Nonsteroidal Anti-inflammatory Drugs Flashcards
NSAIDS
Commonly prescribed
Diverse class
Cox inhibitory
- analgesics
- anti inflame
- antipyretic
Approved NSAIDS for dogs
Carprofen
Etodolac
Meloxicam
Deracoxib
Firocoxib
NSAIDs approved for cats
Meloxicam
Robenacoxib
Approved nsaids in horses
Phenylbutazone
Flunixin
Firocoxib
Ketoprofen
Approved nsaids in bovine
Flunixin
Ketoprofen
Effects of prostanoids
Inflammation
-vasodilation
- ^ vascular permeability
- pain
Effects of prostanoids
Homeostasis
GIT protection
Renal perfusion
Platelet aggreagation
Bone formation & healing
Temp regulation
COX1
Constitutive enzyme
Normal physiological function
COX2
Inducible enzyme
Synthesized by macrophages
Induced by cytokines and inflammatory mediators
=inflame and pain
Cox 1 vs cox 2 inhibition
Drugs are categorized based on cox 2 selectivity
nonselective cox inhibitors
Phenylbutazone
Flunixin
Aspirin
Cox 2 preferential drugs
Meloxicam
Carprofen
COX2 selective drugs
Deracoxib
Robenacoxib
Firocoxib
COX1 selective
Aspirin
Cox 2 in homeostatic functions
Gastric and duodenal Musca
Cox 2 up-regulated in response to inflame
Protective and healing role
Kidney
- cox 2 upregulate in response to renal stress
- important in normal renal function
Potential MOAs
Some nsaids may inhibit nuclear factor Kappa-B
Some may inhibit kinase ERK
Physical distribution of cell signaling and protein to protein interactions
Interactions w endo opioid systems
PK for cox inhibitors
Oral absorption is high - feeding may effect
High protein bound
Biotransmored by hepatic mechanisms
Clearance varies - plasma vs inflamed tissue
Nonlinear kinetics
Examples of drugs impacted by admin w eating
Phenylbutazones absoption is delayed
Robenacoxib absorption is inhibited
Grapiprant absorption is increased
GI side effects
Common in dogs and horses
Nausea, vomiting, diarrhea, inappetence, pain
Diffuse directly into GI mucosa cells = damage
(Indirect mucosal injury) Decreased mucus secretion, diminished blood flow, inhibition of mucosal cell turnover & repair
Prognosis for GI side effects
Gastritis, enteritits, erosion, ulcers, perforation
Guarded
Typically attributed to super therapeutic doses
Concurrent corticosteroid admin
Concurrent GI disease or Injury
Dehydration
Tolerance - develops
Renal side effects
Primarily in horses (people)
Decreased renal perfusion, sodiu, and fluid retention
Supra therapeutic dose
Concurrent w corticosteroids admin
Concurrent dehydration, anesthesia, shock
Pre-existing renal disease
Hepatic side effects
Intrinsic
Acetaminophen and aspirin
Dose dependent and reproducible
Idiosyncratic
Any NSAID, carprofen, not dose dependent
Coagulation
Inhibition of COX1 decreases TXA2 & platelet function
Perioperative bleeding
COX1 sparing/cox2 inhibitor drugs have less likely to cause
Inhibition of COX1 decreases TXA2 & platelet function
Acetylated NSAID irreversibly inhibited platelets (7-10d)
Non-acetylated NSAIDS reversibly inhibit platelets
COX1 sparing/cox2 inhibitor drugs have less likely to cause
Increased risk of cardio events with COX2 selective drugs
Thromboemboli
(People problem)
Injection site reaction
Common in horses
Swelling, abscess, clostridial myositits, tissue necrosis
Phenylbutazone
Fluxinin meglumine
Minimizing adverse effects
Dosing appropriately
Ideal drug & formulation
PGE analog (GI protection)
Proton pump inhibitors
Avoid co administration w nephrotoxic drugs
Avoid co administration w NSAIDS or GC
Underlying diseases to show extreme caution when dosing
Sub clin renal disease, GI disease, liver disease
Anorexia, dehydration
Acetylsalicylic acid
Nonselective cox 1 selective
Oral
Antithrombotic (lung, laminitis, glaucoma)
OA or musculoskeletal pain
Irreversibly inhibits platelet aggregation (bleeding)
Narrow therapeutic index
Chondrocyte destruction
GIT bleeding/ulceration
What drug should you not give IM to horses?
Flunixin
Can cause major myonecrosis from IM injection
Flunixin meglumine Formulation, species, side effects
Oral - horses
Parenteral - horses, rum, pigs
Transdermal - rum
Treats orthopedic or soft tissue pain, visceral pain, endotox, pyrexia
Phenylbutazone Formulation, species, side effects
Nonselective
Oral - horses
Parenteral - horses
Orthopedic or soft tissue pain
Tissue necrosis w peri vascular injection
Narrow therapeutic index
Highest risk of GI tox
Ketoprofen
Parenteral - horses, rum
Muscle pain, pyrexia w BRD
Least ulcerogenic in foals
Carprofen
Formulation, species, side effects
Cox 2 preferential
Oral & inject - dogs
Ortho/soft tissue pain, OA, pain/inflammation
Anti-thromboxane activity
Idiosyncratic hepatic toxicosis
Meloxicam
Formulation, species, side effects
Cox 2 preferential
Oral, transmucosal - dogs
Parenteral - cats & dogs
OA, muscle pain/inflame, ortho/soft tissue surgery
Deracoxib Formulation, species, side effects
Cox 2 selective
Oral - dogs
Post op pain, OA pain, synovitis
GIT perforation, ^ coagulability
Never co admin w GC or NSAIDS
Firocoxib Formulation, species, side effects
Cox 2 selective
Tablets - dogs & horses
Paste, parenteral - horses
OA, synovitis, soft tissue pain/inflame
Takes long time to act (day 15)
Robenacoxib Formulation, species, side effects
Cox 2 selective
Oral, parenteral - cats & dogs
OA, muscle pain, othro/soft tissue surgery
Superior to Meloxicam
Non toxic in cats
Drugs that are COX 2 selective
Robenacoxib
Firocoxib
Deracoxib
Drugs that are cox 2 preferential
Meloxicam
Carprofen
Nonselective drugs
Phenylbutazone
Flunixin meglumine
Acetylsalicylic acid (aspirin)
