Anti-inflammatory & Pain-Reducing Drugs

Inflammation

• Body's Protective Response

  • Cytologic and chemical reactions in affected tissues and blood vessels.
  • Aim to limit damage and prevent microbial invasion.

• 5 Cardinal Signs (Result from chemical signals - prostaglandins, histamine)

  1. Redness
  2. Heat
  3. Swelling
  4. Pain
  5. Loss of Function

Anti-inflammatory Drugs

1. Steroids (Corticosteroids/Glucocorticoids)

• Endogenous Production

  • Produced by adrenal cortex:
    • Cortisol: Main glucocorticoid (many effects)
    • Aldosterone: Main mineralocorticoid (regulates electrolytes)
  • Regulated by negative feedback (steroid drugs mimic this).

• Types of Steroid Drugs

  • Glucocorticoid-only or Corticosteroid (both gluco- and mineralo-).
  • Acting Duration:
    • Short acting (< 12 hr)
    • Intermediate acting (12 – 36 hr)
    • Long acting (> 48 hr)

• Administration Routes:

  • Oral
  • Topical (often with other drugs)
  • Injectable (SQ, IM, IV)

• Adverse Effects:

  • Polyphagia, weight gain
  • Panting (dogs)
  • Behavioral changes
  • Skin/coat changes
  • Muscle wasting
  • Delayed wound healing
  • Increased risk of infection
  • GI ulceration and bleeding
  • Induction of parturition in some species
  • Suppression of endogenous glucocorticoid production
  • Iatrogenic hyperadrenocorticism

• Uses:

  • Inflammation, autoimmune disorders, allergic diseases, Addison’s Disease, certain neoplasms, ketosis in cattle.

• Considerations:

  • Prednisone is converted to prednisolone in the liver; use prednisolone in cats/recovering animals.
  • Prefer topical over systemic use whenever possible.
  • Avoid long-term systemic use; taper off; avoid in pregnant or diabetic animals.
  • Do not use concurrently with NSAIDs.

2. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Mechanism:

  • Prostaglandin inhibitors; inhibit cyclooxygenase (COX) enzymes.
  • May be non-selective (COX-1 & COX-2) or selective (only COX-2).

• Key Features:

  • Anti-inflammatory, anti-pyretic, analgesic properties.
  • Metabolized in the liver (potential hepatotoxicity).

• Adverse Effects:

  • Gastrointestinal issues (vomiting, diarrhea, bleeding, ulceration).
  • Nephrotoxicity.
  • Delay or disruption of parturition.

• Classes of NSAIDs:

  1. Salicylates: Aspirin
     • Nonselective, not FDA approved for vet use, adverse effects include bleeding and GI issues.
  2. Phenylbutazone
     • Nonselective, used in equine medicine, potential adverse effects include necrosis if extravasated.
  3. Propionic Acid Derivatives (-fen drugs)
     • Analgesic, anti-inflammatory; examples: Ibuprofen, Ketoprofen, Carprofen (selective for COX-2; rare hepatotoxicity).
  4. Coxibs and Oxicams:
     • Selective COX-2 inhibitors, ex. Deracoxib, Firocoxib, Robenacoxib (consider renal effects in cats).
  5. Other NSAIDs:
     • Flunixin meglumine (approved for horses, swine, cattle).
     • Diclofenac sodium (topical use approved in horses).
     • Grapiprant (dogs only, antagonizes prostaglandin receptors).

3. Antihistamines

• Role of Histamine:

  • Released by mast cells; causes vasodilation, increased permeability, spasms.

• Mechanism of Antihistamines:

  • H1 receptor antagonists; used for treating pruritus, motion sickness, allergies.

• Examples:

  • Diphenhydramine, Dimenhydrinate, Cetirizine, Cyproheptadine.

4. Other Anti-inflammatory Drugs

• DMSO:

  • Mechanism unclear; used topically, reduces swelling, potential skin irritation, increases absorption of other drugs.

• Immunomodulators:

  • Modify immune response; examples include Cyclosporine, Tacrolimus, Oclacitinib.

5. Analgesics

• Types:

  1. Narcotics (opioids)
  2. Non-narcotics: NSAIDs, acetaminophen.

• Acetaminophen:

  • Toxic to cats; causes methemoglobinemia and hepatotoxicity; treat with N-acetylcysteine.

• Ketamine & NMDA receptor antagonists:

  • Use in severe pain management; adjuncts to traditional therapies.

• Chondroprotective Agents:

  • Glycosaminoglycans, helps maintain cartilage structure, used alongside NSAIDs for chronic pain management (e.g., Legend®, Adequan®).

• Monoclonal Antibodies:

  • Targeting specific mediators of pain in osteoarthritis management (e.g., Librela® for dogs).