NSAIDS Flashcards
Non-steroidal anti-inflammatory drugs that include:
Over the counter (OTC)
Prescription
Non-opiods
Clinical uses of NSAIDS
Musculoskeletal pain (OA, muscle, tendon/lig, fracture)
Visceral pain (abdominal and thoracic)
Pain pathway intervention
Anti-inflamm. agents, COX 2 inhibitor
COX 1(constitutive)
Housekeeping function: physiological stimuli
PGI2: renal function
TXA2: platelet function
PGE2: gastric protection
PGI2 (prostacyclin)
Localized in vasculature tissue
Potent vasodilator
Exerts antiaggregaotry activity on blood platelets
TXA2 (thomboxane)
Vasoconstrictor and proaggregate in thrombus formation
Dominates in platelets
PGE2
Direct vasodilator
Relaxes smooth muscle
Inhibits NE release
Suppresses T cell receptors signaling
Fever
COX2 (inducible)
Pathological condition: inflammatory stimuli
Inflammatory sites (macros) → Pro-inflammatory PGs and other inflammatory mediators → Inflammation
NSAIDs are more selective for __________
COX2
Screening test: COX ratio
IC50 (COX1) :IC50 (COX 2)
Compare potency of drug towards COX isofroms
<1 or close to 1 COX ratio
Less concentration to inhibit COX1
More concentration to inhibit COX2
Classic NSAID
> 1 COX ratio
Less concentration to inhibit COX2
More potent for COX2
Preferential or selective NSAID
Side effects of prolonged COX 2 inhibition
Disturb balance between p PGI2 andp TxA2
LEADING TO ↑ PLATELET AGGREGATION AND VASOCONSTRICTION
Classical NSAIDs
Aspirin
Flunixin meglumine
Phenylbutazone
Acetaminophen* (paracentamol)
What do classical NSAIDS do?
Inhibits COX 1 and COX2 equally leading to ↓ inflammatory response
Preferential NSAIDs
Inhibits COX2 more than COX1
Carprofen and meloxicam
COX2 selective (Coxib) NSAIDs
Inhibits COX2 wayyy more than COX1
Firocoxib, robenacoxib, deracoxib
EP4 Antagonist drugs
Grapiprant (galiprant)
NSAID adverse effects on the GI tract
Gastroduodenal ulcer, GI bleeding
Dogs > cats, horses (colitis)
Most common cause: OVERDOSING
Risk factors: geriatric patients, concurrent use of gluccos
Pathogenesis of COX inhibitors
Direct irritation (acid)
Inhibition of gastro protection
Prevention and treatment
Accurate dosing
Anti-ulcer drugs: H2 antagonists (famotidine), proton pump inhibitors (omeprazole), PGE analogue (misoprostol)
How do PGs affect the kidney?
Insure intramedullary renal blood flow
Urine formation
NSAID Renal adverse effects
Analgesic nephropathy
Doesn’t occur in healthy animals with free water
↓ GFR, water retention, hypertension
Patients at risk for renal adverse effects
↓ blood flow to kidneys
Geriatric patients
Concurrent use of nephrotoxic/ active drugs
Effects of Classical NSAIDS on normal blood vessels
Inhibits COX 1, COX2 andPGI2 →vasodilation and inhibiting platelet aggregation
Effects of classical NSAIDS on damaged BVs
Inhibits COX 1 and TxA2 → vasoconstriction and promotes platelet aggregation
Effects of aspirin on BVs (damage and normal)
Prolonged bleeding time (withhold aspirin before surgeries)
Effects of Coxib on BVs (damage and normal)
Enhance blood clot formation and induce cardiovascular disease (banned for humans)
Hemopoietic NSAID adverse events
Stop platelet aggregation and prolonged bleeding time
Bone marrow depression
Thromboembolic disease (COX2 selective NSAIDs)
What drug cannot be used in cats due to bone marrow depression?
