14 – Small Animal NSAIDs Flashcards
1
Q
Small animal NSAIDs examples
A
- Carprofen (dogs)
- Meloxicam (cats+dogs)
- Coxibs
2
Q
Carprofen
A
- Considered ‘COX2 selective’
- Racemic mixtures (S+R enantiomers)
o S-enantiomer more potent - Oral chews and injectable
- *only DOGS
3
Q
Carprofen indications
A
- Osteoarthritis (chronic)
o *strong evidence - Post-op pain
4
Q
Carprofen adverse events
A
- Low, but variable incidence of vomiting and diarrhea
- Idiosyncratic (NOT dose-dependent) hepatic toxicity in dogs!
o Very rare (NOT HIGHER in LABS)
o Within few days/weeks of therapy
o Pre-treatment blood samples necessary to know (check liver enzymes)
5
Q
Meloxicam
A
- ‘COX-2 preferential’
- Oral suspension, tablets, infectable
- EBM analysis for arthritis=’high level of comfort’
6
Q
Oral suspension of meloxicam: dog vs. cat doses
A
- Dogs: 1.5mg/ml
- Cats: 0.5mg/ml
- *useful formulations=can come up with WHATEVER DOSE you want
- **can use the LOWEST EFFECTIVE DOSE and TITRATE your way down
7
Q
Meloxicam indications
A
- Acute AND CHRONIC musculoskeletal disorders (dogs)
- Acute musculoskeletal disorders (cats)
- Post-op pain (orthopedic, soft tissue surgery)
o Better than post-op butorphanol
8
Q
Meloxicam adverse events
A
- Dogs: typical
o Low incidence of vomiting and diarrhea (similar to carprofen) - USA: NO musculoskeletal claim in cats (‘black box warning’)
9
Q
Coxibs
A
- COX-2 selective
10
Q
Coxibs examples
A
- Deracoxib (tablets, dogs)
- Firocoxib (tablets, EQUINE as well)
- Robenacoxib (oral+injectable, dogs and cats)
11
Q
Coxibs indications
A
- Chronic osteoarthritis
- Orthopedic post-op pain (dogs)’
12
Q
Coxibs adverse events
A
- Low incidence of vomiting and diarrhea
- Renal tubular degeneration at high doses
- Cases of GI perforation at high doses
13
Q
Firocoxib dose between dogs and horses
A
- Dog dose is 50x more (5mg/kg dog vs. 0.1mg/kg horse)
o Both get a 57mg tablet!
14
Q
Robenacoxib (Onsior tablets) indications for cats
A
- Relief of ACUTE pain and inflammation with cat bites and scratches
- As an adjunctive medication in control of postoperative pain and inflammation
- *Control of pain and inflammation with CHRONIC MUSCULOSKELETAL disorders (only one that has chronic)
- *highly COX2 selective (maybe not great?)
15
Q
Robenacoxib (Onsior tablets) indications for dogs
A
- Control of pain and inflammation associated with OSTEOARTHRITIS
- As an adjunctive medication in control of POSTOPERATIVE pain and inflammation with soft tissue surgery
16
Q
‘old’ small animal NSAIDs
A
- Ketoprofen (only large animal now)
- Tolfenamic acid
- Phenylbutazone
- Dipyrone
- Vedaprofen
17
Q
What about human NAIDS to use in vet med?
A
- Not approved for vet med
- *toxicity
o Ibuprofen is a big one! (most cases do survive) - *’cheap alternative’ (NOT worth the RISK!)
18
Q
Safety and efficacy of human NSAIDs for small animals?
A
- Not nearly as good as approved vet drugs
- *smaller therapeutic window (increased effective dose and decreased toxic concentration)
19
Q
Small animal ‘not NSAIDs’ for osteoarthritis
A
- Galliprant (dogs)
- Solensia (cats)
- Liberla (dogs)
20
Q
Galliprant
A
- Recently approved for use in dogs with arthritis
- Oral tablet
- *PGE2 receptor antagonist (NOT a COX inhibitor)
o Blocks EP4 receptor
21
Q
Galliprant blocks EP4 receptor
A
- Involved in mediating pain and PGE2-elicted sensitization of sensory neurons
22
Q
Why use galliprant?
