DRUG TREATMENT OF

GOUT
Prof. Dr. Shah Murad
shahmurad655@yahoo.com

1
2
 GOUT
 also called crystal-induced arthritis, is an
arthritic condition that occurs when uric
acid crystals accumulate in the joints.
 Gout usually affects the large joint of the
big toe, but can also affect other joints,
such as the knee, ankle, foot, hand, wrist
and elbow.
 In rare cases, it may later affect the
shoulders, hips or spine.
 Gout does not spread from joint to joint.
3
 Uric acid is a substance that normally
forms when the body breaks down waste
products (called purines).
 Uric acid is usually dissolved in the blood
and passes through the kidneys into the
urine.
 For people with gout, the uric acid level in
the blood is so high that uric acid crystals
form and deposit in joints and other
tissues. This causes the joint lining to
become inflamed, resulting in sudden and
severe attacks of pain, tenderness,
4
 Afterseveral years, the crystals can build
up in the joints and surrounding tissues,
forming large deposits, called tophi.

 Tophi look like lumps under the skin and

are often found in or near severely
affected joints, on or near the elbow, over
the fingers and toes, and in the outer
edge of the ear. 5
 Anothercondition, called
pseudogout, is caused by deposits of
calcium-based (instead of urate-
based) crystals in the joints.

6
 Although the exact cause is
unknown, gout may be caused
by
 genetic defect in metabolism, which causes
overproduction and retention of uric acid
 kidney impairment that prevents normal
elimination of uric acid
 thiazide diuretic medications (water pills) used
to treat high blood pressure and heart failure
 diseases of the blood cells and blood-forming
organs, certain cancers and psoriasis
 environmental factors, such as obesity, alcohol
abuse and a purine-rich diet. 7
 An episode of gout can be
triggered by:

 drinking too much alcohol

 eating too much of the wrong foods
 surgery
 sudden, severe illness
 crash diets
 injury to a joint
 chemotherapy.

8
 Symptoms of Gout

 Gout generally occurs in four (4)

stages (asymptomatic, acute,
intercritical and chronic) and has the
following signs and symptoms:

(1)Asymptomatic stage - urate

levels rise in the blood, but produces
no symptoms
9
(2) Acute stage - symptoms usually
lasting five to 10 days
 sudden attack of joint pain
 swelling
 joints feel hot, tender and look dusty
red or bruised

10
 Intercriticalstage - symptom-free
intervals between gout episodes.

 Mostpeople have a second attack

from six months to two years, while
others are symptom-free for five to
10 years

11
 (4) Chronic stage

 persistently painful joints with large

urate deposits in the cartilage,
membranes between the bones,
tendons and soft tissues
 skin over the deposits develop sores
and release a white pus
 joint stiffness
 limited motion of affect joint

12
 Diagnosis of Gout

 Thediagnosis of gout is based on

symptoms, blood tests showing high
levels of uric acid, and the finding of
urate crystals in joint fluid.

 Inchronic gout, x-rays show damage

to the cartilage and bones.

13
 MANAGEMENT
 Proper diet
 Avoid or restrict foods high in purine (a
substance that produces uric acid when
broken down).

 These foods include: brains, liver,

kidneys, tripe, sweetbreads, tongue,
shellfish (mussels and oysters), fish roe,
scallops, peas, beans and an excessive
amount of red meat.
 Drink 10 to 12 eight-ounce glasses of
non-alcoholic fluids daily.
14
 Healthy lifestyle
 Reduce alcohol consumption
 Lose weight

15
 Usingmedications for gout can be
complicated, because the treatment
needs to be tailored for each person
and may need to be changed from time
to time.

 Torelieve the pain and swelling of an

acute attack, the doctor may prescribe
nonsteroidal anti-inflammatory drugs
(NSAIDs), colchicine, corticosteroid
drugs, and/or adrenocorticotropic 16
 Toprevent future attacks, the doctor may
recommend colchicine, probenecid
(Benemid, Parbenem or Probalan),
sulfinpyrazone (Anturane), or allopurinol
(Lopurin, Zurinol or Zyloprim).

 Toprevent or treat tophi, probenecid,

sulfinpyrazone and allopurinol are
recommended.
17
 SPECIFIC DRUGS for Gout
 non-steroidal anti-inflammatory
drugs (NSAIDS)
 colchicine
 corticosteroids
 adrenocorticotropic hormone (ACTH)
 allopurinol
 probenecid
 sulfinpyrazone

18
Colchicine

19
 COLCHICINE
 It is used to treat acute flares of gouty arthritis
and to prevent recurrent acute attacks.

 Colchicine does not cure gout or take the place

of other medicines that lower the amount of
uric acid in the body.
 It prevents or relieves gout attacks by reducing
inflammation.
 Colchicine may be used in 2 ways: some people
take small amounts of it regularly for months or
years, while others take large amounts of
colchicine during a short period of time (several
20
 Colchicine, an alkaloid is identified as
a tricyclic alkaloid, and it has pain-
relieving and anti-inflammatory
effects for gout which are linked to
its ability to bind with tubulin.

21
 Colchicineinhibits microtubule
polymerization by binding to tubulin,
one of the main constituents of
microtubules.

 Availabilityof tubulin is essential to

mitosis, and therefore colchicine
effectively functions as a "mitotic
poison" or spindle poison
22
 colchicinealso inhibits neutrophil
motility and activity, leading to a net
anti-inflammatory effect.

 Colchicine also inhibits uric acid (urate)

crystal deposition, which is enhanced
by a low pH in the tissues, probably by
inhibiting oxidation of glucose and
subsequent lactic acid production in
leukocytes.
 The inhibition of uric acid crystals is a
vital aspect on the mechanism of gout
23
 Pharmaceutical companies have
developed a combination therapy to
treat constipation-predominant
irritable bowel syndrome which
combines colchicine with the anti-
inflammatory drug olsalazine.

24
 Long term (prophylactic) regimens of oral
colchicine are absolutely contraindicated
in patients with advanced renal failure
(including those on dialysis).
 10-20% of a colchicine dose is excreted
unchanged by the kidneys.
 Colchicine is not removed by
hemodialysis.
 Cumulative toxicity is a high probability in
this clinical setting. A severe
neuromyopathy may result. The
presentation includes a progressive onset
of proximal weakness, elevated creatine 25
 Colchicinetoxicity can be potentiated by
the concomitant use of cholesterol
lowering drugs (statins, fibrates).

 Thisneuromuscular condition can be

irreversible (even after drug
discontinuation).

 Accompanying dementia has been noted

in advanced cases.
26
 Other Side effects include gastro-
intestinal upset and neutropenia.

 High doses can also damage

bone marrow and lead to anemia.
 Note that all of these side
effects can result from hyper-
inhibition of mitosis

27
 Toxicity
 Colchicine poisoning has been compared to
arsenic poisoning: symptoms start 2 to 5 hours
after the toxic dose has been ingested and
include burning in the mouth and throat, fever,
vomiting, diarrhea, abdominal pain and
kidney failure.

 These symptoms may set in as many as 24

hours after the exposure. Onset of multiple-
system organ failure may occur within 24 to 72
hours. This includes hypovolemic shock due to
extreme vascular damage and fluid loss
through the GI tract, which may result in death.
28
 Additionally,sufferers may experience
kidney damage resulting in low urine
output and bloody urine; low white blood
cell counts (persisting for several days);
anemia; muscular weakness; and
respiratory failure.

 Recovery may begin within 6 to 8 days.

There is no specific antidote for
colchicine, although various treatments
do exist 29
30