| WHAT
ARE THE SPECIFIC DRUGS USED FOR PSEUDOGOUT?
Nonsteroidal
Anti-Inflammatory Drugs (NSAIDs)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
block prostaglandins, the substances that
dilate blood vessels and cause inflammation
and pain. They are the drugs of choice for
young, healthy adults without any other serious
medical condition. NSAIDs are usually taken
orally at their highest safe dosage as long
as gout symptoms persist and for three or
four days after. Low doses of NSAIDs may be
used to prevent gout attacks, including in
patients who are starting anti-hyperuricemic
therapies.
NSAIDs
Used. Indomethacin (Indocin)
in doses up to 200 mg a day is the usual choice
for gout. The first dose of indomethacin usually
begins to act against the pain and inflammation
within 24 hours and often much sooner. Ibuprofen,
naproxen, sulindac, or others are good alternatives
particularly for elderly patients who might
experience confusion or bizarre sensations
with indomethacin. Aspirin is an NSAID, but
is associated with a higher risk for gout
and should be avoided. There are dozens of
NSAIDs available. [S ee Box Ulcers and Gastrointestinal
Bleeding, for a list of NSAIDs].
Side
Effects and Complications. Regular
use of even over-the-counter NSAIDs may be
hazardous for anyone and has been are associated
with the following side effects:
Ulcers
and gastrointestinal bleeding. This is the
major danger with long-term use of NSAIDs.
[ See Box Ulcers and Gastrointestinal Bleeding.]
Increased
blood pressure. This is a particular problem
in those on medications to reduce hypertension.
Piroxicam (Feldene), naproxen (Aleve), and
indomethacin (Indocin) appear to pose the
greatest risks for high blood pressure. (Sulindac
has the smallest effect.) People with hypertension,
severe vascular disease, kidney, or liver
problems, and those taking diuretics must
be closely monitored if they need to take
NSAIDs.
- Dizziness, ringing
in the ear.
- Headache.
- Skin rash.
- Depression has
also been noted.
- Confusion or
bizarre sensation (in some higher-potency
NSAIDs, such as indomethacin).
- Kidney abnormalities
have been reported in people taking NSAIDs,
which resolves when the drugs are withdrawn.
Any sudden weight gain or swelling should
be reported to a physician.
- Diabetics taking
oral hypoglycemics may need to adjust
the dosage if they also need to take NSAIDs
because of possible harmful interactions
between the drugs.
Ulcers and Gastrointestinal Bleeding
- NSAIDs are a
major cause of ulcers and gastrointestinal
(GI) bleeding. Gastrointestinal complications
from the use of NSAIDs account for almost
100,000 hospitalizations and at least
16,000 deaths a year in the United States.
Bleeding and ulcers can occur at any time,
with or without symptoms. One study indicated
that taking NSAIDs for only six months
posed a risk for symptomatic ulcers that
was greater than 1%. The risk for bleeding
is continuous as long as a patient is
on these drugs and may even persist as
long as a year after the drug is discontinued.
Alcohol abuse may increase the risks for
GI bleeding when taking NSAIDs. Because
NSAIDs reduce the clotting of the blood,
anyone undergoing surgery should stop
taking the medication a week before the
operation.
Ulcer Risk for Specific NSAIDs. One study
ranked the sixteen most commonly used
NSAIDs according to risk for ulcers and
bleeding.
- Lowest Risk:
nabumetone (Relafen), etodolac (Lodine),
salsalate, and sulindac (Clinoril).
- Medium risk:
diclofenac (Voltaren), ibuprofen (Motrin,
Advil, Nuprin, Rufen), aspirin, naproxen
(Aleve, Naprosyn, Naprelan, Anaprox),
and tolmetin (Tolectin). Drugs within
this group vary in risk. Studies show,
for example, that short-term use of naproxen
is twice as likely as ibuprofen to be
associated with hospitalization from GI
bleeding. Although ketoprofen (Actron,
Orudis KT) was considered a medium-risk
drug, another study reported that even
one week of taking the drug at low doses
causes significant GI injury.
Highest risk: flurbiprofen (Ansaid), piroxicam
(Feldene), fenoprofen, indomethacin (Indocin),
meclofenamate (Meclomen), and oxaprozin.
Drugs for Prevention of NSAID-Induced
Ulcers. For people who need to take NSAIDs
regularly, some agents are available that
may protect against bleeding and ulcers.
- Proton-pump
inhibitors a include omeprazole (Prilosec),
lansoprazole (Prevacid), rabeprazole (Aciphex),
and pantoprozole. Proton pump inhibitors
are possibly the most protective agents
and can actually heal existing ulcers.
Their use has been demonstrated to reduce
NSAID-ulcer rates by as much as 80% compared
with no treatment.
- Misoprostol.
Misoprostol is a prostaglandin, the protective
substance blocked by NSAID use. It protects
against the major intestinal toxicity
of NSAIDs. It is used to prevent NSAID-induced
ulcers, both duodenal and gastric, but
is not useful in healing existing ulcers.
- H2 Blockers.
