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DRUG TREATMENT OF DRUG TREATMENT OF GOUTGOUT

Prof. Dr. Shah MuradProf. Dr. Shah Murad

shahmurad655@yahoo.comshahmurad655@yahoo.com

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GOUTGOUT also called crystal-induced also called crystal-induced arthritisarthritis, is an , is an

arthritic condition that occurs when uric arthritic condition that occurs when uric acid crystals accumulate in the joints. acid crystals accumulate in the joints.

Gout usually affects the large joint of the Gout usually affects the large joint of the big toe, but can also affect other joints, big toe, but can also affect other joints, such as the knee, ankle, foot, hand, wrist such as the knee, ankle, foot, hand, wrist and elbow.and elbow.

In rare cases, it may later affect the In rare cases, it may later affect the shoulders, hips or spine. shoulders, hips or spine.

Gout does not spread from joint to joint. Gout does not spread from joint to joint.

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Uric acidUric acid is a substance that normally forms is a substance that normally forms when the body breaks down waste products when the body breaks down waste products (called purines). (called purines).

Uric acid is usually dissolved in the blood and Uric acid is usually dissolved in the blood and passes through the kidneys into the urine. passes through the kidneys into the urine.

For people with For people with goutgout, the uric acid level in , the uric acid level in the blood is so high that uric acid crystals the blood is so high that uric acid crystals form and deposit in joints and other tissues. form and deposit in joints and other tissues. This causes the joint lining to become This causes the joint lining to become inflamed, resulting in sudden and severe inflamed, resulting in sudden and severe attacks of pain, tenderness, redness and attacks of pain, tenderness, redness and warmth. warmth.

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After several years, the crystals can build After several years, the crystals can build up in the joints and surrounding tissues, up in the joints and surrounding tissues, forming large deposits, called tophi. forming large deposits, called tophi.

Tophi look like lumps under the skin and Tophi look like lumps under the skin and are often found in or near severely are often found in or near severely affected joints, on or near the elbow, over affected joints, on or near the elbow, over the fingers and toes, and in the outer the fingers and toes, and in the outer edge of the ear. edge of the ear.

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

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Although the exact cause is Although the exact cause is unknown, gout may be caused unknown, gout may be caused

byby

genetic defect in metabolism, which causes genetic defect in metabolism, which causes overproduction and retention of uric acid overproduction and retention of uric acid

kidney impairment that prevents normal kidney impairment that prevents normal elimination of uric acid elimination of uric acid

thiazide diuretic medications (water pills) used thiazide diuretic medications (water pills) used to treat high blood pressure and heart failure to treat high blood pressure and heart failure

diseases of the blood cells and blood-forming diseases of the blood cells and blood-forming organs, certain cancers and organs, certain cancers and psoriasispsoriasis

environmental factors, such as environmental factors, such as obesityobesity, alcohol , alcohol abuse and a purine-rich diet. abuse and a purine-rich diet.

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An episode of gout can be An episode of gout can be triggered by:triggered by:

drinking too much alcohol drinking too much alcohol eating too much of the wrong foods eating too much of the wrong foods surgery surgery sudden, severe illness sudden, severe illness crash diets crash diets injury to a joint injury to a joint chemotherapychemotherapy. .

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Symptoms of GoutSymptoms of Gout

GoutGout generally occurs in four (4) stages generally occurs in four (4) stages (asymptomatic, acute, intercritical and (asymptomatic, acute, intercritical and chronic) and has the following signs and chronic) and has the following signs and symptoms: symptoms:

(1)Asymptomatic stage(1)Asymptomatic stage - urate levels - urate levels rise in the blood, but produces no rise in the blood, but produces no symptoms symptoms

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(2) Acute stage(2) Acute stage - symptoms usually - symptoms usually lasting five to 10 days lasting five to 10 days

sudden attack of joint pain sudden attack of joint pain swelling swelling joints feel hot, tender and look dusty joints feel hot, tender and look dusty

red or bruised red or bruised

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Intercritical stageIntercritical stage - symptom-free - symptom-free intervals between gout episodes. intervals between gout episodes.

