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4th year POS > NSAIDs - pharmacology and relevance to clinical practice > Flashcards

NSAIDs - pharmacology and relevance to clinical practice Flashcards

1
Q

mechanism of effect

A

decrinflbyinhibitingproduction ofprostaglandinsreleasedbydamagedtissuethroughinhibitionofcyclo‐oxygenaseenzymes (COX)

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2
Q

clinicalindications

A

Controlpain+ inflinnoninfectious/nonallergic infldisorders
decr plateletaggregation
Ophthalmology
Managementofsomeimmunologicaldiseases
managementofendotoxicshock

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3
Q

in which diseases is a decr in plateletaggregation needed

A

Thromboembolus

Heartwormdisease

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4
Q

use in ophthalmology

A

Rxofkeratitisandscleritis
donotinhibitre-epithelializationofthecornea
intraocularsurgery

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5
Q

use in managementofsomeimmunologicaldiseases

A

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

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6
Q

COX‐1 - function

A

Produceprostaglandinsimportantinthephysiologicalmodulationoffunction

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7
Q

COX‐2 - when is it activatedandreleased

A 
tissuedamage
bacteriallipopolysaccharide
cytokines
growthfactors
inflwherePGE2ispredominanteicosanoid
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8
Q

COX‐2 inhibition ‐ clinicalbenefits

A

suppression of infl, pain + fever

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9
Q

COX‐2inhibition - cancers that can be treated

A 
colon
pancreas
lung
transitionalcellcarcinoma
melanoma
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10
Q

best Cyclo‐oxygenase‐assaymethod

A

whole blood assay

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11
Q

Cyclo‐oxygenase‐assay - COX-1

A

Inhibitionofclot‐inducedthromboxaneB2 production

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12
Q

Cyclo‐oxygenase‐assay - COX-2

A

Inhibitionoflipopolysaccharide(LPS) ‐ inducedprostaglandinE2 (PGE2)production

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13
Q

COX‐1:COX‐2 ratio

A

Varieswithdifferentdrugs
differenttoxicityprofiles
OtherfactorsmayinfluencedegreeofsafetyofNSAIDs

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14
Q

NonselectiveCOXinhibitors

A

Aspirin
Phenylbutazone
Ketoprofen
Tolfenamicacid

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15
Q

PreferentialCOX‐2inhibitor

A

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

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16
Q

PreferentialinhibitorsofCOX‐2

A

Meloxicam
Carprofen
Mavacoxib
Cimicoxib

17
Q

selectiveinhibitorsofCOX‐2

A

Firocoxib

Robenocoxib

18
Q

Dualinhibitor

A

Tepoxalin

19
Q

Speciesdifferences

A

Potency

RelativeselectiveforCOX‐1andCOX‐2

20
Q

Carprofen - dog

A

COX‐2preferential

21
Q

Carprofen - cat

A

Butsignificantlylongerhalflifethandog

Dailydosing= GIdisaster

22
Q

Carprofen - horse

A

non-selective

23
Q

pharmacokinetics

A

Wellabsorbedfromstomach+smallintestine
Wellabsorbedaftersubcutaneous/intramuscularinjection
Oromucosaldeliverycanachieveeffectivesystemiclevels
readilypenetrateinflammedtissue
Highlyproteinbound

24
Q

metabolism

A

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

25
Q

Potentialadverseeffects

A

GI
Renal
Haematological

26
Q

PGEandPGI2 protectthegastricmucosaby…

A

inhibitinggastricacidsecretion
maintainingmucosalbloodflow
beinginvolvedinsecretion+compositionofhealthymucous
intercellularmessengersforthestimulusofmucosalcellturnover+migration

27
Q

mainmechanismbywhichGIulcerationoccurs

A

inhibition of COX-1

28
Q

gut cells expressing COX-2

A

macrophages
neutrophils
myofibroblasts
endothelial cells

29
Q

CanCOX‐2inhibitionretardulcerhealing?

A

possibly

30
Q

COX-2 in the gut

A

rapidlyexpressedinresponsetoGIinjuryandcontributessignificantlytomucosaldefenseandrepair

31
Q

use of COX-2 inhibitors during infl

A

safety in presence of infl needs to be shown

shouldn’t be used during infl

32
Q

Otherfactorsthatinducegastrointestinaldamage

A

relativerateofgastricabsorption
systemicavailabilityofthedrugviathecirculationtothemucosa
directdamagetogastricmucosa
degreeofenterohepaticre‐cycling

33
Q

Ulcerogenicpotentialincreasedby…

A

concurrentcorticosteroids
dehydration
hypovolaemicshock
disruptiontonormalgutbloodflow

34
Q

Prostaglandinsandrenalfunction

A

Whenrenalperfusionreduced,renalprostaglandinsmaintainrenalbloodflowviatheirvasodilatoryactions

35
Q

significant renal toxicity if…

A

volume‐depleted
avidlyretainingsodium
pre‐existingrenalinsufficiency

36
Q

Haematopoieticeffects - Thromboxane

A

potentvasoconstrictor+ activatorofplateletaggregation

Inhibitionofthromboxanecanleadtoincr riskofbleeding

37
Q

NSAIDsandtheliver

A

NSAIDsundergoextensivehepaticmetabolism

Carewithhepaticdisease

4th year POS (4 decks)

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