Unit 5.
3 Non Steroidal Anti Inflammatory Agents
[NSAIDS]
CHEMICAL CLASSIFICATION OF NSAIDS
Chemical class Drugs
Salicylic acid derivatives Sodium salicylate,
Aspirin
Anthranilic acid derivative Mefenamic acid,
Meclofenamate
Indole & Indene acetic acid derivative Indomethacin,
Sulindac [prodrug]
Heteroaryl acetic acid or Tolmetin,
Arylpropionic acid derivative Diclofenac,
Ketorolac [pyrrolo-pyrrole nucleus]
Ibuprofen,
Naproxen
Pyrrole acetic acid derivative Zomepriac,
Para amino phenol derivative Phenacetin [Prodrug ]
Acetaminophen
Pyrazole derivative Antipyrine
Oxicams or Enolic acid derivative Piroxicam
Phenylbutazone [pyrrazolidinedione nucleus]
[1] Salicylic acid derivatives/ salicylates:
Sodium salicylate,
Aspirin
Therapeutic Uses:
Antipyretic, analgesic, and anti-inflammatory agents.
Because salicylates promote the excretion of uric acid, they are useful in the treatment
of gouty arthritis.
Salicylates inhibit platelet aggregation, which can contribute to heart attacks and
stroke. Aspirin appears to inhibit prostaglandin COX in platelet membranes, thus
blocking formation of the potent platelet-aggregating factor TXA.
[2] Anthranilic acid derivative
Mefenamic acid
Meclofenamate
Anthranilic acid
Therapeutic Uses:
Mefenamic acid is the only fenamic acid derivative that produces analgesia centrally
and peripherally. Mefenamic acid is indicated for the short-term relief of moderate
pain and for primary dysmenorrhea
Meclofenamate sodium is indicated for the relief of mild to moderate pain, the acute
and chronic treatment of rheumatoid arthritis and osteoarthritis, the treatment of
primary dysmenorrhea, and the treatment of idiopathic, heavy menstrual blood loss.
[3] Indole & Indene acetic acid derivative
Indole nucleus
Indene nucleus
Indomethacin
Sulindac [Prodrug]
More potent
Therapeutic Uses:
Indomethacin is used for short-term treatment of acute gouty arthritis, acute pain of ankylosing spondylitis,
and osteoarthritis. Because of its ability to suppress uterine activity by inhibiting prostaglandin biosynthesis,
indomethacin also has an unlabeled use to prevent premature labor.
Sulindac is a prodrug and is converted to a metabolite that appears to inhibit the COX system. Sulindac is
indicated for long-term use in the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis,
and acute gouty arthritis.
Indomethacin: SULINDAC:
[1] The 5- position of the indole ring is most flexible [1] Bioactivation of sulindac to active form
with regard to the nature of substituents that
enhance activity.
[2] Substituents such as methoxy, fluoro,
dimethylamino, methyl, allyloxy, and acetyl are more
active than the unsubstituted indole ring.
[3]The presence of an indole ring nitrogen is not
essential for activity, because the corresponding 1-
benzylidenylindene analogs (e.g., sulindac) are Active form of sulindac
active.
[2] The isosteric replacement of the indole ring with the indene
ring system resulted in a derivative with therapeutically useful
antiinflammatory activity and fewer CNS and GI side effects.
[3] Z-isomer is a much more potent anti-inflammatory agent than
the corresponding E-isomer
[4] Heteroaryl acetic acid or Arylpropionic acid derivative
Drug Structure Uses
Tolmetin Tolmetin sodium is indicated for the treatment of rheumatoid
arthritis, juvenile [a form of joint disease in children]
rheumatoid arthritis, and osteoarthritis
Diclofenac Diclofenac sodium is indicated for the treatment of rheumatoid
arthritis, osteoarthritis, and ankylosing spondylitis
Ibuprofen Ibuprofen is indicated for the relief of the signs and symptoms
of rheumatoid arthritis and osteoarthritis, the relief of mild to
moderate pain, the reduction of fever, and the treatment of
dysmenorrhea.
Ketorolac Ketorolac is used as a peripheral analgesic for short term use
[pyrrolo-pyrrole nucleus] and for the relief of ocular itching caused by seasonal allergic
conjunctivitis, used for its antiinflammatory and antipyretic
activity.
Naproxen Naproxen is used to relieve pain, tenderness, swelling, and
stiffness caused by osteoarthritis (arthritis caused by a
breakdown of the lining of the joints), rheumatoid arthritis
(arthritis caused by swelling of the lining of the joints)
[5] Pyrrole acetic acid derivative
Zomepirac, introduced in 1980 as an analgesic, was withdrawn in 1983 because of
severe anaphylactoid reactions, particularly in patients sensitive to aspirin
[6] Para amino phenol derivative
Phenacetin [Prodrug ]
Acetaminophen
Acetaminophen:
Acetaminophen is indicated for use as an antipyretic/analgesic, particularly in individuals
displaying an allergy or sensitivity to aspirin. It does not possess anti-inflammatory activity,
but it will produce analgesia in a wide variety of arthritic and musculoskeletal disorders.
Phenacetin is metabolized to acetaminophen. Both phenacetin and acetaminophen
undergo hydrolysis to yield aniline derivatives that produce metabolite hydroxylamine
derivatives responsible for methemoglobinemia and hemolytic anemia [ resulted in their
removal from the US market].
The N-hydroxyamide is then converted to a reactive toxic metabolite, an acetimidoquinone
—N-acetyl-p-benzoquinoneimine responsible for hepatic and renal necrosis
Metabolism of phenacetin & Acetaminophen
Phenacetin [Prodrug]
O-demethylation
Bioactivation of Phenacetin
[7] Pyrazole derivative : Antipyrine
An analgesic and antipyretic that has been given by mouth and as
ear drops. Antipyrine is often used in testing the effects of other
drugs or diseases on drug-metabolizing enzymes in the liver.
[8] Oxicams or Enolic acid derivative :
Piroxicam
Phenylbutazone [pyrrazolidinedione nucleus]
Piroxicam
Therapeutic uses:
Piroxicam and phenylbutazone is indicated for long-term use in rheumatoid arthritis and
osteoarthritis.
Metabolism of
Tolmetin
