The Facts Of NSAIDs

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The Facts Of NSAIDs

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

used to treat arthritis because of their analgesic (pain-killing),

anti-inflammatory, and antipyretic (fever-reducing) properties. 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.

inflammatory stimuli (disease, trauma)---->membrane phospholipids release

arachidonic acid--->cyclooxygenase catalyzes arachidonic acid to

prostaglandins and leukotrienes---->prostaglandins create an 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.

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 are 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.

---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.

---A study in the United Kingdom revealed ibuprofen as the lowest risk for

causing serious upper gastrointestinal distress. Naproxen, indomethacin, and

diclofenac were viewed as an intermediate risk. Azapropazone, and piroxicam

had the highest risk.

---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.

---Commonly used NSAIDs include: Voltaren, Dolobid, Nalfon, Ansaid, Motrin,

Indocin, Orudis, Meclomen, Naprosyn, Feldene, Clinoril, Tolectin, Daypro,

Relafen.

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.

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