NSAIDs work by inhibiting the enzyme cyclooxygenase, which prevents the formation of prostaglandins involved in inflammation, pain, and fever. They are metabolized in the liver and their half-lives determine dosing regimens, with longer-acting NSAIDs increasing risks. NSAIDs should be avoided in patients with aspirin sensitivity or asthma, as they inhibit the same enzyme and can cause similar reactions. NSAIDs differ in their selectivity for the COX-1 and COX-2 enzymes, with non-selective NSAIDs inhibiting both and posing greater risks of gastrointestinal and platelet effects.

1. NSAID /Anti-Inflamation
Mechanismof action
The mechanismof actionof NSAIDscanbe dividedintotheireffectson inflammation,pain,andfever.
Anti-inflammatoryeffectNSAIDsexerttheiranti-inflammatoryeffectthroughinhibitionof prostaglandin
G/H synthase,orcyclooxygenase,whichisthe enzymecatalyzingthe transformationof arachidonicacid
to prostaglandinsandthromboxanes.Thisenzyme hastworecognizedforms:cox-1andcox-2.Selective
inhibitionof cox-2leadstodecreasedGIside effects.Recentworksuggeststhat activationof endothelial
cellsandexpressionof cell adhesionmoleculesplay arole intargetingcirculatingcellstoinflammatory
sites.NSAIDsmayinhibitexpressionof these cell adhesionmoleculesandmaydirectlyinhibitactivation
and functionof neutrophils.
Analgesiceffect
Althoughtheyare classifiedasmildanalgesics,NSAIDshave amore significanteffectonpainresulting
fromthe increasedperipheralsensitization thatoccursduringinflammationandleadsnociceptorsto
respondtostimulithatare normallypainless.Inparticular,itisbelievedthatinflammationleadstoa
loweringof the response thresholdof polymodalnociceptors .
Antipyreticeffect
NSAIDsexerttheirantipyreticeffectbyinhibitionof prostaglandinE2 (PGE2) synthesis,whichis
responsible fortriggeringthe hypothalamusto increase bodytemperature duringinflammation[3].
Pharmacokinetics
NSAIDSare metabolizedprimarilyinthe liver.Theyvaryintheirhalf-livesandbioavailability.Giventhe
multitude of available NSAIDs,the variabilityof theirhalf-livesallowsfordifferentdosingregimens.
Althoughdecreasedfrequencyof dosingimprovescomplianceasa general rule,considerationmustbe
giventothe increase inrenal dysfunctionassociatedwithlonger-actingNSAIDs.Ithasalsobeen
speculatedthatuse of dailydosedmedications,byimprovingcompliance,mayincrease the risk of GI
bleeding.Variabilityinsusceptibilitytoadverse effectsof various NSAIDsdoesnotseemtobe due to
difference inpharmacokinetics.Hepaticfunction,renalfunction,andage mustbe consideredbefore
prescribingand dosing.
Aspirin-inducedasthma
NSAIDsshouldbe avoidedinpatientswhohave establishedsensitivityto aspirin.Allpatientswhoare
newto NSAIDsshouldbe warnedaboutthis side effect.Itisseenmore commonlyinpatientswhohave
asthma,nasal polyps,andhistoryof rhinitis.The prevalence of aspirin-exacerbatedrespiratorytract
disease isabout10% inthe general populationandabout21% inadultswhendeterminedbyoral
provocationtesting.Itisassociatedwith rhinosinusitisandnasal polypsandpresentsmostoftenas
rhinitisand

2. asthma.Althoughpatientsare describedashavingaspirinsensitivityoraspirin-inducedasthma,theyare
at riskfor adverse reactionsfromany NSAIDthatinhibitscox-1.There isrecentevidence thatsuggests
that selectivecox-2inhibitorsare asafe alternative inthispopulation,butthisremainstobe confirmed
inlarge,well-controlledtrials .
Aspirinshouldbe usedwithcautioninpatientswhohave renal dysfunctionorbleedingdisordersandin
elderlypatients,inwhomevenbabyaspirin caninduce commonside effects.Additionally,inelderly
patients,tinnitusis commonlyseenastherapeuticlevelsare reached.Inpractice,aspirinisuncommonly
usedforthe managementof musculoskeletal painbecause the needforfrequentdosing,the
antiplateleteffect,andthe riskof GI bleeding, andotherissuesmake foranarrow therapeuticmargin.
Effectson platelets
AspirinandnonselectiveNSAIDsproduceinhibitionof plateletfunction viatheirinhibitionof COX1.In
the case of aspirin,the inhibitionisirreversible,sothe effectonplateletfunctioncontinuesforthe life of
the affected platelet(7–10days).In contrast,nonselectiveNSAIDscause areversible inhibitionof COX1,
so that the effectonplateletfunctioncorrespondstothe half-life of the specificdrug,usuallylasting
from2 to 12 hours[17].Because COX-2inhibitorshave little effectonCOX-1,theyare lesslikely than
nonselective NSAIDstoproduce clinicallysignificanteffectsonplatelet function.
Classificationofnon-steroidal analgesic
Group Analgesic
Salicylates Aspirin
Para-Aminophenol derivatives Paracetamol
Aceticacidderivatives Indomethacin
Sulindac
Etolac
Fernanates
Tolmetin
ketorolac
Propionicacidderivatives Ibuprofrn
Naproxen
Fenoprofen
Ketoprofen
Flubiprofen
oxaprozin
Enolicacid Piroxicam
Cox-2selective inhibitors Celoxib
valdecoxib

3. Antibiotics
The classificationtable: