthritis


  • Joint pain, stiffness at rest or immobility, mild inflammation, crepitus
• Classification of anti-inflammatory agents


  • Salicylates
  • Pyralozone derivatives
  • Indole derivatives
  • Phenyl acetic acid derivatives
  • Oxicam derivatives
  • Fenamates
  • Propionic Acid Derivatives
  • Selective COX-2 inhibitors
  • NSAIDS
  • DMARDs
  • Non narcotic Analgesic
  • Acetaminophen
  • Immunosuppressants
  • Antimalarials
  • Gold preparations
  • Penicillamine
  • Leflunomide
  • Etanercept
  • Infliximab
  • Anakinra
  • Anti gout
• NSAIDS


  Non-steroidal anti-inflammatory agents with anti-inflammatory, antipyretic and analgesic properties
• MOA of NSAIDS


  • Inhibit cyclooxygenase enzyme
• Salicylates


  Aspirin is the prototype drug, 15% of the population are intolerant, they irreversibly acetylate/inactivate COX
• Diflunisal


  Active in itself, not metabolized to salicylates, no anti pyretic activity
• Sulfasalazine


  Converted to 5 -Aminosalicylic acid, used for IBD or Crohn's disease
• Therapeutic uses of salicylates


  • Antipyretics and analgesics
  • Keratolytic
  • Colon cancer
• ADRs of salicylates


  • GI intolerance, Erosive gastritis
  • Prolongs bleeding time
  • Increase alveolar ventilation and respiration at therapeutic doses, Respiratory paralysis at toxic doses
  • Hyperglycemia, glycosuria, decreased lipogenesis
• Salicylism

  Tinnitus, nausea and vomiting
• Reye's Syndrome


  Fatal fulminating hepatitis with cerebral edema
• Pyrazolone derivatives


  Phenylbutazone, Dipyrone, Oxyphenbutazone, Sulfinpyrazone - used as anti-inflammatory agents only
• ADRs of pyrazolone derivatives

  • Hematotoxic
  • Nephrotoxic
  • Hepatotoxic
• Drug interactions of pyrazolone derivatives

  Can displace other drugs from plasma proteins, Goitrogenic drug (Phenylbutazone)
• Indomethacin


  Indole derivative, more potent than aspirin as an anti-inflammatory agent, can cause frontal headache
• Clinical uses of indomethacin

  • PDA
  • Acute gouty arthritis
  • Ankylosing spondylitis
• Diclofenac, Alcofenac, Sulindac


  Phenylacetic acid derivatives, Sulindac is a sulfur containing drug, indicated for osteoarthritis and ankylosing spondylitis
• Ketorolac


  Phenylacetic acid derivative, mild anti-inflammatory effect, used as analgesic in post op pain
• Piroxicam


  Oxicam derivative, long half life, used for rheumatoid arthritis, osteoarthritis, spondylitis
• Mefenamic Acid

  Fenamate, has analgesic property with very little anti-inflammatory property, must be given for not more than 5 days, not given to children
• Propionic acid derivatives

  • Ibuprofen
  • Naproxen
  • Ketoprofen
• Side effects of propionic acid derivatives

  • Nephrotoxicity and GI irritation
• Selective COX2 inhibitors

  • Etoricoxib
  • Parecoxib
  • Lumiracoxib
• Advantage of selective COX2 inhibitors

  Well tolerated
• Acetaminophen


  Non narcotic analgesic, MOA: Weak prostaglandin inhibitor in periphery, inhibits prostaglandin synthesis in the CNS
• Toxic metabolite of acetaminophen


  NAPQI (N-acetyl paraquinone)