NSAID

2. Non steroid anti inflammatory
drug
Shereen Abdelsalam Elwan
Lecturer of Rheumatology and Rehabilitation
Tanta university

3. NSAID
O Weak organic acids bind to serum proteins so accumulate
at site of inflammation (inflamed joint often have a lower
PH than clinically uninvolved joints)

4. NSAID
NSAID Effect:
O Analgesic
O Antipyretic
O Anti inflammatory
O Anti platelet

5. NSAID
O work by inhibiting the activity of cyclooxygenase enzymes (COX-1
or COX-2). In cells, these enzymes are involved in the synthesis of key
biological mediators, namely prostaglandins, which are involved in
inflammation, and thromboxanes, which are involved in blood clotting
O . Corticosteriod inhibit the release of arachidonic acid metabolites,
namely prostaglandins (PGs) and leukotrienes,, via the induction of a
phospholipase A2 inhibitory protein, called lipocortin.

9. NSAID
Mechanism of action :
Inhibition of cyclooxygenase cause decrease in
prostaglandin production (Cox1 and Cox2)
Inhibition of lipoxygenase
Inhibition of superoxide formation
Inhibition of neutrophil aggregation

10. NSAID
 Inhibition of degenertive enzyme
 Inhibition of cytokine production by inhibition of NF,Kb
 Suppression of proteoglycan degredation in cartilage

11. NSAID
 carboxylic acid
 Salicylates​ : Acetylated : Aspirin Non acetylated : sodium
salicylate ,Diflunisal,Salsalate (Disalcid)
 Propionic acid : Ibuprofen, Naproxen,Fenoprofen,Ketoprofen
 Acetic acid : indole : indomethcin phenyl acetic acid : diclofenac
Enolic acid (oxicam),Piroxicam,Meloxicam
Cox2 inhibitor celecoxib ,etoricoxib

12. NSAID
 COX1 Specific (COX1 selective): low dose aspirin
 Cox non specific ( cox non selective): Ibuprofen,
indomethcin , naproxen
 Cox2 perferential (cox2 selective ) : meloxicam,
diclofenac
 Cox2 specific (cox2 highly selective): celecoxib

13. NSAID
O Most NSAIDs are non-selective and inhibit the activity of both
COX-1 and COX-2. These NSAIDs, while reducing
inflammation, also inhibit platelet aggregation (especially
aspirin) and increase the risk of gastrointestinal ulcers/bleeds.
O COX-2 selective inhibitors have less gastrointestinal side
effects but promote thrombosis and substantially increase the
risk of heart attack.

14. NSAID

15. NSAID
 Gastrointestinal side effect:
 Dyspepsia
 Gastro osophageal reflux
 Gastrodudenal ulcer
 GIT hemorrhage
 Diarrhea
 Small bowel webs

16. NSAID
 Prostaglandin
 Induce protective superfacial mucosus barrier
 Induce bicarbonate output
 Increase mucosal blood flow in the superfacial gastric cell layer
 Inhibit gastric acid synthesis

17. NSAID
 Risk for NSAID induced gastroduodenal ulcer:
 Old age
 History of peptic ulcer disease
 Higher dose, prolonged use of NSAID
 Chronic disease
 Concomitant corticosteriod, warfarin ,low dose aspirin
 Suspected risk factor tobacco, alcohol,infection with
helicobacter pylori

18. NSAID
 Nephrotoxic side effect :
 Vasoconstriction leading to decrease glomular filteration rate and
increase creatinine
 Increase sodium retention and blood volume
 Pupillary necrosis
 Hyperkalemia
 Hyponatremia
 Interstital nephritis

19. NSAID
 Prostaglandin is vasodilator for renal arteries
 Increase renin release
 Increase sodium loss

20. NSAID
 Cardiovascular side effect :Except for aspirin
 Sodium and fluid retention
 Inhibition of cox2 increase risk of myocardial infarction ,stress
and thermboembolism
 Cox2 activity on endothelium serve as main source of
prostacyclin production which inhibit vessel constriction and
platelet aggregation

21. NSAID
 increased blood pressure
 All NSAIDS can increase blood pressure whether or not you already
have high blood pressure .
 NSAIDs may also reduce the effect of some blood pressure
medications.
 On average, NSAIDs can increase blood pressure by 5 millimeters of
mercury

22. NSAID
 Hepatotoxicity
 Clearance of NSAID is predominantly by hepatic metabolism
 Elevation of liver enzymes
 Diclofenac cause transminitis more common than other NSAID
 Severe hepatitis reported with indomethcin

23. NSAID
 Allergic reactions
Allergic reactions to NSAIDs are rare
 Bruising or bleeding
NSAIDs can reduce your blood’s ability to clot. This may cause
you to bruise more easily. Small cuts may take longer to stop
bleeding.
The effect can be serious if you also take warfarin (Coumadin).

24. NSAID
 The cox2 enzyme play several role in female reproductive cycle
 As cox2 mediated prostaglandin are involoved in follicle rupture
 Cox2 important in implantation of embryo in the uterus
 Prostaglandin have role in uterine contraction during labour

25. NSAID
 NSAID and pregnancy:
 NSAID in first and second trimester is relatively safe
(categeroy B)
 Use of NSAID after 32 weeks of gestation should be avoided as
prostaglandin are necessary in late pregnancy to maintain
patent ductus arteriosus ,for fetal kidney devlopment and for
labour progression

26. NSAID
 Hyper sensitivty reaction:
 Asthma, nasal polyp, aspirin sensitivty ( samter triad)
 Sensetivity not allergy because it is not immunoglobulin E mediated
 Caused by cyclooxygenase inhibition result in decrease prostaglandin
production E2 an important bronchodilator
 5 fold increase bronchial expresion of leukotriene c4 when aspirin or
other NSAID block cyclooxgynease the archodonic acid are diverted
down the leukotrien pathway result in excessive production of
leukotrienes C,D and E

27. NSAID
 Possible effects on bone and soft tissue healing​:
O It has been hypothesized that NSAIDs may delay healing from bone
and soft-tissue injuries by inhibiting inflammation.
O On the other hand, it has also been hypothesized that NSAIDs might
speed recovery from soft tissue injuries by preventing inflammatory
processes from damaging adjacent, non-injured muscles.
O There is moderate evidence that they delay bone healing.Their overall
effect on soft-tissue healing is unclear

28. NSAID
 Aspirin cause
 injury of superficial mucosa (no perforation)
 Anti platelet
 if given with other NSAID can cause perforation
Aspirin taken 8 hours after NSAID
NSAID taken 2 hours after aspirin
Aspirin at low dose increase uric acid
High dose aspirin decrease uric acid