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