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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.