NSAIDS

NSAIDS

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs / NAIDs / NSAIAs / NSAIMs), are drugs with analgesic and antipyretic (fever-reducing) effects and which have, in higher doses, anti-inflammatory effects.

The term "Non-Steroidal" is used to distinguish these drugs from steroids, which - among a broad range of other effects - have a similar eicosanoid-depressing, anti-inflammatory action.

As analgesics, NSAIDs are unusual in that they are non-narcotic.

The most prominent members of this group of drugs are:

§  Aspirin

§  Ibuprofen

§  Naproxen

MECHANISM OF ACTION

Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes.

COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2).

Prostaglandins act (among other things) as messenger molecules in the process of inflammation.

This mechanism of action was elucidated by John Vane (1927–2004), who later received a Nobel Prize for his work. Many aspects of the mechanism of action of NSAIDs remain unexplained, for this reason further COX pathways were hypothesized.

NSAIDS have antipyretic activity and can be used to treat fever.

Fever is caused by elevated levels of prostaglandin E2, which alters the firing rate of neurons within the hypothalamus that control thermoregulation.

Antipyretics work by inhibiting the enzyme COX, which causes the general inhibition of prostanoid biosynthesis (PGE2) within the hypothalamus. PGE2 signals to the hypothalamus to increase the body's thermal set point.

Note: Ibuprofen has been shown to be more effective as an antipyretic than acetaminophen.

CLASSIFICATION

NSAIDs can be broadly classified based on their chemical structure.

PROPIONIC ACID DERIVATIVES

§  Ibuprofen

§  Naproxen

§  Fenoprofen

§  Ketoprofen

§  Flurbiprofen

§  Oxaprozin

ACETIC ACID DERIVATIVES

§  Indomethacin

§  Sulindac

§  Etodolac

§  Ketorolac

§  Diclofenac

§  Nabumetone

ENOLIC ACID (OXICAM) DERIVATIVES

§  Piroxicam

§  Meloxicam

§  Tenoxicam

§  Droxicam

§  Lornoxicam

§  Isoxicam

FENAMIC ACID DERIVATIVES

§  Mefenamic acid

§  Meclofenamic acid

§  Flufenamic acid

§  Tolfenamic acid

SELECTIVE COX-2 INHIBITORS (COXIBS)

§  Celecoxib (FDA alert)

§  Rofecoxib (withdrawn from market)

§  Valdecoxib (withdrawn from market)

§  Parecoxib FDA withdrawn

§  Lumiracoxib TGA cancelled registration

§  Etoricoxib FDA withdrawn

§  Firocoxib used in dogs and horses

USES

NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present.

Research continues into their potential for prevention of colorectal cancer, and treatment of other conditions, such as cancer and cardiovascular disease.

INDICATIONS

1)     Rheumatoid arthritis

2)     Osteoarthritis

3)     Inflammatory arthropathies (spondylitis, psoriatic arthritis)

4)     Acute gout

5)     Dysmenorrhoea (menstrual pain)

6)     Metastatic bone pain

7)     Headache and migraine

8)     Postoperative pain

9)     Mild-to-moderate pain due to inflammation and tissue injury

10)Pyrexia (fever)

11)Ileus

12)Renal colic