Lecture 6 & 7: NSAIDs 1 & NSAIDs 2- Specific NSAIDs used Clinically

What is the mechanism of action of NSAIDs?

Inhibit cyclooxygenase (COX) enzymes → block prostanoid synthesis

What are the three COX isoforms and their roles?

COX1: homeostasis; COX2: inflammation, pain, fever; COX3: central pyresis

What are the main clinical indications for NSAIDs?

Analgesia, antipyresis, anti-inflammatory, anti-endotoxicosis, anti-coagulation

Which types of pain are mitigated by NSAIDs?

Chronic pain, hyperalgesia, some visceral pain, partial relief of neuropathic pain and allodynia

How do NSAIDs alter nociception?

Increase nociceptor activation threshold by inhibiting PGE2

What are three homeostatic functions of COX1?

Gastroprotection, platelet aggregation, renal blood flow regulation

How do COX1 and COX2 differ in basal activity?

COX1 is constitutive; COX2 is inducible and upregulated during inflammation

Why is COX2 a better NSAID target than COX1?

COX2-selective inhibition reduces inflammation while sparing COX1-mediated homeostasis

How do NSAIDs reduce fever?

Block PGE2 in hypothalamus; COX3 may be involved centrally

How do NSAIDs alter inflammation?

Block PGE2-mediated vasodilation and synthesis of pro-inflammatory mediators

Why does LOX inhibition help minimize NSAID GI side effects?

Leukotrienes are gastrotoxic; LOX inhibition reduces their production

What are four major adverse effects of NSAIDs?

GI ulceration, hepatotoxicity, nephrotoxicity, cardiovascular imbalance

Which drugs should not be combined with NSAIDs?

Corticosteroids, anticoagulants, antihypertensives, aminoglycosides

Why are NSAIDs ineffective against rheumatoid arthritis?

RA involves COX-independent platelet microparticles that erode joints

Which NSAIDs are safest in cats?

Robenacoxib, meloxicam (single injection), low-dose aspirin

Which NSAIDs are COX2-selective and GI-sparing?

Deracoxib, firocoxib, robenacoxib, meloxicam

Which NSAID treats visceral pain?

Flunixin

Which NSAIDs are used against endotoxemia?

Flunixin and DMSO

Why prescribe carprofen in dogs and what is the risk?

Cheap COX2-selective NSAID; risk of hepatotoxicity, especially in Labradors

Which NSAIDs are banned in food animals?

Phenylbutazone and grapiprant

Why were some coxibs removed from the market and why is this not a problem in dogs?

Removed due to CV risk in humans; dogs rarely develop CV disease

Which coxibs are used in veterinary medicine?

Deracoxib, firocoxib, robenacoxib

Which NSAID is approved in swine?

Flunixin

Which NSAIDs are preferred in horses?

Phenylbutazone and flunixin

Why is acetaminophen a weak NSAID?

Does not inhibit peripheral COX2; acts centrally on COX2 and COX3

What is the administration advantage of meloxicam and robenacoxib?

Meloxicam: oral suspension; robenacoxib: oral and injectable, tissue-specific

What is unique about tepoxaline and its gastroprotective effect?

Inhibits COX1, COX2, and LOX; LOX inhibition reduces GI toxicity

What is the unique clinical use of piroxicam?

Adjunct for transitional cell carcinoma; combined with misoprostol and chemotherapy

Which NSAID is safest for long-term use in cats?

Robenacoxib

What limits long-term phenylbutazone use in horses?

Extended excretion; banned in food animals due to human toxicity

How does ketamine help treat endotoxicosis?

Subanesthetic doses block PG-mediated effects of LPS; synergistic with flunixin

Why does aspirin cause bleeding disorders?

Irreversibly inhibits COX1 in platelets → no thromboxane synthesis

Why are some NSAIDs contraindicated in pregnancy?

Inhibit PGF2α → delays parturition and affects implantation

What are DMSO precautions, uses, and combinations?

Wear gloves; used topically/IV; scavenges free radicals; can be combined with corticosteroids

Which NSAID group is best for long-term use in dogs?

Coxibs (e.g., deracoxib, firocoxib)

What are the pharmacokinetics of most NSAIDs?

Highly protein-bound, metabolized by liver, weak acids, subject to first-pass effect

Why are injectable NSAIDs tissue irritants?

They are acidic and poorly tolerated parenterally

Which NSAID is COX2-selective in horses and COX1-selective in dogs?

Flunixin

Which NSAID is preferred for equine colic and endotoxicosis?

Flunixin

Does flunixin bind LPS directly?

No — it blocks PG-mediated effects of LPS

What is the COX selectivity of acetaminophen?

Central COX2 and COX3 inhibition; no peripheral COX1 or COX2 inhibition

Why is acetaminophen hepatotoxic?

Forms toxic metabolites with chronic or high-dose use

Which NSAID group is most nephrotoxic?

Propionic acid derivatives (e.g., ibuprofen)

Which NSAID is COX2-selective and widely used in dogs?

Carprofen

What is a side effect of carprofen in dogs?

Reversible hepatotoxicity, especially in Labradors

Why is carprofen contraindicated in pregnancy?

Inhibits PGF2α → prolongs gestation

Which NSAID is used for PBZ-unresponsive myositis in horses?

Naproxen

What are two irreversible effects of aspirin?

Prolonged bleeding time and GI ulceration

Why does aspirin prolong bleeding time?

Irreversibly inhibits COX1 in platelets, which cannot regenerate

Why is aspirin contraindicated for long-term use in dogs?

Exacerbates osteoarthritis due to COX1 inhibition

Which NSAID is banned in lactating dairy cattle?

Phenylbutazone

Which oxicam is approved for cats?

Meloxicam (single injection only)

Which oxicam is used for bladder cancer in dogs?

Piroxicam

Which NSAID can be used instead of piroxicam for TCC?

Deracoxib (0.02 mg/kg)

Which coxib is approved for cats?

Robenacoxib (Onsior)

Which coxib has high Vd and is eliminated via bile?

Firocoxib

Which NSAID inhibits COX1, COX2, and LOX?

Etodolac

What is a side effect of etodolac?

Keratoconjunctivitis sicca (dry eye)

Which topical NSAID is used in horses?

Diclofenac

What is grapiprant and its mechanism?

PGE4 receptor antagonist (Galliprant); used for OA in dogs

What is a precaution when handling DMSO?

Wear gloves — absorbs through skin and causes garlic taste

What is tin-117m used for?

Intra-articular injection for elbow OA; provides relief for up to one year

Which NSAID is COX3-selective and approved in horses?

Dipyrone — used IV for pyrexia

What are anti-NGF antibodies used for?

Treating OA pain in dogs (bedinvetmab) and cats (frunevetmab)

What is the next-generation NSAID strategy?

Spare neutrophils to prevent transition from acute to chronic pain

What is the mechanism of MAGL inhibitors?

Increase 2-AG → inhibit pain-transducing neurons via endocannabinoid system