Phenybutazone
NSAID effects on Reproduction
Prolonged gestation (inhibition of uterine PGF2 and PGE2)
Lysis of corpus luteum
Initiates uterine contractions
NSAID PK
Weak acids (stomach ulcers), oral absorption
Highly > 90% bound to albumin
Hepatic Metabolism
Enantiomers
Acetaminophen (parcetamol)
Inhibition of peroxidase (POX)
Centrally acting analgesic and anti-pyretic
Poor anti-inflammatory
Acetaminophen contraindications
CATS
Deficiency in glucuronyl trasnsferase → hepatic toxicity and methemoglobinemia
Acetaminophen toxicity treatment
Promote glutathione formation (N-acetylcysteine and SAMe)
Microsomal enzyme inhibitor (cimetidine)
Anti-oxidants (vitamin C and SAMe)
Aspirin
Salicylic acid
Hepatic conjugation with glucuronide and renal excretion
Adverse effects of aspirin
Irreversible inhibition of platelet activity
CS: depression, vomiting, electrolyte imbalances, hyperthermia, convulsions, death, cartilage damage
Flunixin meglumine
Nicotonic acid
Used for visceral pain (horse colic) and endotoxemia
Injectable, oral paste, granules
Flunixin meglumine in food animals
Approved for use in cows for pyrexia
Prohibited (veal calves and lactating dairy cattle)
Adverse effects of Flunixin meglumine
Mask surgical pain in equine patients
Gastric ulceration
Clostridial myositis from IM injection
Phenylbutazone
Pyrazolone (enolic acid)
Used for musculoskeletal pain in horses and cattle
Used in dogs, toxic in cats
Phenylbutazone disposition
Metabolized by liver, highly protein bound (may displace other drugs)
Excreted in urine (alkaline ↑ excretion)
Phenylbutazone adverse agents
Narrow TI
Gastrointestinal ulcerations
Low serum protein concentrations
Extravasation of IV product
Renal papillary necrosis
GI ulceration treatment
Proton pump inhibitors (omeprazole)
PGE replacement (misoprostol)
Carprofen
Proprionic acid
First COX2 preferential drug approved in use in animals
Treats OA, preoperative management of pain
Carprofen adverse effects
Safest of new NSAID
Hepatotoxicity
Renal tubular disease
Meloxicam
Oxicam
OA in dogs
Post operative pain in cats
Popular in zoo, exotic wildlife
Meloxicam in dogs and cats
Cats: single dose only, renal failure, death, black box warning
Dogs: GI perforation
Firocoxib
Canine chew and equine injectable and paste
Used for OA
Loading dose required
Deracoxib
First coxib approved for use in animals
For OA in dogs and operative pain
Robenacoxib
OA for dogs and cats and post-operative pain
Tissue selective - longer at the site of inflamm
Gapiprant (galliprant)
EP4 receptor antagonist located @ sensory nerve ending
Dogs to control pain and inflamm. (OA)
Nerve growth factor
Produced by inflammatory cells
Binds to sensory nerve ending (↑ pain signal rate, releases more cytokines and proliferation)
NGF Inhibitor
Reduces pain signals
Reduce production of inflammatory repsonse
Monoclonal Ab
Ex: Bedinbetmab (dogs), frunevetmab (cats)
Bendinvetmab (Librela in dogs)
Monthly SC injection for OA pain in dogs
Contraindication: hypersensitivity, dogs under 12m, lactating, breeding or pregnant animals
Frunevetmab (Solensia in cats)
Pain due to OA, monthly Sc injection
Contraindications: Under 12 m or under 2.5 kg, breeding, lactating or pregnant animals
Side effects of frunevetmab
Scabbing on head and neck, dermatitis and pruritus
Contraindications for NSAIDs
Acute renal and hepatic insufficiency
Dehydration
Hypotension
↓ circulating blood volume: CHF ascites, hemorrhage, shock
Bleeding disorders/ coagulapathies
GI ulceration
