NSAIDs - pharmacology and relevance to clinical practice

Question 1

mechanism of effect

Answer 1

decrinflbyinhibitingproduction ofprostaglandinsreleasedbydamagedtissuethroughinhibitionofcyclo‐oxygenaseenzymes (COX)

Question 2

clinicalindications

Answer 2

Controlpain+ inflinnoninfectious/nonallergic infldisorders
decr plateletaggregation
Ophthalmology
Managementofsomeimmunologicaldiseases
managementofendotoxicshock

Question 3

in which diseases is a decr in plateletaggregation needed

Answer 3

Thromboembolus

Heartwormdisease

Question 4

use in ophthalmology

Answer 4

Rxofkeratitisandscleritis
donotinhibitre-epithelializationofthecornea
intraocularsurgery

Question 5

use in managementofsomeimmunologicaldiseases

Answer 5

SLEandrheumatoidarthritis
Anti‐infl
MaystimulateT‐suppressorcellsagainstT‐helpercells+auto‐antibody‐producingBcells

Question 6

COX‐1 - function

Answer 6

Produceprostaglandinsimportantinthephysiologicalmodulationoffunction

Question 7

COX‐2 - when is it activatedandreleased

Answer 7

tissuedamage
bacteriallipopolysaccharide
cytokines
growthfactors
inflwherePGE2ispredominanteicosanoid

Question 8

COX‐2 inhibition ‐ clinicalbenefits

Answer 8

suppression of infl, pain + fever

Question 9

COX‐2inhibition - cancers that can be treated

Answer 9

colon
pancreas
lung
transitionalcellcarcinoma
melanoma

Question 10

best Cyclo‐oxygenase‐assaymethod

Answer 10

whole blood assay

Question 11

Cyclo‐oxygenase‐assay - COX-1

Answer 11

Inhibitionofclot‐inducedthromboxaneB2 production

Question 12

Cyclo‐oxygenase‐assay - COX-2

Answer 12

Inhibitionoflipopolysaccharide(LPS) ‐ inducedprostaglandinE2 (PGE2)production

Question 13

COX‐1:COX‐2 ratio

Answer 13

Varieswithdifferentdrugs
differenttoxicityprofiles
OtherfactorsmayinfluencedegreeofsafetyofNSAIDs

Question 14

NonselectiveCOXinhibitors

Answer 14

Aspirin
Phenylbutazone
Ketoprofen
Tolfenamicacid

Question 15

PreferentialCOX‐2inhibitor

Answer 15

2to40‐foldmoreselectiveforCOX-2
Analgesic+anti‐inflactivityatdosesthatinhibitCOX‐2butnotCOX‐1
SomeCOX‐1inhibitionpossibleatelevated/therapeuticdosages

Question 16

PreferentialinhibitorsofCOX‐2

Answer 16

Meloxicam
Carprofen
Mavacoxib
Cimicoxib

Question 17

selectiveinhibitorsofCOX‐2

Answer 17

Firocoxib

Robenocoxib

Question 18

Dualinhibitor

Answer 18

Tepoxalin

Question 19

Speciesdifferences

Answer 19

Potency

RelativeselectiveforCOX‐1andCOX‐2

Question 20

Carprofen - dog

Answer 20

COX‐2preferential

Question 21

Carprofen - cat

Answer 21

Butsignificantlylongerhalflifethandog

Dailydosing= GIdisaster

Question 22

Carprofen - horse

Answer 22

non-selective

Question 23

pharmacokinetics

Answer 23

Wellabsorbedfromstomach+smallintestine
Wellabsorbedaftersubcutaneous/intramuscularinjection
Oromucosaldeliverycanachieveeffectivesystemiclevels
readilypenetrateinflammedtissue
Highlyproteinbound

Question 24

metabolism

Answer 24

excretedatvaryingrates-dependsonmetabolicpathway+
extentofenterohepaticcirculation
Eliminationhalf‐lifevariesconsiderablybetweendrugs+species
differs across species

Question 25

Potential adverse effects 

Answer 25

GI Renal Haematological

Question 26

PGE and PGI2 protect the gastric mucosa by...

Answer 26

inhibiting gastric acid secretion maintaining mucosal blood flow being involved in secretion + composition of healthy mucous intercellular messengers for the stimulus of mucosal cell turnover + migration

Question 27

main mechanism by which GI ulceration occurs

Answer 27

inhibition of COX-1

Question 28

gut cells expressing COX-2

Answer 28

macrophages neutrophils myofibroblasts endothelial cells

Question 29

Can COX‐2 inhibition retard ulcer healing? 

Answer 29

possibly

Question 30

COX-2 in the gut

Answer 30

rapidly expressed in response to GI injury and contributes significantly to mucosal defense and repair

Question 31

use of COX-2 inhibitors during infl

Answer 31

safety in presence of infl needs to be shown | shouldn't be used during infl

Question 32

Other factors that induce gastrointestinal damage

Answer 32

relative rate of gastric absorption  systemic availability of the drug via the circulation to the mucosa direct damage to gastric mucosa degree of enterohepatic re‐cycling

Question 33

Ulcerogenic potential increased by...

Answer 33

concurrent corticosteroids dehydration hypovolaemic shock disruption to normal gut blood flow

Question 34

Prostaglandins and renal function

Answer 34

When renal perfusion reduced, renal prostaglandins maintain renal blood flow via their vasodilatory actions 

Question 35

significant renal toxicity if...

Answer 35

volume‐depleted avidly retaining sodium  pre‐existing renal insufficiency

Question 36

Haematopoietic effects - Thromboxane

Answer 36

potent vasoconstrictor + activator of platelet aggregation | Inhibition of thromboxane can lead to incr risk of bleeding

Question 37

NSAIDs and the liver

Answer 37

NSAIDs undergo extensive hepatic metabolism | Care with hepatic disease