NSAIDs:
Nonsteriodal anti-inflammatory drugs (NSAIDs) is a type of medicine that reduces pain and swelling.
However,they do not prevent further joint damage. Two common NSAIDs are Aspirin and Advil. NSAIDs have analgestic and anti-inflammatory
properties. NSAIDs reduce pain when taken at low dose and relieve inflammation when taken at a higher dose. NSAIDs such as
ASA (Aspirin,Anacin etc.) and Ibuprofen (Motrin IB,Advil etc.) can be purchased without a prescription. Examples of other
NSAIDs that require a prescription include Naprosyn, Relafen, Indocid, Voltaren, Feldene and Clinoril. The various NSAIDs
and Aspirin if taken in full doses usually have the same levels of anti-inflammatory effect. However,different individuals
may experience greater relief from one medication then another. Taking more than one NSAID at a time increase the possibility
of side effects,particularily stomach problems such as ulcers and (GI) bleeding. People taking these medications should consider
a stomach protectant such as misoprostol (Cytotec).
At over-the-counter,NSAIDs are among the best antidotes for arthritis pain. At prescription doses they are effective
fighters of both pain and inflammation. But this relief may come at a cost for some patients-stomach problems. Acetominophen
is not a NSAID but is a excellent analgestic (pain relieving) taken in combination by many patients but consult your physician
as to doseage. ACR recommends it for the pain of osteoarthritis. There has been some recent research on high doseage that
is adverse.
Because ulcers are a potentially harmful side effect of NSAID use, a new option was recently brought to market. The newest
class of NSAIDs called cyclooxygenase-2 (Cox-2) inhibitors are safer to the stomach.Vioxx (Rofecoxib) and Celebrex
(Celecoxib) are two such drugs. A new Cox-2 inhibitor called Baldecoxib (Bextra) was approved in 11/01
for treating RA and OA. They are designed to not interfere with Cox-1 (stomach-lining protector).
One downside of these drugs is that research has shown that they may not provide protection against heart disease as
a traditional NSAID might,so ask the doctor about the advisability of using it,along with low-dose aspirin or other heart-protective
medication, particularily,if one have heart disease or risk factors of it. Patient prone to infections should inform
their physician.
DMARDs:
Disease modifying anti-rheumatic drugs (DMARDs) may be prescribed when inflammation continues for
more than 8 weeks or when RA strikes many parts at once. DMARDs target the cells in the immune system causing the inflammation,but
do not reverse permanent joint damage. The gold standard is metrotrexate in the U.S. Gold salts,sulfasazine,,hydroxychlorine,chloroquine
and azathlopine are also employed. A DMARD is usually prescribed in addition to an NSAID or predisone.
Side effects may include mouth sores,diarrhea, and nausea dependent on medication and patient. More serious side effects
that may occur.monitored through regular blood and urine tests,include possible liver damage and excessive lowering of white
blood cell count (increasing susceptibility to certain infections) and platelet count (affecting blood clotting). The severity
will dictate the use of certain drugs or a combination of drugs. e.g., HCQ is usually prescribed for
the milder type of disease or when the disease prognosis is unclear to allow some form of joint protection while the course
of disease becomes more certain.
DMARDs are relatively slow acting with a delay of 1-6 months before a clinical respose is evident. Efficacy cannot be
predicted for the individual patient but up to two-thirds of patients may have a response to these agents. Each DMARD has
specific toxicity that requires careful monitoring. From the patient's perspective,the convience of administeration of the
drug,the requirements of the monitoring program, the cost and its monitoring,the time until expected benefit,and the frequency
and potential seriousness of adverse reactions are important considerations. The physician should also assess patient factors
such as compliance and comorbid diseases,the severity and prognosis of the patient's disease and the physician's own confidence,
training experience and knowledge in administeration of the drug.
