In-depth Notes on Anti-Inflammatory and Pain-Reducing Drugs

Inflammation

• Definition: Body's protective response involving cytologic and chemical reactions.
• Key Features:
  • Heat: Due to blood accumulation.
  • Redness: Resulting from vasodilation and blood congestion.
  • Swelling: Caused by increased capillary permeability leading to plasma leakage.
  • Pain: Triggered by swelling and the release of chemical mediators.
  • Loss of Function: Affected due to the above factors.

Chemical Mediators of Inflammation

• Prostaglandins: Promote vasodilation and pain.
• Histamines: Released from mast cells, leading to increased capillary permeability and smooth muscle contraction.
• Kinins: Contribute to pain and inflammation effects.

Types of Anti-Inflammatory Drugs

• Steroidal (Corticosteroids/Glucocorticoids):
  • Block phospholipase activity.
• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs):
  • Inhibit cyclooxygenase (COX) enzymes.
• Antihistamines:
  • Compete with histamine for H1 receptors.

Steroidal Anti-Inflammatory Drugs

• Corticosteroids:
  • Naturally produced by the adrenal cortex.
  • Types:
  • Glucocorticoids: Regulate metabolism & immune response.
  • Mineralocorticoids: Regulate electrolyte and water balance.
  • Effects:
  • Both mineralocorticoid and glucocorticoid effects seen in prednisone/prednisolone.
  • Can be classified based on duration of action:
    • Short Acting (< 12 hours)
    • Intermediate Acting (12 - 36 hours)
    • Long Acting (> 48 hours)
  • Administration Forms:
  • Injectables (SQ, IM, IV)
  • Oral formulations
  • Topical formulations

Adverse Effects of Glucocorticoids

• Common:
  • Polyphagia (+ weight gain), increased urination and thirst (PUPD).
  • Panting in dogs.
  • Behavioral changes, skin/coat changes, muscle wasting.
• Severe:
  • Delayed wound healing, increased infection risk, GI ulceration.
  • Iatrogenic hyperadrenocorticism (Cushing's syndrome).

Indications for Glucocorticoids

• Used in:
  • Treating inflammation, autoimmune disorders, allergic reactions, Addison’s disease, some neoplasms (e.g., lymphoma), ketosis in cattle.

Other Considerations for Glucocorticoid Use

• Prednisone is converted to active prednisolone in the liver; use prednisolone with cats or those with liver dysfunction.
• Horses poorly absorb prednisone orally; prefer topical.
• Avoid long-term systemic use and taper the drug upon discontinuation.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Function: Inhibit COX enzymes (1 and 2) resulting in anti-inflammatory, analgesic, and antipyretic effects.
• Key Properties:
  • Metabolized in the liver; potential for hepatic toxicity; high protein binding.
  • Adverse effects: GI issues (vomiting, diarrhea, bleeding), nephrotoxicity.

Classes of NSAIDs

• Salicylates: Aspirin; non-selective; poorly metabolized by cats.
• Pyrazalone derivatives: Phenylbutazone; used mainly in equine medicine; non-selective.
• Propionic acid derivatives:
  • Examples: Ibuprofen, ketoprofen, carprofen (dogs); preferentially inhibits COX-2.
• COX-2 selective NSAIDs:
  • Examples: Deracoxib, firocoxib, robenacoxib, meloxicam.
  • Note for cats due to safety concerns.

Antihistamines

• Block histamine's effects: vasodilation, increased permeability, smooth muscle spasms.
• Indications include pruritus, motion sickness, allergies.

Other Anti-Inflammatory Modulators

• DMSO: Potentially inactivates free radicals, penetrates the skin well.
• Immunomodulators: Can enhance or suppress immune response.
  • Examples: Cyclosporine (Atopica®), Oclacitinib (Apoquel®), Tacrolimus.