Nonsteroidal anti-inflammatory drugs

What are nonsteroidal anti-inflammatory drugs (NSAIDs)?

Nonsteroidal anti-inflammatory agents (usually abbreviated to NSAIDs) are a group of medicines that relieve pain and fever and reduce inflammation.

There are nearly two dozen different NSAIDs available, but they all work in the same way, and that is by blocking a specific group of enzymes called cyclo-oxygenase enzymes, often abbreviated to COX enzymes. These enzymes are responsible for the production of prostaglandins. Prostaglandins are a group of compounds with hormone-like effects that control many different processes such as inflammation, blood flow, and the formation of blood clots.

What are nonsteroidal anti-inflammatory agents used for?

NSAIDs are used to treat mild-to-moderate pain that arises from a wide range of conditions such as headaches, menstruation, migraines, osteoarthritis or rheumatoid arthritis, sprains and strains, and toothache.

Aspirin is a NSAID that is used in small doses to lower the risks of having a heart attack or a stroke caused by a blood clot. It may also be given as a single dose at the time of a heart attack to improve outcomes. This is because it irreversibly inhibits the COX-1 enzyme.

What are the differences between nonsteroidal anti-inflammatory agents?

NSAIDs may be grouped according to their preference for COX-1 and COX-2 enzymes. Those that favor COX-1 are more likely to cause gastrointestinal side effects. Those that favor COX-2 have a higher risk of cardiovascular effects but less gastrointestinal effects. Higher dosages of NSAIDs tend to result in more COX-2 enzyme inhibition (and more cardiovascular side effects), even in those NSAIDs traditionally seen as low risk (such as ibuprofen). NSAIDs with higher activity against COX-2 enzymes should be used with caution in people with cardiovascular disease or at increased risk of cardiovascular disease.

Both types of COX enzymes produce prostaglandins; however, the main function of COX-1 enzymes is to produce baseline levels of prostaglandins that activate platelets and protect the lining of the gastrointestinal tract, whereas COX-2 enzymes are responsible for releasing prostaglandins after infection or injury.

Most NSAIDs inhibit both enzymes to a certain extent.

List of Common NSAIDs

Generic name	Brand names
More COX-1 selective*
flurbiprofen	Ansaid
ketorolac	Only generic
ketoprofen	Oruvail
tolmetin	Generic
aspirin	Ecotrin, Miniprin, and generic
Relatively nonselective
ibuprofen	Advil, Motrin, Genpril
naproxen	Aleve, Flanax Pain Reliever, Naprosyn
Less than 50-fold COX-2 selective*
indomethacin	Indocin, Tivorbex
sulindac	Clinoril
piroxicam	Feldene
mefenamic acid	Ponstel
meloxicam	Mobic
diclofenac	Cataflam, Voltaren, Zipsor, Zorvolex
celecoxib	Celebrex
etodolac	Generic
More than 50-fold COX-2 selective
etoricoxib	Not approved in the U.S.
lumiracoxib	Not approved in the U.S.
rofecoxib	Withdrawn because of safety concerns

*Ranked in order from the least COX-2 activity to the highest within that group.

Note that selectivity rankings vary depending on resources used. This table is based on a best effort accumulation of data.

Are nonsteroidal anti-inflammatory agents safe?

NSAIDs are one of the most widely prescribed group of medicines; however, they are associated with some serious side effects.

NSAIDs can increase your risk of a fatal heart attack or stroke. The risk increases the higher the dosage and the longer the length of time you remain on an NSAID for. People with pre-existing heart disease are more at risk and certain NSAIDs, such as diclofenac and celecoxib, have been linked to more heart-related side effects than others. NSAIDs should never be used just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Gastrointestinal (GI) side effects are also common, and usually related to dosage and duration of treatment although some NSAIDs, such as ketorolac, aspirin and indomethacin, are associated with a higher risk. Elderly people or those taking other medicines that irritate the stomach are more likely to experience life-threatening GI side effects, such as stomach or intestinal bleeding.

Most NSAIDs are not suitable for children or adolescents under the age of 18 years. Ibuprofen is the only NSAID approved for children aged three months and older. Aspirin can increase the risk of Reye's syndrome if given to children with a viral illness. Never give aspirin to children except on a doctors advice.

Most NSAIDs should not be taken during the last three months of pregnancy or while breastfeeding except on a doctor’s advice.

What are the side effects of nonsteroidal anti-inflammatory agents?

NSAIDs can potentially cause a range of side effects, especially when used at higher than recommended dosages for long periods of time.

Gastrointestinal side effects that may occur include bloating, diarrhea, constipation, irritation of the lining of the stomach, nausea or vomiting.

NSAIDs may also affect kidney function and reduce how quickly blood flows through the kidneys. They may cause retention of sodium and water which can lead to edema and high potassium levels. Occasionally, they may cause more serious damage to the kidneys.

Some NSAIDs, particularly diclofenac and those that are selective for COX-2 enzymes, have a high risk of cardiovascular thrombotic events such as a heart attack or stroke. Other heart-related side effects such as high blood pressure, congestive heart failure, and palpitations have also been reported.

In addition, some people taking NSAIDs have experienced asthma attacks, bleeding, fatigue, headache, insomnia, low neutrophil levels, urticaria (hives), vertigo and seizures. Reye’s syndrome, a life-threatening condition that causes swelling in the liver and brain and is mostly associated with aspirin use in young children has also been reported.

 

 

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