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Additional mechanism of Action ofAdditional mechanism of Action of

AspirinAspirin

Induction of the generation of antiInduction of the generation of anti--

inflammatory lipoxins (aspirininflammatory lipoxins (aspirin--triggeredtriggeredlipoxins or ATLs)lipoxins or ATLs)

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Analgesic

PHARMACOLOGICAL ACTIONSPHARMACOLOGICAL ACTIONS

OF NSAIDsOF NSAIDs

Anti-inflammatory

Antipyretic

Anti-platelet (aspirin)

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CLASSIFICATION OF NSAIDsCLASSIFICATION OF NSAIDs

Non-selective (COX-1/COX-2) inhibitors

Group Examples

Salicylates Aspirin

Aniline derivatives Paracetamol

(acetaminophen)

Indol derivatives Indomethacin

Propionic acids Ibuprofen

Oxicams Piroxicam

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CLASSIFICATION OF NSAIDs (contd)CLASSIFICATION OF NSAIDs (contd)

Selective COX-2 inhibitors

Group Examples

Pyrazole derivatives

Furanone derivative Rofecoxib

Celecoxib

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CLINICAL USES OF NSAIDsCLINICAL USES OF NSAIDs

Aspirin/salicylates - thromboembolism

- stroke

- myocardia infaction- fever and pain

Paracetamol - fever and pain(no effect on inflammation)

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CLINICAL USES OF NSAIDs (contCLINICAL USES OF NSAIDs (contd)d)

Indomethacin - rheumatoid arithritis

- gout

- malignancy-associated

fever

Others:

(ibuprofen, - as alternativesnaproxen,

piroxicam,

mefenamic acid)

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ADVERSE EFFECTS OF NSAIDsADVERSE EFFECTS OF NSAIDs

Gastric erosion, ulceration and bleedingGIT

Skin reactions (rashes, urticaria or

photosensitivity)

Skin

Acute renal failure: (patients with high vasoconstrictorcatecholamine and angiotensin II

(e.g., liver cirrhosis, congestive heart failure, etc).

Renal

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Salicylism (dizziness, deafness and tinnitus)

Asthma in aspirin-sensitive asthmatics

Reyes syndrome (hepatic encephalitis)

Bleeding disorders (esp. with warfarin)

Respiratory and metabolic acidosis (poisoning)

Aspirin-specific adverse effects

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GOUTGOUT

A metabolic disease of purine overproductionleading to deposition of urate crystals in joints

which in turn evokes acute inflammatory joint

pain.

Definition

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a. Inhibition of uric acid synthesis

allopurinol(drug of choice)

b. Enhancement of uric acid excretion

probenecid and sulphinpyrazone (uricosuric

agents)

Drug treatment

c. Inhibition of leukocyte accumulation in the

joint colchicine

d. General inhibition of inflammation and pain

NSAIDs (except aspirin)

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MECHANISM OF ANTIMECHANISM OF ANTI--GOUT ACTION OFGOUT ACTION OF

ALLOPURINOLALLOPURINOL

HN

N NH

N

HN

NH

N

O NH

HN

NHO NH

HN

O

HN

NHO

NH

N

HN

NH

N

N

Xanthine oxidase

Xanthine oxidase

Xanthine oxidase

Allopurinol

Alloxanthine

Xanthine

HypoxanthineOO

O

O

O

Uric acid

61

23 4

5 7

98

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LEARNING OBJECTIVES

1. Describe the mechanism of action of NSAID

2. Contrast the actions of aspirin with other NSAIDs

3. Understand the adverse effects of NSAIDs and the role

of COX inhibition

4. List aspirin-specific adverse effects.

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

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