HCQ tends to cause less toxicity or side effects than other DMARDs but may take anywhere from 3
to 6 months to take effect and even up to 12 months to reach maximum therapeutic value. It also may remain in the body for
as many as 5 years after the last pill is take.In rare cases hydroxychloroquine may damage the mascula, the fine-tuning of
the eye. This condition is very rare and generally occurs at doses higher than those required to treat rheumatoid arthritis.
To reduce toxicity the patient will receive a dose based on the patient's bodyweight. If eye toxicity should occur,the drug
will be discontinued and generally the eye problems will not get worse. HCQ has been known to cause light sensitivity,nausea
and diarrhea in some patients.
Hydroxychloroquine's (Plaquenil) time of action may be 3 to 6 months .Initially,a related drug,chloroquine,was
used,but chloroquine had more side effects. Both fell out of favor for a while. Recent studies have shown HCQ much safer then
chloroquine. The dose of Plaquenil is one or two pills (200 mg) taken taken at bed-time. It is an inexpensive DMARD easily
monitored that works well in early and mild RA. In combination with other DMARDs,plaquenil is useful for more severe types.
Monitoring involves yearly eye examinations.
Methotrexate is the most frequently prescribed DMARD. MTX is highly effective,
once the maximum dose is established. It may cause side effects,including mouth irritation,nausea,diarrhea and vomiting. Methotrexate
also inhibits a person's ability to metabolize and use folic acid,a vitamin that helps stabilize cell growth. Some of the
side effects can be countered by lowering the dose or by taking folic acid,without interfering with MTX's beneficial effects.
Injectable form of methotrexate tends to lower side effects.Because MTX is escreated by the kidneys,it should not be used
by those who are on dialysis or have suffered kidney damage If a patient have mild kidney problems they should consult their
physician. Methotrexate should not be taken with alcohol. Regular laboratory blood monitoring is required.
MTX is normally prescribed at a starting dose of 2 to 4 pills per week (5 to 10 mg). The dose can easily be individualized,with
lower doses for smaller,older patients and higher doses for younger,healthier,larger patients. The starting dose is then increased,
up to 6 to 8 pills per week (1 tablet=2.5 mg) depending upon the course of the disease. Blood tests alert the physician about
side effects About 50 to 80% of patients achieve effective control. Because absorption of the pill varies among
patients, when benefit is incomplete,it may be given by injection. More serious but uncommon problems with MTX include inflammation
and scarring of the liver but most patients who develop this condition have underlying medical conditions that make them susceptible
to this side effect: diabetes,alcoholisim,liver disease,hepatitis,or obesity.
Sulfasalazine: It is most often used in the treatment of milder forms of RA (HCQ included). It
appears to work like MTX--by suppressing parts of the immune system. Because sulfasalazine combines salicylates and sulfa,it
is not recommended for those allergic to sulfa compounds. The medication also causes some side effects,including gastrointestinal
distress,nausea,vomiting,rash and headaches. In rare cases it may affect the white blood cell count. Decreased sperm count
can occur but normilizes when the drug is discontinued. Routine lab monitoring is required.
Sufasalazine is usually taken as a daily dose of 2 to 3 grams. Ideally the dose is increased slowly: 500 mg daily during
week 1;1000 mg daily during week 2; 1500 mg daily during week 3; and 2 grams daily during week 4. Blood tests should be
scheduled monthly for the first 3 months,then every 3 months. SSZ begins working after 4 to 12 weeks
of therapy. It is used more in Europe.
Oral cortisone (predisone) is a steriod that reduces inflammation and swelling.
Predisone may cause side effects such as thinning of bones (osteoporosis). To avoid or lessen side effects,the physician will
administer the lowest possible dose and maintain efficacy. Usually after about six months of taking predisone,most doctors
will slowly try to reduce the dose. In time,predisone may not be necessary. It is often taken with DMARD and NSAID in combination.
Gold salts are not used frequently as in the past. When used gold salts can be taken in pill or
by injection. Side effects such as rash,mouth irritation,kidney problems and diarrhea may occur. Blood and urine are
monitored on a regular basis (every time a patient is injected). Gold normally takes 4 to 6 months to work. The benifits of
gold diminish with time,usually in a time frame somewhere between that of HCQ and MTX. When gold works,the respose is dramatic.
