NON-STEROIDAL

ANTI-INFLAMMATORY DRUGS
)NSAIDs(
Definition
Drugs that inhibit inflammation by preventing
the synthesis of prostanoids.
Mechanism of Action
Inhibit prostanoids synthesis by inhibiting
cyclo-oxygenase )COX-1 and COX-2( enzymes.

Aspirin inhibits the enzyme irreversibly

(acetylation of serine residue)
 Additional mechanism of Action of
Aspirin

 Induction of the generation of anti-

inflammatory lipoxins (aspirin-triggered
lipoxins or ATLs)
 PHARMACOLOGICAL ACTIONS
OF NSAIDs

 Analgesic
 Anti-inflammatory

 Antipyretic
 Anti-platelet )aspirin(
 CLASSIFICATION OF NSAIDs
Non-selective )COX-1/COX-2( inhibitors

Group Examples

Salicylates  Aspirin
 Paracetamol
Aniline derivatives
(acetaminophen)
Indol derivatives  Indomethacin

Propionic acids  Ibuprofen

Oxicams  Piroxicam
CLASSIFICATION OF NSAIDs )cont’d(

Selective COX-2 inhibitors

Group Examples

Pyrazole derivatives Celecoxib

Furanone derivative Rofecoxib
 CLINICAL USES OF NSAIDs

Aspirin/salicylates - thromboembolism
- stroke
- myocardia infaction
- fever and pain

Paracetamol - fever and pain

)no effect on inflammation(
 CLINICAL USES OF NSAIDs )cont’d(

Indomethacin - rheumatoid arithritis

- gout
- malignancy-associated
fever

Others:
)ibuprofen, - as alternatives
naproxen,
piroxicam,
mefenamic acid(
 ADVERSE EFFECTS OF NSAIDs
GIT
Gastric erosion, ulceration and bleeding
Skin
Skin reactions )rashes, urticaria or
photosensitivity(
Renal
Acute renal failure: (patients with high vasoconstrictor
catecholamine and angiotensin II
(e.g., liver cirrhosis, congestive heart failure, etc).
Aspirin-specific adverse effects

 Salicylism )dizziness, deafness and tinnitus(

 Asthma in aspirin-sensitive asthmatics
 Reye’s syndrome )hepatic encephalitis(
 Bleeding disorders )esp. with warfarin(
 Respiratory and metabolic acidosis )poisoning(
 GOUT

Definition

A metabolic disease of purine overproduction

leading to deposition of urate crystals in joints
which in turn evokes acute inflammatory joint
pain.
 Drug treatment
a. Inhibition of uric acid synthesis – allopurinol
)drug of choice(

b. Enhancement of uric acid excretion –

probenecid and sulphinpyrazone )uricosuric
agents(
c. Inhibition of leukocyte accumulation in the
joint – colchicine
d. General inhibition of inflammation and pain –
NSAIDs )except aspirin(
 MECHANISM OF ANTI-GOUT ACTION OF
O
ALLOPURINOL O Hypoxanthine
Allopurinol N
HN HN1 6 5 7
N 2 8
3 4 9
N N N
N H
H
Xanthine oxidase Xanthine oxidase O
Xanthine
N
O HN

HN
N N
N O H H
N N Xanthine oxidase
O H H
O
H
Alloxanthine N
HN
Uric acid O
N N
O H H
 LEARNING OBJECTIVES

Describe the mechanism of action of NSAID .1

Contrast the actions of aspirin with other NSAIDs .2

Understand the adverse effects of NSAIDs and the role .3

of COX inhibition

.List aspirin-specific adverse effects .4

.(Describe the clinical uses of NSAID (with drugs if choice .5

.Describe the mechanisms by which anti-gout drugs act .6