Unit 1.3 - Other Anti-Inflam Drugs

Frunevetmab injection - MOA

Monoclonal Antibody (mAb) Therapy

• Targets/blocks Nerve Growth Factor (NGF)

• NGF activates pain signals by ↑ the release of additional pain & inflammatory mediators

Frunevetmab Inj - Use & Forms

Use

• osteoarthritis pain in cats only

Forms

• Solensia

Frunevetmab Inj - side effects

• v+ and pain at injection site

• minimal liver and kidney involvement

Dimethyl sulfoxide (DMSO)

• is NOT an anti-prostaglandin or anti-COX drug

• anti-inflammatory mechanisms not totally understood

  • inactivates or traps destructive free radicals (superoxide and hydroxyl radicals) and thereby decreases tissue destruction

• Used as injectable and topically applied drug in horses; also in some otic preps — many extra label uses

• Penetrates skin - can dissolve and carry drugs or toxins into body if applied topically (clean skin before)

Chondroprotective agents

• “chondro” = cartilage

• some are regulated drugs, other are less regulated nutraceuticals

• Includes:

  • Polysuflated glycosaminoglycans (PSGAGs)

  • Hyaluronic acid or hyaluronate sodium

  • Glucosamine and chondroitin sulfate

Polysulfated glycosaminoglycans PSGAGs (Adequan®)

• Mimic the large and complex molecules of normal joint cartilage

• benefit is largely due to PSGAGs

  • stimulating new chondrocyte generation

  • new cartilage matrix by the new chondroyctes (cartilage cells)

  • inhibition of enzymes in the joint fluid that would degrade cartilage

Hyaluronic acid (HA) & Hyaluronate sodium

• chondro-protective agent that is an essential component of the normal synovial (joint) fluid

• increases the viscosity of the joint fluid

  • HA acts as a lubricant in the joint

• also scavenges free radical in the joint (like DMSO)

• some products are injected directly into the joint, others are systemically administered

Glucosamine & Chondroitin Sulfate

• Chondro-protective agent that is orally administered

  • OTC products sold as a nutraceutical

  • nutraceuticals are used like drugs but are actually food supplements

  • are regulated by FDA for safety as food supplements

• can be variable in the amount of active ingredients

Glucosamine & Chondroitin Sulfate: MOA

These drugs are precursors for PGAGs

• stims chondrocyte repair of cartilage

• stims production of hyaluronic acid

• inhibits destructive enzymes found in injured joints or cartilage

Glucosamine & Chondroitin Sulfate: Use

slowing onset/progression of osteoarthritis (OA)

Ibuprofen & Naproxen

• because there is a high incidence of GI effects (gastric bleeding, ulcers, death) and there are safer approved NSAIDs » don’t use these in dogs

• only use approved veterinary NSAIDs in large animal/equine

Acetaminophen

• is NOT an NSAID like other drugs

• analgesia is via inhibition of a COX-1 enzyme found only in the CNS (not in peripheral tissue)

• is also an antipyretic (anti-fever) » probably same mechanism

• because it doesn’t block peripheral COX 1, it does NOT cause stomach upset, GI ulcers or platelet bleeding

• limited use in vet med

• problem is TOXICITY IN CATS

Acetaminophen toxicity

• due to metabolism of drug to 2 non-toxic metabolites and one toxic metabolite

• toxic metabolite (NAPQI) occurs in all species but is usually quickly metabolized to a non-toxic metabolite by conjugation with glutathione

• cats do not metabolize very well by conjugation with glutathione » toxic metabolite created cannot be readily broken down to the non-toxic metabolite and accumulates

• toxic metabolite is very reactive with RBCs and liver cells » results in methemoglobinemia

• dogs are more resistant but can overwhelm normal metabolism resulting in liver signs such as jaundice

• Treatment: acetylcysteine (Mucomyst) - provides sulfhydryl group for converting toxic metabolite to non-toxic metabolite

which anti-inflammaotry is extremely toxic/deadly to cats?

acetaminophen