1. Non-steroidal anti-inflammatory drugs (NSAIDs)
Dr Sasan Zaeri
(PharmD, PhD)
Department of Pharmacology

2. Inflammatory cascade Triggers
Infection
Tissue and/or
vessel damage
Inflammatory
Mediators
Acute Inflammatory Response
Note this is a common & non-specific response
- Redness
- Heat
- Swelling
- Pain

3. Drugs block production or effect of inflammatory mediators
Tissue and/or
vessel damage
Infection
Inflammatory Mediators
Vasoactive peptides:
Histamine,serotonin
The kinin system
Coagulation cascade
The complement system
Arachidonic Acid
metabolites
NSAIDs
Corticosteroids

4. Inflammatory Enzymes: PLA2 & COX
3. Zileuton
Montelukast,
zafirlukast
2.NSAIDS
1. Steroids
Phospholipase A2
Arachidonic acid (AA)
Lipoxygenase
Cyclooxygenase (COX)
Lipoxygenase products
(leukotrienes)
Prostaglandins & thromboxanes
Inflammatory effects
(inducible)
Homeostatic
Functions
(stomach mucus)
Inflammatory effects
(esp. in asthma)

6. COX-1 vs. COX-2

7. NSAIDs- MeChanism OF ACTION
Non –Selective NSAIDs inhibit both COX-1 & COX-2 reversibly
Ibuprofen, Diclofenac, Indomethacin, Naproxen, Mefenamic acid etc.
Aspirin (irreversible COX inhibitor)
Selective NSAIDs inhibit only COX-2 reversibly
Celecoxib

8. Pharmacological Actions of Non-Selective NSAIDs
Analgesic
Antipyretic (Drug that lowers the elevated body temperature to normal)
Anti-inflammatory
Anti-platelet
Exceptions: celecoxib, non-acetylated salicylates

9. THERAPEUTIC USES SHARED BY NS-NSAIDs
Fever
Analgesic
Headache
Migraine
Dental pain
Common cold

10. THERAPEUTIC USES SHARED BY NS-NSAIDs
Rheumatoid arthritis
Osteoarthritis
Myositis
or other forms of inflammatory conditions
Dysmenorrhea

11. Adverse effects shared by NS-NSAIDs
GIT upsets ( nausea, vomiting)
GIT bleeding & ulceration
Bleeding
Hypersensitivity reaction
Inhibition of uterine
contraction
Salt & water retention

13. Dose Dependent Therapeutic Effects Of Aspirin
Antithrombotic
Antipyretic,
Analgesic
Anti-inflammatory
Daily dose of aspirin (g) 1 2 3 4 5

14. Normal physiologic interaction between PGI2 and TXA2
Blood Vessel Wall
Endothelial Cell (COX-2)
Platelet (COX-1)
Arachidonic acid
PGH2
Prostacyclin (PGI2)
Arachidonic acid
PGH2
Thromboxane (TXA2)
 cAMP/vessel smooth muscle relaxes
 Ca2+  aggregation
cAMP  aggregation
 Ca2+/vessel smooth muscle constricts
Normal physiologic interaction between PGI2 and TXA2
in platelet and endothelial cell biology

15. Added Clinical uses Antiplatelet/Antithrombotic effect
Decreases platelet production of TXA2 by COX-1 irreversibly to limit platelet aggregation and vasoconstriction
Cardioprotective (reducing the risk of MI)

16. Acute rheumatic fever
Prevention of pre-eclampsia
Chronic gouty arthritis with
large doses
Chronic use of small doses , reduce the incidence of cancer colon

17. Adverse Effects Related to : (A) Therapeutic Doses Of Aspirin
Aspirin asthma
Reye's syndrome
Syndrome of hepatic injury & encephalopathy in kids treated with aspirin after a viral illness

18. Aspirin-induced
asthma

19. Adverse Effects Related to ( B) Large doses or prolonged use of aspirin
Salicylism ( ringing of ear( tinnitus) , vertigo)
Hyperthermia
GI ulcer and bleeding
Metabolic acidosis

20. ADVERSE effects Related to High doses

21. Contraindications Children with viral infections
Patients with GI ulcer or upper GI bleeding
Patients with hemophilia
Patients with Aspirin-induced asthma

22. PARACETAMOL (acetaminophen)
Commonly used as analgesic antipyretic drug

23. Clinical uses of paracetamol
Can be used safely in patients with:
Peptic or gastric ulcers
Bleeding tendency
Allergy to aspirin
Viral infections in children
Pregnancy

24. Adverse Effects Mainly on liver due to its active metabolite
( N-acetyl-p-benzoquinone)
Large doses cause liver necrosis
Treatment Of toxicity of paracetamol:
N- acetylcysteine : SH- donor to neutralize the toxic metabolite

25. Acetaminophen Toxicity
induction
alcohol

26. DICLOFENAC Clinical uses
Treatment of rheumatoid arthritis , osteoarthritis (accumulates in synovial fluid in Long-term use )
Analgesic
Antipyretic
Acute gouty arthritis
Locally to prevent post-operative ophthalmic inflammation

27. Selective COX-2 inhibitors
General advantages :
Adverse effects are slighter than other NSADs
No effect on platelet aggregation (COX-1)
Long-term studies of the incidence of clinically significant gastrointestinal ulcers and bleeding are not yet completed

29. Adverse effects Renal toxicity Cardiovascular (high risk of MI)
Rofecoxib and valdecoxib were withdrawn

30. STILL ON THE MARKET

31. GENERAL CLINICAL USES
Rheumatoid arthritis
Osteoarthritis
Acute musculoskeletal pain
Dysmenorrhea
They can also be used in patients with gastric ulcer , haemophilia for the above indications