Approximately 30 % of patients taking gold experience side effects. The cost of monitoring is high,and gold causes many adverse
reactions.
Cyclosporine like azathioprine is a type of immunosuppressant that is used
to help prevent the rejection of a transplanted organ. Cyclosporine can cause side effects ranging from excessive hair growth
and elevated blood pressure to more serious problems like kidney dysfunction. It is not recommended for those who already
have high blood pressure or kidney or liver disease. this medication is reserved for those who do not respond to other DMARDs.
Although individual DMARDs are often effective in slowing the progression of rheumatoid arthritis,they may be more effective
when combined. Combinations include the following: MTX and cyclosporine,MTX and anti-TNF therapy,and
MTX combined with HCQ and SSZ (sulfasalazine).Studies comparing DMARD combinations to individual DMARD treatment have
found that they offer increased benefits to patients while not increasing side effects or toxicity. The benefits are especially
evident after one year of treatment,in particular for triple combination therapy.
Corticosteriods(glucocorticoids) are man-made drugs that closely resemble cortisone, a hormone naturally
produced by the adrenal glands in the body. In RA,these drugs are used to treat severe inflammation that is accompanied by
severe pain and stiffness. They are also used to treat systemic RA which may affect the lining of the lungs and blood vessels.
The most common form is predisone. Low dose predisone is usually given to patients,at the start, while the DMARDs take effect
("bridge").
Corticosteriods sometimes are given as injection into one or more joints or other area of inflammation. While eliminating
some side effects,injections may have their own possible problems on the joints,if given more than a few times a year (large
joints) They are very effective and quick-acting for the short term.
Biologics are newer drugs that are becoming available for RA patients that fail to respond to conventional
treatment. The biologic response modifiers-Etanercept (Enbrel) amd Infliximab (Remicade)-
have been available for a couple of years. Both of these agents work,through different ways,to suppress an inflammatory cytokine
called tumour necrosis factor (TNF) Biologics also inhibit the damage to the joint structures that arthritis can cause. For
many people,these drugs have helped when nothing else could.
Despite the benefits of these agents,they have their downside. They must be infused (Remicade) or injected (Enbrel) and
they are expensive ($12,000-$20,000 per annum). Researchers believe that future agents,still in early development stages,may
be less expensive and can be taken orally.
Scientists have identified TNF as one of the naturally occuring hormones that activte cells responsible for the redness,heat,swelling
and pain with joint inflammation. RA patients have an excess of TNF.
Anakinra (Kineret) was approved by the FDA in 11/01 for the treatment of
RA. Anakinra works by blocking the action of another inflammatory cytokine,interleukin-1 which also plays a role in inflammation
and destruction It requires daily injections with a special injecting device.
D2E7, also known as Adalimumab (TNF inhibitor),currently going through phase 111 clinical trials,appears
to be the next biologic compound to be introduced. Ease of administeration is one of the features quoted by the development
team,Abbott Laboratories.
Pain is one symptom virtually everyone will have,regardless of which form of arthritis they have.
For that reason,analgestic (pain-reliever) medications play an important role in the arthritis treatment plan One of the most
commonly used analgestic is acetaminophen, The ACR recommends it as
a first-line option against osteoarthritis pain Unlike NSAIDs acetaminophen and other pure analgestics don't relieve inflammation.
Yet recent studies suggest acetaminophen relieves arthritis pain--even severe pain--as effectively as NSAIDs without NSAID's
risk of GI side effects. At one time acetaminophen was the only analgestic many doctors prescribed for arthritis pain. But
that is changing
A new combination drug called Ultracet,a combination of acetaminophen and tramadol was approved
for acute pain by the FDA in November 2001. Increasingly,doctors are becoming more willing to prescribe narcotic-analgestics--traditionally
reserved for severe,acute pain for their patients with chronic arthritis pain that hasn't responded to more conservative measures.