Some H2 blockers may help prevent NSAID-induced
ulcers. These drug are available over
the counter and include famotidine (Pepcid
AC), ranitidine (Zantac), cimetidine (Tagamet),
and nizatidine (Axid). In one 2000 study,
ranitidine and famotidine, were associated
with a lower risk for bleeding in patients
taking NSAIDs, while another study found
no protection from cimetidine.
COX-2
Inhibitors
Celecoxib (Celebrex), rofecoxib (Vioxx), and
meloxicam (Mobic) are known as COX-2 (cyclooxygenase-2)
inhibitors, the so-called super-aspirins.
These agents may prove to be as effective
and less harmful to the GI tract than NSAIDs.
Theoretically, they may even have properties
that produce less adverse effects on cartilage
than NSAIDs may have. They may be effective
for gout, although there is no data on the
use of these agents for gout patients as yet.
Some studies
have found that patients taking COX-2 inhibitors
have the same gastrointestinal symptoms (eg,
diarrhea, abdominal discomfort) as standard
NSAIDs. (Other side effects found with short-term
use include headache, and dizziness.) Importantly,
however two 2000 studies reported a lower
incidence of ulcers and other toxic side effects
in patients taking the COX-2 inhibitors than
in those taking NSAIDs. The drugs were all
equally effective in relieving pain. (One
study compared celecoxib with the NSAIDs ibuprofen
or diclofenac and the other compared rofecoxib
with the NSAID naproxen). One 1999 study even
found the rate of GI problems with celecoxib
was equal to that in people who do not take
NSAIDs at all. COX-2 inhibitors are currently
more expensive than traditional NSAIDs, however,
and some insurers do not pay for them.
Possible Negative Effects. In spite of their
promise, some researchers theorize that inhibiting
COX-2 may have some negative side effects
over the long term:
- One 2000 study observed that the COX-2
inhibitors had some adverse effects on
kidney function, particularly in elderly
people, that were similar to the effects
of standard NSAIDs.
- Patients taking anticoagulant drugs
may experience a higher risk for bleeding
with the use of these agents.
- A few cases of psychiatric side effects
(hallucinations), fluid build up, high
blood pressure, and excess potassium in
the blood has been observed with higher
doses of celecoxib or rofecoxib.
- They may have negative effects on pregnancy
and fertility.
More research is needed to
confirm or refute any possible hazard.
Other Investigative Alternatives
to NSAIDs
NO-NSAIDS. Experimental agents are being developed
that combine nitric oxide with NSAIDs (NO-NSAIDs).
Nitric oxide increases blood flow in the mucous
lining and secretions of mucus and bicarbonate.
Combining nitric oxide with NSAIDs may provide
benefits similar to the COX-2 inhibitors.
Arthrotec. Arthrotec is a combination of misoprostol
and the NSAID diclofenac that may reduce the
risk for gastrointestinal bleeding. One study
found that patients taking Arthrotec had 65%
to 80% fewer ulcers than those who took NSAIDs
alone.
Colchicine
Colchicine, a derivative of the autumn crocus
(also called the meadow saffron), has been
used against gout attacks for centuries. It
is highly effective though no longer the first
drug of choice because of its frequent, unpleasant,
and sometimes very serious side effects. The
drug is generally not appropriate for elderly
patients or those with kidney, liver, or bone
marrow disorders. It can also effect fertility.
Oral Regimen. The oral regimen
requires doses every hour until the symptoms
either improve or side effects develop; improvement
should be evident by the tenth dose. Oral
colchicine usually eliminates the pain of
an acute attack within 48 hours. It is unsuitable
for many patients, however, because of nausea,
vomiting, diarrhea, or abdominal cramps, which
occur at the high doses necessary to relieve
symptoms. Low doses are helpful for preventing
further attacks, including in patients who
are starting anti-hyperuricemic therapies.
Low doses do not pose as high a risk for GI
symptoms. (Taking low doses for a long duration,
however, may suppress bone marrow function
and cause some nerve and muscular injury in
certain people.)
Note. The antibiotic erythromycin
or H2 blockers, such as famotidine (Pepcid
AC), cimetidine (Tagamet), ranitidine (Zantac),
may intensify the gastrointestinal side effects
of colchicine.
Intravenous. Intravenous administration of
colchicine relieves episodes of gout without
gastrointestinal effects and for a time, physicians
hoped it could be used routinely. The intravenous
route has some serious side effects, however,
and poses an increased risk for injury to
the kidney, liver, central nervous system,
and bone marrow.
Warning Note: Overdose of Colchicine can be
fatal, and there have even been reports of
fatalities with low doses.
Corticosteroids
Corticosteroids, known commonly as steroids,
are used when patients cannot tolerate other
anti-inflammatory drugs or they prove ineffective
for an attack of gout. They are becoming popular
in elderly people. Corticotropin (ACTH), a
drug that converts to a steroid, is another
option. Corticosteroids can be administered
in different forms:
- If only one joint is affected, an injection
of the steroid triamcinolone directly
into the affected joint can often bring
rapid pain relief.
- A single muscular injection of ACTH
or triamcinolone may be the most rapid
and reliable method for terminating an
attack. Oral doses of prednisone are usually
given for seven to 10 days after the injection
in tapered doses. This is to prevent a
rebound attack, which can occur after
the injection.
* Adopted from MD Consult Patient Handouts
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