2nd Year MBBS Student at GMERS Medical College, Junagadh.

2. Non Steroidal Anti-Inflammatory Drugs
-All drugs grouped in this class have analgesic,
antipyretic and anti-inflammatory actions in different
measures.
Do not depress CNS
Do not produce physical dependence
Have no Abuse Liability
Weaker Analgesia (except- Inflammatory pain, they are more useful)

3. 1. Willow Bark – Salix Alba – Salicylic Acid was obtained
2. 1875 – Sodium Salicylate – Fever and Pain
3. 1899 – Aspirin – Acetylsalicylic Acid
4. 1899 – Phenacetin & Antipyrine
5. 1949 – Phenylbutazone (Almost comparable to corticosteroids)
6. 1963 – Indomethacin
7. Propionic acid derivative – Ibuprofen – Recognition of
COX inhibition
8. Addition of Selective COX-2 inhibitors

5. Membrane phospholipids
Arachidonic acid
Leukotrienes Prostaglandins Thromboxane Prostacyclin
Prostanoids
COX
Phospholipase
Non Steroidal Anti-Inflammatory Drugs (NSAIDs) mainly
produce their effects by inhibiting the biosynthesis of Prostanoids.

6. In 1971, Vane and co-workers made the observation that
aspirin and some NSAIDs blocked Prostaglandins generation.
This is the major mechanism of action of NSAIDs.

7. COX-1
• Physiologically expressed
• Maintains the normal
(house keeping) function.
• Expressed in ..
– Platelets
– GIT
COX-2
• Induced in pathological
states (mostly)
• Physiologically expressed in
Kidney, Brain & Foetus.
Most of the NSAIDs inhibit COX-1 and COX-2 non-selectively,
But now some selective COX-2 inhibitors have been produced.
Cyclo-oxygenase enzyme that
plays major role in synthesis
of
PROSTANOIDS.

8. Action COX-1/COX-2
Inhibitors
COX-2
Inhibitors
Analgesic + +
Antipyretic + +
Antiinflammatory + +
Antiplatelet aggregatory + -
Gastric Mucosal Damage + -
Renal salt/water retention + +
Delay/Prolongation of labour + +
Ductus Arteriosus Closure + ??
Aspirin Sensitive Asthma Precipitation + -

9. • How pain/hyperalgesia is produced???
PGs, by affecting transducing property of free nerve endings
induce hyperalgesia.
So that, stimuli that was not eliciting pain first, can elicit now.
• How analgesia is produced???
NSAIDs inhibit synthesis of PGs (also in spinal dorsal horn
neurones as well as in brain)
Also blocks pain sensitizing mechanisms by -TNFα
-Bradykinin
-Interleukins

12. • How Fever is Produced?
However, Fever can
also be produced by
NON-PG mechanisms.

13. • How antipyresis is Produced?
In Normal
Individuals,
There is no
Hypothermia.

14. • How Inflammation takes place?
Increased Capillary Permeability
Activation Of Kininogens
Infiltration of leucocytes
Vasoconstriction in Capillaries
Vasodilation in some vascular beds
Leukotrienes
PAF
Cytokines

15. Increased Capillary Permeability
Activation Of Kininogens
Infiltration of leucocytes
Vasoconstriction in Capillaries
Vasodilation in some vascular beds
Leukotrienes
PAF
Cytokines
• Majorly NSAIDs exhibit anti-inflammatory action by inhibition
of COX-2 enzyme but in initial stages of inflammation there is
also inhibition of COX-1 enzyme.
Inhibits synthesis

16. ANTI-INFLAMMATORY POTENCY α COX INHIBITORY PROPERTY
• Certain NSAIDs may act by additional mechanisms like…
1) Inhibition of chemotaxis
- by inhibiting expression of adhesion molecules on activated
endothelial cells.
- by inhibiting expression of selectins and integrins on
inflammatory cells.
2) Generation of superoxide/free radicals.
3) Growth Factors, Lymphocyte transformation factors and TNFα
may also be affected.
e.g. Nimesulide is potent Anti-inflammatory but weak COX Inhibitor. This is due to additional
actions
• Majorly…

17. PGs(PGF2α)cause dysmenorrhoea.Dysmenorrhoea
• NSAIDs lower levels of Uterine PGs and can relieve in 60-
70%.
PGs can trigger labour and also facilitate progression.Parturition
• NSAIDs have potential to retard or delay labour.
PGE2 can keep ductus arteriosus patent.
Ductus arteriosus
closure
• NSAIDs can cause closure of ductus arteriosus if it fails naturally…
• (NSAIDs in pregnancy can cause premature closure though…
• So NSAIDs prescription near term should be avoided…)

18. PGI2
Predominantly
- Inhibition of platelet aggregation
- Bleeding time is prolonged
TXA2
*Risk of Post-Partum Haemorrhage is increased in pregnancy*
*Risk of surgical bleeding and anti-coagulant associated bleeding is
increased*

19. • Gastric Mucosal Damage:-
This is due to inhibition of COX-1 mediated synthesis of
gastroprotective PGs (PGE2 & PGI2).
Gastric Pain, Mucosal Erosion & NSAIDs induced Gastric Ulcers
are common considerations.
Relative gastric damage is the parameter for choice of NSAIDs.
• Anaphylactoid Reactions:-
Can occur to sensitive persons.
e.g. Precipitation of Asthma, Angioneurotic swellings, Urticaria…
Inhibition of COX leads to consequent diversion of Arachidonic acid to
Leukotrienes which may be the reason for this, however there is no
proof.

20. • Role of Renal PGs….
Hypovolaemia
Decreased Renal Perfusion
Sodium Loss
Induces
PG
Synthesis
ADH action oppose
Vasodilatation
Chloride Reabsorption Inhibition
• Role of NSAIDs….
COX-1 dependant impairment of blood flow and GFR reduction
Inhibition of Juxtaglomerular COX-2 dependant Sodium and water reabsorption
Can cause papillary necrosis
Can cause analgesic nephropathy
• Contra-Indicated in…
CHF
Hypovolaemia
Hepatic Cirrhosis
In Patients receiving diuretics and antihypertensives,
Sodium Retention and oedema can occur; diuretic and
antihypertensive effects are blunted.