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

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(4) Chronic stage(4) Chronic stage

persistently painful joints with large persistently painful joints with large urate deposits in the cartilage, urate deposits in the cartilage, membranes between the bones, membranes between the bones, tendons and soft tissues tendons and soft tissues

skin over the deposits develop sores skin over the deposits develop sores and release a white pus and release a white pus

joint stiffness joint stiffness limited motion of affect joint limited motion of affect joint

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Diagnosis of GoutDiagnosis of Gout

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

In chronic gout, x-rays show damage In chronic gout, x-rays show damage to the cartilage and bones. to the cartilage and bones.

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MANAGEMENTMANAGEMENT Proper dietProper diet Avoid or restrict foods high in purine (a Avoid or restrict foods high in purine (a

substance that produces uric acid when substance that produces uric acid when broken down). broken down).

These foods include: brains, liver, These foods include: brains, liver, kidneys, tripe, sweetbreads, tongue, kidneys, tripe, sweetbreads, tongue, shellfish (mussels and oysters), fish roe, shellfish (mussels and oysters), fish roe, scallops, peas, beans and an excessive scallops, peas, beans and an excessive amount of red meat. amount of red meat.

Drink 10 to 12 eight-ounce glasses of Drink 10 to 12 eight-ounce glasses of non-alcoholic fluids daily. non-alcoholic fluids daily.

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Healthy lifestyleHealthy lifestyle Reduce alcohol consumption Reduce alcohol consumption Lose weight Lose weight

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

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

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

To To prevent or treat tophiprevent or treat tophi, probenecid, , probenecid, sulfinpyrazone and allopurinol are sulfinpyrazone and allopurinol are recommended. recommended.

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SPECIFIC DRUGS for GoutSPECIFIC DRUGS for Gout

non-steroidal anti-inflammatory non-steroidal anti-inflammatory drugs (NSAIDS) drugs (NSAIDS)

colchicine colchicine corticosteroids corticosteroids adrenocorticotropic hormone (ACTH) adrenocorticotropic hormone (ACTH) allopurinol allopurinol probenecid probenecid sulfinpyrazonesulfinpyrazone

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ColchicineColchicine

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COLCHICINECOLCHICINE It is used to treat acute flares of gouty arthritis It is used to treat acute flares of gouty arthritis

and to prevent recurrent acute attacks. and to prevent recurrent acute attacks.

Colchicine does not cure gout or take the place Colchicine does not cure gout or take the place of other medicines that lower the amount of uric of other medicines that lower the amount of uric acid in the body. acid in the body.

It prevents or relieves gout attacks by reducing It prevents or relieves gout attacks by reducing inflammation. inflammation.

Colchicine may be used in 2 ways: some people Colchicine may be used in 2 ways: some people take small amounts of it regularly for months or take small amounts of it regularly for months or years, while others take large amounts of years, while others take large amounts of colchicine during a short period of time (several colchicine during a short period of time (several hours). hours).

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Colchicine, an alkaloid is identified as Colchicine, an alkaloid is identified as a tricyclic alkaloid, and it has pain-a tricyclic alkaloid, and it has pain-relieving and relieving and anti-inflammatoryanti-inflammatory effects for gout which are linked to effects for gout which are linked to its ability to bind with its ability to bind with tubulintubulin. .

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Colchicine inhibits microtubule Colchicine inhibits microtubule polymerization by binding to polymerization by binding to tubulintubulin, , one of the main constituents of one of the main constituents of microtubulesmicrotubules. .

Availability of tubulin is essential to Availability of tubulin is essential to mitosismitosis, and therefore colchicine , and therefore colchicine effectively functions as a "mitotic effectively functions as a "mitotic poison" or poison" or spindle poisonspindle poison

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colchicine also inhibits colchicine also inhibits neutrophilneutrophil motility and activity, leading to a net motility and activity, leading to a net anti-inflammatoryanti-inflammatory effect. effect.

