Non-steroidal anti-

inflammatory drugs

Stephanie Monks
NSAIDs
 Effects of NSAIDs
 Analgesic
 Antipyretic
 Anti-inflammatory

 Inhibit cyclo-oxygenase (COX) enzyme

 Therefore inhibit prostaglandin synthesis
Analgesic properties
 Peripheral (and central)

 Associated with anti-inflammatory action

 Inhibit prostaglandin synthesis

 Prostaglandins don’t cause pain, but

potentiate pain caused by other inflammatory
mediators (bradykinin)
Anti-inflammatory properties
 Prostaglandins produce vasodilatation and
increase vascular permeability

 NSAIDs therefore decrease inflammation

Antipyretic properties
 Fever caused by endogenous pyrogen (IL-1).
Released from leucocytes
Mechanism of action
 COX – enzyme that catalyses arachidonic
acid to prostaglandins and leukotrienes

 Arachidonic acid is released from membrane

phospholipids as a response to inflammatory
stimuli.

 Prostaglandins establish the inflammatory

response.
Mechanism II
Inflammatory stimuli (e.g. disease, trauma) causes membrane
phospholipids to release:
Arachidonic acid
NSAIDs

COX

Leukotrienes & Prostaglandins

Create inflammatory
response
Uses
 Mild to moderate pain
 Musculoskeletal pain and inflammation - RA,
OA, acute gout, Ankylosing spondylitis
 Dental and orofacial pain
 Dysmenorrhoea
 Fever
 Post-op anaesthesia
Examples
 Ibuprofen/Brufen (migraine,fever)

 Naproxen

 Diclofenac/Voltarol

 Indometacin (closure of ductus arteriosus)

 Mefenamic acid (menorrhagia/dysmenorrhoea)

Side-effects
 Inhibition of prostaglandin synthesis

 Other functions of prostaglandins

 protect the stomach lining
 promote clotting of the blood
 regulate salt and fluid balance
 maintain blood flow to the kidneys when
kidney function is reduced
Gastric Side-effects
 Causes damage to gastric mucosa
 Dyspepsia
 Nausea
 Gastritis

 More serious cases

 GI bleed
 Perforation
Contraindications
 Previous allergy to aspirin/NSAID

 Renal, cardiac, hepatic impairment (use of

NSAIDs may decrease renal function)

 Previous/active gastric ulceration

COX-1/COX-2
 Isoenzymes
 In tissue found as COX-1
 At sites of inflammation, cytokines stimulate
formation of COX-2

 Inhibition of COX-2  Anti-inflammatory

 Inhibition of COX-1  GI toxicity
Selective COX-2 Inhibitors
 Examples (BNF 50)
 Celecoxib (Celebrex) - Manufacturer advises avoid—no
information available
 Etodolac (Lodine) - Manufacturer advises avoid
 Meloxicam (Mobic) - No information available—manufacturer
advises avoid
 Rofecoxib (Vioxx) – withdrawn
 Valdecoxib (Bextra) - suspended
Risks of selective NSAIDs
 Increased risk of thrombotic adverse
cardiovascular reactions such as heart attack
or stroke

 Vioxx withdrawn Sept 2004

 Increased risk of MI (trial in colon cancer)
 Bextra suspended April 2005
 CV risks plus serious skin reactions
Aspirin
 Acetylsalicylic acid
 Longest-standing NSAID
 Absorbed mainly in stomach
 Hydrolysed by esterases in blood and tissues
to salicylate and acetic acid

 Adverse effects – N+V, epigastric pain,

tinnitus