Anti-inflammatory Drugs part 2

Part 2 – NSAIDs Overview

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) are essential medications in veterinary medicine, playing a significant role in the management of inflammation, pain, and fever in animals. They are commonly used to treat a variety of conditions ranging from musculoskeletal disorders to post-surgical pain.

Inflammation Pathway

• Phospholipids: Integral components of cell membranes that are crucial during tissue injury, acting as precursors to inflammatory mediators.

• Phospholipase Activation: Triggered by corticosteroids, phospholipase converts phospholipids into Arachidonic Acid. This reaction is critical as Arachidonic Acid is the substrate for further inflammatory mediator production.

• Metabolism of Arachidonic Acid: It is enzymatically metabolized by two key pathways:

  • Cyclooxygenase (COX) Pathway: Produces prostaglandins and thromboxanes which are involved in inflammatory responses.

  • Lipoxygenase (LOX) Pathway: Produces leukotrienes, which are important in mediating the inflammatory response, particularly in bronchoconstriction and mucosal inflammation.

Mechanism of Action of NSAIDs

Most NSAIDs operate primarily by inhibiting the actions of COX and/or LOX enzymes:

• COX-1: This enzyme produces gastroprotective prostaglandins (like PgE) that help maintain gastric mucosal integrity and promote renal blood flow.

• COX-2: This enzyme is induced during inflammation and produces prostaglandins that create the sensations associated with pain and fever.

NSAIDs play a pivotal role in preventing conditions like hyperalgesia (increased sensitivity to pain) and allodynia (pain from stimuli that do not usually provoke pain), thereby improving the quality of life for affected animals.

Classification of NSAIDs

NSAIDs can be categorized based on their selectivity:

• Non-selective NSAIDs: Inhibit both COX-1 and COX-2 enzymes.

  • Examples: Aspirin, Phenylbutazone, Flunixin Meglumine, Diclofenac, Ibuprofen, and Naproxen.

• Selective NSAIDs: Specifically inhibit COX-2 enzymes to minimize gastrointestinal side effects while providing anti-inflammatory effects.

  • Examples: Carprofen, Etodolac, Deracoxib, Meloxicam, Firocoxib, Robenacoxib.

Precautions and Side Effects

Classic Adverse Effects of NSAIDs:

• Gastric Ulceration: NSAIDs can lead to mucosal injury due to the inhibition of COX-1, resulting in reduced protective prostaglandin secretion.

• Renal Papillary Necrosis: This can occur due to reduced renal perfusion in dehydrated patients or those with existing renal impairment.

• Idiosyncratic Hepatotoxicity: Rare instances of liver toxicity may occur in certain individuals, unrelated to the dose or type of NSAID used.

Recommendations:

• Prefer COX-2 selective NSAIDs to preserve gastric mucus production, which helps to protect the gastric lining.

• Ensure adequate hydration is maintained in patients, especially those at risk of kidney damage.

General Uses of NSAIDs

• All NSAIDs function as anti-inflammatory, antipyretics, and analgesics. Their versatility makes them suitable for a wide range of veterinary applications.

Monitoring:

• Regularly check kidney and liver enzyme levels in patients on prolonged NSAID therapy, especially in geriatric animals or those with pre-existing conditions.

Tolerance Levels:

• Horses: Generally very tolerant to NSAIDs.

• Dogs: Variable tolerance levels can exist among breeds and individual animals.

• Cats: Often the least tolerant, making dosing and drug selection critical.

Non-selective NSAIDs Overview

1. Aspirin:

   • Derived from salicylic acid; utilized to decrease platelet aggregation which is crucial in surgical or trauma settings.

   • Caution is advised in cats due to their unique metabolic pathways, and it should be discontinued 1 week before scheduled surgeries due to bleeding risks.

2. Phenylbutazone (Bute):

   • Commonly employed for musculoskeletal inflammation in horses.

   • Not approved for use in food animals because of potential adverse effects, including bone marrow suppression and the risk of aplastic anemia.

3. Flunixin Meglumine (Banamine®):

   • Widely used in horses for treating colic and other musculoskeletal injuries, as well as possessing antipyretic properties.

   • Its use in dogs is discouraged due to the high risk of gastrointestinal toxicity.

Selective NSAIDs Detail

1. Carprofen (Rimadyl®):

   • A COX-2 inhibitor with less ulcerogenic potential; indicated for degenerative joint disease and postoperative pain in dogs.

2. Etodolac (EtoGesic®):

   • Typically prescribed for degenerative joint disease; monitoring required for keratoconjunctivitis sicca, a potential side effect.

3. Deracoxib (Deramaxx®):

   • Primarily prescribed for postoperative pain and osteoarthritis in dogs; comes in chewable tablet form for ease of administration.

4. Meloxicam (Metacam®):

   • Applicable in both dogs and cats; available as an oral suspension, typically administered once daily.

5. Firocoxib (Previcox®, Equioxx®):

   • Indicated for orthopedic surgeries and degenerative joint disease; formulations available for both dogs and horses, facilitating flexibility in treatment plans.

6. Robenacoxib (Onsior®):

   • Approved solely for cats in the US for short-term use addressing degenerative joint disease and postoperative pain management.

Other Anti-inflammatory Options

• DMSO (Dimethyl Sulfoxide): Acts as a solvent and has unique anti-inflammatory properties, inactivating superoxide radicals and approved for reducing swelling due to trauma. Notable side effects include skin irritation and a distinctive garlic taste upon absorption, so gloves are recommended during handling.

• Chondroprotectants: These agents are employed to prevent or reverse cartilage degeneration. This category includes substances such as:

  • PSGAG (Adequan)

  • Hyaluronic Acid (Legend)

  • Glucosamine & Chondroitin Sulfate (Cosequin), which support joint health and mobility in aging or injured animals.

Other Medications

• Acetaminophen (Tylenol®): Although not classified as an NSAID due to its lack of anti-inflammatory properties, it acts as an analgesic and antipyretic. Extreme caution should be taken in administering this drug to cats due to the serious risk of overdose and hepatic failure.

• Glucocorticoids vs. NSAIDs: Glucocorticoids tend to result in fewer adverse effects compared to NSAIDs but are not as effective for certain inflammatory processes. Combination therapy of glucocorticoids and NSAIDs is strongly discouraged due to the heightened risk of gastrointestinal complications and other adverse effects.