EDU: NSAIDS

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The Facts Of NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)

Article by Carol & Eustice,

More information found at

http://arthritis.about.com/cs/nsaids/a/factsofnsaids.htm

NSAIDs Are Among The Most Commonly Prescribed Arthritis Drugs

NSAIDs combat arthritis by interfering with the inflammatory process.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a large group of drugs

commonly used to treat arthritis because of their:

* analgesic (pain-killing) properties

* anti-inflammatory properties

* antipyretic (fever-reducing) properties

NSAIDs commonly used for arthritis include:

# Ansaid (generic name flurbiprofen)

# Arthrotec (generic name diclofenac with misoprostol)

# Aspirin (acetylated / non-acetlyted salicylates)

# Cataflam (generic name diclofenac potassium)

# Celebrex (generic name celecoxib)

# Clinoril (generic name sulindac)

# Daypro (generic name oxaprozin)

# Dolobid (generic name diflunisal)

# Feldene (generic name piroxicam)

# Ibuprofen (brand names include Motrin, Advil, Mediprin, Nuprin, Motrin IB)

# Indocin (generic name indomethacin)

# Ketoprofen (brands names include Orudis, Oruvail, Actron, Orudis KT)

# Lodine (generic name etodolac)

# Meclomen (generic name meclofenamate sodium)

# Mobic (generic name meloxicam)

# Nalfon (generic name fenoprofen)

# Naproxen (brand names include Naprosyn, Aleve, Naprelan, Anaprox)

# Ponstel (generic name mefanamic acid)

# Relafen (generic name nabumetone)

# Tolectin (generic name tolmetin sodium)

# Voltaren (generic name diclofenac sodium)

How NSAIDs Work

The mechanism of action of NSAIDs is the inhibition of the enzyme

cyclooxygenase, which catalyzes arachidonic acid to prostaglandins and

leukotrienes. Arachidonic acid is released from membrane phospholipids as a

response to inflammatory stimuli. Prostaglandins establish the inflammatory

response. NSAIDs interfere with prostaglandin production by inhibiting

cyclooxygenase.

This mechanism may relate to the variation in response between patients.

Scientific studies have shown a correlation between concentration of the

drug and effect, but do not explain the differences in individual patient

responses. It is thought that the pharmacokinetic (process by which a drug

is absorbed, distributed, metabolized, and eliminated) differences among the

various NSAIDs may account for the variability in response.

# Inflammation - Test Your Knowledge

The Enzyme Cyclooxygenase

Further research of the enzyme cyclooxygenase, also known as COX, has

revealed that there are two forms, known as COX-1 and COX-2. NSAIDs affect

both forms of cyclooxygenase. COX-1 is involved in maintaining healthy

tissue, while COX-2 is involved in the inflammation pathway. COX-2 selective

inhibitors became the newest subset of NSAIDs born of this research.

FDA Actions For All NSAIDs

In April 2005, The U.S. Food and Drug Administration announced actions which

will be taken regarding the marketing of NSAIDs. The actions include changes

for COX-2 inhibitors, as well as prescription and non-prescription

(over-the-counter) NSAIDs. The actions by the FDA follow scrutiny of NSAIDs

and COX-2 inhibitors provoked by the voluntary withdrawal of the COX-2

selective inhibitor Vioxx in September 2004.

# FDA Announces Changes For All NSAIDs

# Questions And Answers: FDA Regulatory Actions On COX-2 Inhibitors And

NSAIDs

Other Facts About NSAIDs

# Pain and inflammation sometimes occur in a circadian rhythm (daily

rhythmic cycle based on a 24 hour interval). Therefore NSAIDs may be more

effective at certain times.

# NSAIDs can be divided into two groups: those with plasma (blood)

half-lives less than 6 hours (i.e. aspirin, diclofenac, ibuprofen) and those

with half-lives greater than 10 hours (i.e. diflunisal, piroxicam, and

sulindac). Since it takes three to five half-lives to stabilize blood

levels, NSAIDs with longer half-lives require a loading dose to be given

(large dose given initially). The " half-life " is the time it takes a drug to

go down to half of its initial level.

# Prostaglandins, which are inhibited by NSAIDs, function in the body to

protect the stomach lining, promote clotting of the blood, regulate salt and

fluid balance, and maintain blood flow to the kidneys when kidney function

is reduced. By decreasing prostaglandins, NSAIDs can cause stomach

irritation, bleeding, fluid retention, and decreased kidney function.

# Synovial fluid (joint fluid) concentrations are 60% of plasma

concentrations regardless of type of NSAID or its half-life. Synovial fluid

is mostly the site of action of NSAIDs.

# NSAIDs are 95% albumin (protein) bound. The unbound fraction of the NSAID

is increased in patients with low albumin concentrations such as in active

rheumatoid arthritis and the elderly.

More Facts About NSAIDs

# Since NSAIDs bind to plasma proteins they may be displaced by or may

displace other plasma-bound drugs such as coumadin, methotrexate, digoxin,

cyclosporine, oral antidiabetic agents, and sulfa drugs. This interaction

can enhance either therapeutic or toxic effects of either drug.

# Due to their different chemical properties some NSAIDs have substantial

biliary (bile ducts, gallbladder) excretion (i.e. indomethacin , sulindac)

and others are metabolized pre-excretion, while a few are excreted in the

urine unchanged.

# NSAID studies which have shown a variation in patient response attribute a

lower rate of adherence to one NSAID when other NSAIDs are known to be

available. The response to and preference of an NSAID may relate to more

than just symptom control.

# About 60% of patients will respond to any single NSAID.

A trial period of three weeks should be given for anti-inflammatory

effectiveness to be observed. About 10% of rheumatoid arthritis patients

will not respond to any NSAID.

# Antipyretic and anti-inflammatory effects of NSAIDs can mask the signs and

symptoms of infection.

# Adverse effects of NSAIDs which can occur at any time include renal

(kidney) failure, hepatic (liver) dysfunction, bleeding, and gastric

(stomach) ulceration.

# NSAIDs (particularly indomethacin) can interfere with the pharmacologic

control of hypertension and cardiac failure in patients who take

beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, or

diuretics.

# Long-term use of NSAIDs may have a damaging effect on chondrocyte

(cartilage) function.

Which NSAID Is Best?

It can not be predicted which NSAID will best serve a particular patient. No

single NSAID has been proven to be superior over the others for pain relief.

Once an NSAID is selected, the dosage should be increased until pain is

relieved or until the maximum tolerated dose has been reached. The duration

of analgesia does not always correspond with the plasma half-life of the

NSAID. The patient response should be a guideline for selecting the proper

dose, using the lowest dose possible to obtain pain relief. Speak with your

doctor to find out what's the best method of treatment.