NSAID 2 Flashcards
What drugs are in the classical/traditional group
Acetaminophen, aspirin, flunixin meglumine, phenylbutazone
Drugs in the preferential group
Carprofen and meloxicam
Drugs in the COX II selective category
Firocoxib, robenacoxib, deracoxib
A type of EP4 antagonist
Grapiprant
NSAIDs absorption
- good oral absorption
- weak acids
NSAID Distribution
- at least 90% bound to albumin
- small Vd
- accumulation @ site of distribution
NSAID Hepatic metabolism
- hepatic metabolism= primary mode of clearance
- phase 1&2
- enterohepatic circulation
Acetaminophen
- peroxidase inhibition
- centrally acting analgesic and anti-pyretic
Feline acetaminophen toxicity
- contraindication for cats
- issue w/ phase 2 metabolism (deficiency in glucuronyl transferase)
- glutathione overwhelmed (hepatic toxicity and methemoglobinemia)
- single adult dose can be lethal
Treatment for acetaminophen toxicity
Promote glutathione formation, microsomal enzyme inhibitors, antioxidants
What promotes glutathione formation
N-acetylcysteine and S-adeosyl methionine
Cimetidine is a type of
Microsomal enzyme inhibitor
Disposition of aspirin
- variable bioavailability
- 50-70% protein bound
- rapid distribution into ECF (synovial, peritoneal, saliva, and milk)
- elimination via hepatic conjugation with glucuronide
- renal excretion
Adverse events of aspirin
- antithrombotic (inhibits platelet activity)
- wide safety margin in most species
Aspirin adverse events in cats
- requires glucuronidation for elimination
Clinical signs of aspirin toxicosis
Depression, vomiting, electrolyte imbalances, hyperthermia, convulsions, death
Chronic signs of aspirin toxicosis
Bone marrow depression, toxic hepatitis, GI bleeding, cartilage damage, and renal failure
Treatment for aspirin adverse events
Supportive care
Flunixin meglumine
- a nicotinic acid
- used for visceral pain (colic in horses)
- 80% bioavailability
- short 1/2 life
- long duration of effect due to irreversible COX inhibition
Flunixin meglumine is approved for use in
Cows for pyrexia
Flunixin meglumine is prohibited in
Veal calves and lactating dairy cattle
Adverse effects of flunixin meglumine
- mask surgical pain in equine patients
- gastric ulceration
- clostridial myositis from IM injection
Structure activity relationship of phenylbutazone
- pyrazolone (enolic acid)
- dosing forms (IV, granular, bolus, paste, tablet)
Uses of phenylbutazone in horses/cattle and dogs
- horses/cattle: musculoskeletal pain
- documented use in K9
In which species is phenylbutazone toxic
Cats
(Causes aplastic anemia & bone marrow depression)
Disposition of phenylbutazone
- metabolized by liver
- highly protein bound
- excreted in urine (more alkaline urine increases excretion)
Adverse effects of phenylbutazone
- narrow therapeutic index
(Use high end dose for short pd. Duration)
- GI ulceration
- low serum protein conc.
- extravasation of IV product (cervical tissue necrosis)
- renal papillary necrosis (if given wrong)
What do you treat gastric ulcers w/?
- proton pump inhib. (Omeprazole)
- PGE replacement (misoprostol)
- supportive care (IV fluids, correct acid/base disturb. & electrolyte abnorm.)
What happens if Cox1:Cox2 <1?
- less drug to inhibit COX1
(More COX 1. Activity)
What happens if COX1:COX2>1
- More drug to inhibit COX1
OR
- More potent for COX2
COX1 selective ratio drugs (ratio<1)
Aspirin, ketoprofen, phenylbutazole, flunixin, piroxicam, ibuprofen, naproxen
COX2 preferential (ratio>1-100:1)
Carprofen, etodolac, meloxicam
COX2 Selective (ratio>100-1000:1)
Firocoxib, robenacoxib, deracoxib
Carprofen forms
- injection, tablets, chews
Carprofen is a
Proprionic acid
Why should you be cautious w/ giving K9s carprofen chews?
Dogs think they’re treats, so if they gain access to the container, its easy for them to OD
Uses of carprofen
- 1st COX2 preferential drug approved for use in animals
- in animals: >6 wks, K9s being treated form OA, post-op pain mgmt
Why would carprofen be used in K9 puppies >6 wks old
- parvo
- trauma (pediatric spays & neuters)
Adverse effects of carprofen
- one of the safer NSAIDS
- gastric ulceration
- hepatotoxicity
- renal tubular disease
Hepatotoxicity caused by carprofen
- common in old patients
- seen w/ concurrent use of phenobarb.
- need to monitor carefully (liver enzymes & funct)
Forms of meloxicam
Tablet, oral susp., inj.
Therapeutic use of meloxicam
- OA in K9
- Cats post-op pain
Adverse events in cats using meloxicam
- single dose only
- renal failure
- death
- black box warning
Adverse effects of dogs using meloxicam
GI perforation
List COX 2 Selective drugs
Drugs that end in “-coxib”
EP4 agonist of interest
Grapiprant
Dose form of firocoxib
- K9 Chew
- equine inject. & paste
Disposition of firocoxib
- variable elim. 1/2 life
- K9: 9 hours
- equine: 48 hrs (loading dose needed)
Dose form of deracoxib
- chewable tabs
What was the first coxib approved for animal use?
Deracoxib
Deracoxib is used for
Post op pain and OA >4 mos
Dosage form of robenacoxib
Tabs & inj
Use of robenacoxib
- SID
- OA & post op pain
Disposition of robenacoxib
- short 1/2 life
- persists longer at site of inflamm
- long DOA
Indication of grapiprant
Control pain & inflamm assc. W/ OA in K9
EP4 Receptor
- PGE2 ligand
- @ sensory nerve end
- EP4 receptor antagonist
- K9 approved use
Nerve growth factor
- prod. By inflamm. Cells
- binds to sensory nerve ending, incr. pain signal rate
- releases more inflamm. Cytokines
NGF (nerve growth factor) inhibitor
- reduce pain signals
- reduce inflamm. Response prod.
- monoclonal antibody (bedinvetmab in K9; frunvetmab in cats)
Bedinvetmab
- K9 only
- monoclonal antibody that blocks NGF
- QM SQ inj. for osteoarthritis
- onset: 7-28 days; peak: 56 days
- no response after 2 Tx, then choose another Tx
- contraind.: hypersens., <12 mos age, breeding, pregnant, lactating, NGF inhibition messes w/ normal nervous system dev.
- t1/2: 12 days
Frunevetmab (Solensia)
- same MOA as bedinvetmab
- OA in cats
- QM SQ inj.
- t1/2: 10 days
- contraind.: <12 mos old, under 2.5 kg, breeding, lactating, pregnant
- AE: Scabbing on head and neck, dermatitis, pruritus
Common K9 NSAIDs
- carprofen (>6 wks)
- deracoxib (>4 m)
- meloxicam (>6 m)
- firocoxib (>6m)
Common cat NSAIDs
- robenacoxib (>4.5m; >5 lb)
- meloxicam (>6m; black box warning)
