Non-steroidal anti-inflammatory drugs

Drug names

Non selective COX inhibitors (DIAMOND)

Diclofenac sodium, ibuprofen, indomethacin, aspirin, mefanamic acid, naproxen

Selective COX2 inhibitors

1st gen : celecoxib

2nd gen : parecoxib

Mechanism of action

NSAIDs inhibit prostaglandin synthesis by inhibiting cyclooxygenase enzyme.

Cox1 is non inducible and present mainly in platelet, stomach and kidney. It is responsible for
synthesis of prostaglandins involved in GI cytoprotection, platelet aggregation, renal blood flow
maintenance and renal electrolyte homeostasis.

Cox2 is induced by cytokines and are involved in pain, fever and inflammation. Cox2 also
generates prostacyclin and inhibition of Cox2 leads to thrombosis.

Pharmacological Actions of NSAIDs

1. Analgesia - relieve pain of mild to moderate intensity from somatic origin

2. Anti-inflammatory action - by inhibiting PGE2, I2 and F2alpha synthesis
3. Antipyretic action - lowers the elevated temperature rapidly and effectively
4. Antiplatelet effect - irreversible acetylation of platelet COX, inhibit platelet aggregation
and adhesion due to reduced production of thromboxane A2 >> prevent thrombosis and
prolong bleeding time
5. Gl irritation - due to back diffusion of acid causes injury to mucosa and submucosal
capillaries resulting in necrosis bleeding, inhibition of protective prostaglandin synthesis
(PGE2 & PG12) causes increased acid secretion and decreased mucous production
6. Effect on renal hemodynamics - salt and water retention and oedema due to inhibition of
renal vasodilator PG E2 and PG I2 synthesis
 7. Effect of uric acid excretion (in Aspirin) - decrease urate excretion and increase plasma
urate concentration
8. Closure of ductus arteriosus in fetus (indomethacin)
9. Effects on CNS - stimulation of CNS followed by depression: confusion,
dizziness, tinnitus, convulsion and coma, stimulate respiration with
therapeutic dose produces hyperventilation
10. Local effect: (only in salicylates) irritating to skin & mucosa and destroy epithelial cells
(keratolytic action)

Therapeutic Uses of NSAlDs

A. Systemic administration:
1. non-specific relief of certain types of pain
e.g., headache, arthralgia, myalgia, toothache and dysmenorrhea and to reduce fever

2. to reduce inflammation e.g., acute rheumatic fever, rheumatoid arthritis

3. prophylaxis of thrombo-embolic diseases e.g., coronary heart disease, deep vein thrombosis

(Aspirin low dose)

4. for the closure of patent ductus arteriosus (indomethacin is more useful)

B. Local application
1. Muscle and joint pain (topically)
2. Warts, fungal infection (salicylic acid)
3. Ulcerative colitis (orally)

Side effects of NSAIDs

1. commonest side effect, nausea and vomiting (due to stimulation CTZ & gastric irritation), heart
burn, epigastric distress, abdominal pain, erosive gastritis, exacerbation of PU, gastrointestinal
hemorrhage, perforation
2. salt and water retention and oedema, decrease effectiveness of anti-hypertensive/ diuretics,
hyperkalemia, analgesic nephropathy
 renal papillary necrosis and acute renal failure in long-termed use
3. Platelets: increased bleeding tendency in blood disorders, increased risk of hemorrhage

4. CVS: premature closure of ductus arteriosus in fetus hypertension, hypertension and MI

5. Hypersensitivity reactions or allergic reactions: rhinitis, angioneurotic oedema, asthma, urticaria,

flushing, hypotension, shock
6. CNS: Headache, vertigo, dizziness, confusion, depression, lowering seizure threshold. Aspirin high
dose produces toxic effect on CNS > stimulation followed by depression. Confusion, tinnitus,
hearing difficulty, delirium, psychosis, stupor and coma
7. Salicylate intoxication: most often occurs in children and sometimes is fatal (called salicylism).
includes headache, dizziness, tinnitus, difficulty hearing, dimness of vision, mental confusion,
nausea, vomiting, and occasionally diarrhea.

8. Reye's syndrome: caused by aspirin and other salicylates; characterized by hepatic

encephalopathy, acute febrile illness in children treated with salicylates
9. Thrombosis: selective COX-2 inhibitors
Diclofenac side effects >> same as NSAIDs