Colchicine also inhibits Colchicine also inhibits uric aciduric acid ( (urateurate) ) crystal deposition, which is enhanced by crystal deposition, which is enhanced by a low pH in the tissues, probably by a low pH in the tissues, probably by inhibiting oxidation of inhibiting oxidation of glucoseglucose and and subsequent subsequent lactic acidlactic acid production in production in leukocytes. leukocytes.

The inhibition of uric acid crystals is a The inhibition of uric acid crystals is a vital aspect on the mechanism of gout vital aspect on the mechanism of gout treatment. treatment.

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Pharmaceutical companies have Pharmaceutical companies have developed a combination therapy to developed a combination therapy to treat constipation-predominant treat constipation-predominant irritable bowel syndromeirritable bowel syndrome which which combines colchicine with the anti-combines colchicine with the anti-inflammatory drug inflammatory drug olsalazineolsalazine..

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Long term (prophylactic) regimens of oral Long term (prophylactic) regimens of oral colchicine are absolutely contraindicated colchicine are absolutely contraindicated in patients with advanced renal failure in patients with advanced renal failure (including those on dialysis).(including those on dialysis).

10-20% of a colchicine dose is excreted 10-20% of a colchicine dose is excreted unchanged by the kidneys. unchanged by the kidneys.

Colchicine is not removed by hemodialysis. Colchicine is not removed by hemodialysis. Cumulative toxicity is a high probability in Cumulative toxicity is a high probability in

this clinical setting. A severe this clinical setting. A severe neuromyopathy may result. The neuromyopathy may result. The presentation includes a progressive onset presentation includes a progressive onset of proximal weakness, elevated creatine of proximal weakness, elevated creatine kinase, and sensorimotor polyneuropathy. kinase, and sensorimotor polyneuropathy.

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

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

Accompanying dementia has been noted Accompanying dementia has been noted in advanced cases. in advanced cases.

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Other Side effects include gastro-Other Side effects include gastro-intestinal upset and intestinal upset and neutropenianeutropenia. .

High doses can also damage High doses can also damage bone marrowbone marrow and lead to and lead to anemiaanemia. .

Note that all of these side effects Note that all of these side effects can result from hyper-inhibition can result from hyper-inhibition of mitosis of mitosis

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ToxicityToxicity Colchicine poisoning has been compared to Colchicine poisoning has been compared to

arsenicarsenic poisoning: symptoms start 2 to 5 hours poisoning: symptoms start 2 to 5 hours after the toxic dose has been ingested and after the toxic dose has been ingested and include burning in the mouth and throat, include burning in the mouth and throat, feverfever, , vomiting, diarrhea, abdominal pain and kidney vomiting, diarrhea, abdominal pain and kidney failure. failure.

These symptoms may set in as many as 24 These symptoms may set in as many as 24 hours after the exposure. Onset of multiple-hours after the exposure. Onset of multiple-system organ failure may occur within 24 to 72 system organ failure may occur within 24 to 72 hours. This includes hypovolemic shock due to hours. This includes hypovolemic shock due to extreme vascular damage and fluid loss extreme vascular damage and fluid loss through the GI tract, which may result in death. through the GI tract, which may result in death.

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Additionally, sufferers may experience Additionally, sufferers may experience kidney damage resulting in low urine kidney damage resulting in low urine output and bloody urine; low white blood output and bloody urine; low white blood cell counts (persisting for several days); cell counts (persisting for several days); anemia; muscular weakness; and anemia; muscular weakness; and respiratory failure. respiratory failure.

Recovery may begin within 6 to 8 days. Recovery may begin within 6 to 8 days. There is no specific antidote for There is no specific antidote for colchicine, although various treatments colchicine, although various treatments do existdo exist

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