(ĐTĐ) - Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, are drugs with analgesic and antipyretic (fever-reducing) effects and which have, in higher doses, anti-inflammatory effects (reducing inflammation). The term "nonsteroidal" 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.

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NSAIDs are sometimes also referred to as nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) or nonsteroidal anti-inflammatory medicines (NSAIMs). The most prominent members of this group of drugs are aspirin, ibuprofen, and naproxen partly because they are available over-the-counter in many areas.

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 (see Mechanism of action of aspirin). Many aspects of the mechanism of action of NSAIDs remain unexplained, for this reason further COX pathways were hypothesized. The COX-3 pathway was believed to fill some of this gap but recent findings make it appear unlikely that it plays any significant role in humans and alternative explanation models are proposed.

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. Ibuprofen has been shown to be more effective as an antipyretic than acetaminophen. Arachidonic acid is the precursor substrate for cyclooxygenase leading to the production of prostaglandins F,D & E.

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 (Safety alert by FDA)
• 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

Examples

NSAIDs within a group will tend to have similar characteristics and tolerability. There is little difference in clinical efficacy among the NSAIDs when used at equivalent doses. Rather, differences among compounds tend to be with regards to dosing regimens (related to the compound's elimination half-life), route of administration, and tolerability profile. Some more common examples are given below.

Sulphonanilides

• Nimesulide (systemic preparations are banned by several countries for the potential risk of hepatotoxicity)

Others

• Licofelone

Licofelone acts by inhibiting LOX (lipooxygenase) & COX and hence known as 5-LOX/COX inhibitor.

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.

NSAIDs are generally indicated for the symptomatic relief of the following conditions:

Rheumatoid arthritis

• Osteoarthritis
• Inflammatory arthropathies (e.g. ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome)
• Acute gout
• Dysmenorrhoea (menstrual pain)
• Metastatic bone pain
• Headache and migraine
• Postoperative pain
• Mild-to-moderate pain due to inflammation and tissue injury
• Pyrexia (fever)
• Ileus
• Renal colic
• They are also given to neonate infants whose ductus arteriosus is not closed within 24 hours of birth

Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of platelet aggregation. This is useful in the management of arterial thrombosis and prevention of adverse cardiovascular events. Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane -A.

In 2001 NSAIDs accounted for 70,000,000 prescriptions and 30 billion over-the-counter doses sold annually in the United States.