Drug Treatment Of Gout

DRUG TREATMENT OF GOUT Prof. Dr. Shah Murad [email protected]

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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

 After

several 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

 Another

condition, called pseudogout, is caused by deposits of calcium-based (instead of uratebased) crystals in the joints.

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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 7 abuse and a purine-rich diet.

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

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 Intercritical

stage - symptom-free intervals between gout episodes.

 Most

people have a second attack from six months to two years, while others are symptom-free for five to 10 years

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(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  The

diagnosis of gout is based on symptoms, blood tests showing high levels of uric acid, and the finding of urate crystals in joint fluid.

 In

chronic 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

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 Using

medications 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.

 To

relieve the pain and swelling of an acute attack, the doctor may prescribe nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, corticosteroid drugs, and/or adrenocorticotropic 16

 To

prevent future attacks, the doctor may recommend colchicine, probenecid (Benemid, Parbenem or Probalan), sulfinpyrazone (Anturane), or allopurinol (Lopurin, Zurinol or Zyloprim).

 To

prevent 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

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COLCHICINE

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

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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

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 Colchicine,

an alkaloid is identified as a tricyclic alkaloid, and it has painrelieving and anti-inflammatory effects for gout which are linked to its ability to bind with tubulin.

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 Colchicine

inhibits microtubule polymerization by binding to tubulin, one of the main constituents of microtubules.

 Availability

of tubulin is essential to mitosis, and therefore colchicine effectively functions as a "mitotic poison" or spindle poison 22

 colchicine

also 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 antiinflammatory drug olsalazine.

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 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

 Colchicine

toxicity can be potentiated by the concomitant use of cholesterol lowering drugs (statins, fibrates).

 This

neuromuscular condition can be irreversible (even after drug discontinuation).

 Accompanying

dementia has been noted in advanced cases. 26

 Other

Side effects include gastrointestinal upset and neutropenia.

 High

doses can also damage bone marrow and lead to anemia.  Note that all of these side effects can result from hyperinhibition 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.

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These symptoms may set in as many as 24 hours after the exposure. Onset of multiplesystem 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

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