Non-steroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a drug class FDA-approved for use as

antipyretic, anti-inflammatory, and analgesic agents. These effects make NSAIDs useful for treating
muscle pain, dysmenorrhea, arthritic conditions, pyrexia, gout, migraines, and used as opioid-sparing
agents in certain acute trauma cases.

Classifiaction-

1. Non-selective NSAIDs-
A. Salicylates- Aspirin (acetylsalicylic acid), Diflunisal (Dolobid), Salicylic acid and its salts
B. Propionic acid derivatives- Ibuprofen, Dexibuprofen, Naproxen, Fenoprofen, Ketoprofen,
Dexketoprofen, Flurbiprofen, Oxaprozin, Loxoprofen, Pelubiprofen, Zaltoprofen
C. Acetic acid derivatives- Indomethacin, Tolmetin, Sulindac, Etodolac, Ketorolac, Diclofenac,
Aceclofenac, Bromfenac and Nabumetone
D. Enolic acid (Oxicam) derivatives- Piroxicam, Meloxicam, Tenoxicam, Droxicam,
Lornoxicam, Phenylbutazone (Bute)
E. Anthranilic acid derivatives (Fenamates)- Mefenamic acid, Meclofenamic acid, Flufenamic
acid, Tolfenamic acid
2. Selective NSAIDs
A. Celecoxib (FDA alert
B. Rofecoxib (withdrawn from market)
C. Valdecoxib (withdrawn from market)
D. Parecoxib (FDA withdrawn)
E. Lumiracoxib TGA cancelled registration
F. Etoricoxib not FDA approved, licensed in the EU
G. Firocoxib used in dogs and horses
H. Sulfonanilides-Nimesulide (systemic preparations are banned due to hepatotoxicity)
I. Others- Clonixin
J. Licofelone acts by inhibiting LOX (lipooxygenase) and COX

Mode of action-
 The main mechanism of action of NSAIDs is the inhibition of the enzymes cyclooxygenase
(COX) and Lipoxygenase (LOX).
 Cyclooxygenase convert arachidonic acid into thromboxanes, prostaglandins and prostacyclins.
Lipoxygenase (LOX) is a kind of rate-limiting enzyme in the process of arachidonic acid
metabolism into leukotriene (LT) which mediates the occurrence of inflammation.
 There are two cyclooxygenase isoenzymes, COX-1 and COX-2. COX-1 gets expressed in the
body, and it plays a role in maintaining gastrointestinal mucosa lining, kidney function, and
platelet aggregation. COX-2 is expressed in the body during an inflammatory response.
Pharmcology of Non-selective NSAIDs-
Aspirin
Aspirin was first introduced by Bayer in 1899. Aspirin and the other Salicylates reduce the signs
and symptoms of inflammation and exhibit a broad range of pharmacologic activities, including
analgesic, antipyretic, and antiplatelet properties.
Intermediate doses (650 mg to 4 g/day) inhibit COX-1 and COX-2, blocking prostaglandin (PG)
production, and have analgesic and antipyretic effects. Prostaglandins are potent, irritating substances
that have been shown to cause headaches and pain. Prostaglandins increase the sensitivity of pain
receptors and substances such as histamine and bradykinin.

The inhibition of platelet aggregation by Salicylates occurs because its interference with thromboxane
A2 in platelets, caused by COX-1 inhibition. Thromboxane A2 is an important lipid responsible for
platelet aggregation, which can lead to clot formation and future risk of heart attack or stroke.
In general, acetylsalicylic acid is involved in the interference of various cancer signaling pathways,
sometimes inducing or upregulating tumor suppressor genes. On long-term use of ASA causes
prevention of several types of cancer (stomach, colorectal, pancreatic, and liver cancers).

Pharmacokinetics-
 Absorption- Absorption is generally rapid and complete by oral administration 
 Distribution- widly distributed, 50% to 90% bound to plasma protein, cross placental barrier
 Metabolism- metabolized in the liver
 Excreation- Excreted in urine through kidney
 Half-life- 3.5- 4 hours

Advese effects-