A
- Theory might be safer than NSAIDs?
o Since not blocking the production of PG, just the PG receptors - Data shows efficacy is likely worse!
- Concurrent use with NSAIDs not recommended
o Adverse events likely to occur - Ex. animal that already has GI problems or kidney issues
23
Q
Gallipratn adverse reactions
A
- *relatively low incidence=safer than NSAIDs
- Vomiting
- Diarrhea
- Anorexia
- Lethargy
- Buccal ulcer and IMHA (lower)
24
Q
Galliprant efficacy
A
- Not fantastic treatment success
- Slight difference between treatment and placebo
25
Q
Solensia
A
- Recently approved to use in cats with arthritis
- *monoclonal Ab specific for FELINE nerve growth factor (NGF)
- Not really a drug, technically a ‘biologic’
- Dose: 1-2mL/cat SC, repeated monthly
- *doesn’t fix the osteoarthritis
26
Q
Nerve growth factor (NGF)
A
- Upregulated during chronic inflammatory conditions (Ex. osteoarthritis)
- Involved in pain response
27
Q
Solensia pharmacokinetic(PK) highlights
A
- Long-acting injection
o Half-life of 10-12 days
o One injection per month
o Two injections to reach steady state - **doesn’t get broken down quickly
o Proteolysis (inactive peptides)
28
Q
o Proteolysis (inactive peptides)
Solensia efficacy and safety
A
- It works and seems safe
- Hard to do the studies in cats
- Not necessarily better than NSAIDs
29
Q
Librela (bedinvetmab)
A
- Approved for dogs with arthritis
o Monoclonal antibody specific for canine NERVE GROWTH FACTOR (NGF) - Safe (only 1% do dogs developed anti-drug antibodies
30
Q
Is it good idea to combine NSAIDs with ‘not-NSAIDs’ for multi-modal osteoarthritis analgesia?
A
- Don’t really know yet
- *benefits of multimodal analgesia is well documented
- BUT
o Efficacy may not be synergistic for theses types
o Choric use might be riskier than other analgesic regimes - ADVICE: be cautious, use LOWEST NSAID dose
31
Q
Pharmacovigilance (adverse event reporting): NSAID safety
A
- Increased reported AE does NOT mean less safe (need a denominator)
- Conditions of use vary between NSAIDs (one time vs. life-long)
- Voluntary reporting can be skewed
- Hard to find accurate data, objective comparisons are difficult
32
Q
Systematic review of NSAID safety in dogs
A
- High evidence for carprofen, firocoxib and meloxicam
- Less evidence for deracoxib, ketoprofen, robenacoxib (not necessarily less safe)
- Vomiting and diarrhea most common clinical signs
- Hepatic events more likely to be an idiosyncratic hepatoxicity (dose independent)
- Kidney and GI can be DOSE-dependent
33
Q
NSAIDs in cats and safety
A
- Decrease glucuronidation and hepatic clearance of NSAIDs=increase half-life
- *approved products: meloxicam and robenacoxib
- Firocoxib: minimal safety data
- Carprofen: highly variable half-life between cats
34
Q
Meloxicam adverse drug events in cats
A
- Renal failure caused by hypovolemia?
o No change in GFR in euvolemic, healthy cats!
o No change in GFR in euvolemic cats with azotemia
o *dehydrated cats (and other animals)=more at risk of renal injury - Idiosyncratic or other mechanisms
- Did NOT appear to reduce lifespan
- Relatively now
35
Q
Is it okay to use Meloxicam in cats with chronic renal failure?
A
- Make sure HYDRATED
- Progression of renal failure is NO worse than a control group
- Using a very small dose
- Some evidence: may slow down progression of kidney disease?
36
Q
Long term NSAID use in cats summary
A
- *can be done successfully
37
Q
What have we learned about NSAID use in small animals?
A
o GI lesions
o Other GI signs
o Hepatic and renal damage
- *no newer NSAIDs are consistently more effective than others
- *USE THE LOWEST EFFECTIVE DOSE!
