Anti-inflammatory & Pain-Reducing Drugs

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

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.

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).

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.

DMSO:
- Mechanism unclear; used topically, reduces swelling, potential skin irritation, increases absorption of other drugs.
Immunomodulators:
- Modify immune response; examples include Cyclosporine, Tacrolimus, Oclacitinib.

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).