I pulled this off a web page for arthritis. We are seeing a lot of blood
coagulation disorders with people on long term NSAID use. I'm gonna
look into it more.
The other 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 things to know 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 anti-diabetic 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: Ansaid, Arthrotec, Aspirin,
Cataflam, Clinoril, Daypro, Dolobid, Feldene, Ibuprofen, Indocin,
Ketoprofen, Lodine, Meclomen, Mobic, Nalfon, Naproxen, Ponstel,
Relafen, Tolectin, and Voltaren
Ok, not researching but thinking...
What is this saying? - 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.
Is this saying we need to regulate prostglandins better?
Antipyretic and anti-inflammatory effects of NSAIDs can mask the signs and symptoms of infection. HOW?
Long-term use of NSAIDs may have a damaging effect on chondrocyte (cartilage) function. IN WHAT WAY?
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. I had low albumin when diagnosed. I've since read that most AI people are low albumin. What does this mean to us?
Pip - typing out loud
Pip, this is just my small observation but NSAIDS seem to be the fix all, cureI know there is a book out there that says NSAID's are why we get AI diseases. Sherry Rogers? Anybody know?
Pip
I feel like it's one of those damned if we do, damned if we don't situations. I take fish oil, and it helps, but I wouldn't be able to function at all if I didn't take a NSAID. I don't want to take narcotics, so Voltaren is all I have.
I try to make sure I don't take it on an empty stomach, and I don't drink alcohol more than a few times a year. It's a risk, I know, but what other choice do I have?
My father and paternal grandmother did not take NSAIDs before getting RA, other than the occasional aspirin.NSAIDs do reduce the effects of inflammation; they can make you feel better, but do not stop the damage to the joints. An arthritis book I'm reading says that many people with RA need to take NSAIDs and it recommends that anyone on NSAIDs protect themselves from GI problems by taking medications that will reduce the risk of ulcers and GI bleeds. It also says traditional NSAIDS affect platelets and the Cox 2 selective- NSAIDs give the least amount of GI risk, but they have been linked to cardio problems and strokes. All NSAIDS( traditional and Cox 2) can on rare occaisions affect the liver and kidney. Even rarer side effects of both classes of NSAIDs are major reductions in the body's ability to make red or white blood cells.
I do think that after the problems with the Cox 2's many drs are more careful about scripting NSAIDs. My GP recently updated my med file and when he noted all the meds I'm taking said that the list scares the hell out of him. Well, I wouldn't be taking them if I didn't have too!
After being dx with Polycystic ovanian syndrome at twenty...I was given massive amounts of NSAIDs to combat the pain of that. WEll, it took about ten years or so, but my body developed a massive allergy to all classes of NSAIDs, so they are completely out in my pain control regiment. During the day...I usually take nothing, but I do have to sleep...I guess...occasionally!