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Gout
Hyperuricemia
嘉義長庚紀念醫院嘉義長庚紀念醫院嘉義長庚紀念醫院嘉義長庚紀念醫院報告人報告人報告人報告人：：：：楊雅涵楊雅涵楊雅涵楊雅涵 實習生實習生實習生實習生指導藥師指導藥師指導藥師指導藥師：：：：蔡騰輝蔡騰輝蔡騰輝蔡騰輝 藥師藥師藥師藥師報告日期報告日期報告日期報告日期：：：：2016/03/092016/03/092016/03/092016/03/09
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Outline• Definition• Pathophysiology• Epidemiology• Clinical features• Risk factor• Diagnosis• Treatment• Acute gout• Chronic gout (Hyperuricemia)
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Definition�Gout is a metabolic disease �Deposition of monosodium
urate (MSU) crystals� It can develop chronic
tophaceous gout and hyperuricemia.
� MSU crystals have deposited in soft tissues and are most commonly found in the toes,fingers,and elbows.
Ref: Applied therapeutics 10th 2013
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http://www.medicinenet.com/gout_pictures_slideshow/article.htm
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http://www.medicinenet.com/gout_pictures_slideshow/ article.htm
“Needle-Shaped” monosodium urate crystals
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Pathophysiology
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Purine Catabolism
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Purines are degraded to uric acid in human beings.
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Uric Acid Disposition • end product of purine
nucleotide (nucleoprotein) metabolism in all cells of the body.
• no biological function• Humans lack the enzyme
uricase• Uric acid is not metabolized
in humans and primarily is excreted renally
Ref: Applied therapeutics 10th 2013
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Hyperuricemia�excessive urate production �diminished renal uric acid excretion.�Serum urate concentration > 7 mg/dL is called
“Hyperuricemia”.�Persistent hyperuricemia can be divided into two
categories:-Primary hyperuricemia-Secondary hyperuricemia
�Hyperuricemia appropriate to the non-crystal deposition .
Ref: UpToDate-Asymptomatic hyperuricemia
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Hyperuricemia• Overproduction
The body makes too much uric acid (10%)
• UnderexcretionDefect in the renal clearance (90%)
Ref: Applied therapeutics 10th 2013
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Ref: Clinical Features and Treatment of GoutCHRISTOPHER M. BURNS • ROBERT L. WORTMANN
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Ref: Clinical Features and Treatment of GoutCHRISTOPHER M. BURNS • ROBERT L. WORTMANN
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HPRT：：：：hypoxanthine-guanine phosphoribosyl transferasePRPP ：：：：5’-phosphoribosyl-1-pyrophosphate synthetase
the key determinant of purine synthesis and uric ac id product
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Ref:Gout-2007
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Epidemiology
The risk of gouty arthritis: Men=Women• More men are hyperuricemic.• Men are six times more likely than women to have SUA
concentrations >7 mg/dL.• Gout occurs as often in postmenopausal elderly women as in
men.• The average age at the time of the first attack was 48 years.
Ref: Applied therapeutics 10th 2013
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擷取自yahoo奇摩新聞
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Clinical Features-Gout
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Ref:https://www.outwithgout.ca/WhatIsGout/Progression
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Asymptomatic hyperuricemia• Asymptomatic hyperuricemia is a condition in
which the serum urate level is high, but gout has not yet occurred
• The phase of asymptomatic hyperuricemia ends with the first attack of gouty arthritis or urolithiasis.
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Acute gouty arthritis• The first attack of acute gouty arthritis usually
occurs between age 40 and 60 years in men and after age 60 in women
• A single joint is involved in about 85% to 90% of first attacks, with the first metatarsophalangeal joint being the most commonly affected site.
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Acute gouty arthritis• The initial attack occurs with explosive
suddenness and commonly begins at night after the individual has gone to sleep feeling well.
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Intercritical gout• It been applied to the periods between gouty
attacks.
• Most patients suffer a second attack within 6 months to 2 years.
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Chronic gouty arthritis• Tophaceous gout is the consequence of the
chronic inability to eliminate urate as rapidly as it is produced.
• As the urate pool expands, deposits of urate crystals appear in cartilage, synovial membranes, tendons, soft tissues, and elsewhere.
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Chronic gouty arthritis
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Ref:2015 Gout Classification Criteria: An American College of Rheumatology/European League Against Rhe umatism Collaborative Initiative
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Clinical Features-Gout
• Pain• Number and Type of Joints • Nocturnal Occurrence• Physical Stress
Ref: Applied therapeutics 10th 2013
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Risk factors• Obesity• Hypertension• Hyperlipidemia• Diabetes• Renal insufficiency• Drugs • Purine-rich foods
Ref: Applied therapeutics 10th 2013
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Diagnosis• Laboratory Tests• Radiography• Joint Fluid Aspiration
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2015 Gout Classification Criteria An American Colle ge of Rheumatology/European League Against Rheumatism Collaborative Initiative
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Criteria for Diagnosis
American College of Rheumatology (ACR) 1977
• at least six criteria are needed for diagnosis unlessMSU crystals arepresent in joint fluid aspirate
Ref: Applied therapeutics 10th 2013
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2015 Gout Classification Criteria
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Criteria for Diagnosis-Gout
European League Against Rheumatism (EULAR) 2006
Ref: Applied therapeutics 10th 2013
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Ref: Applied therapeutics 10th 2013
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Asymptomatic hyperuricemia• large percentage of hyperuricemic patients may
never experience an acute attack of gout.
• treated easily within 48 to 72 hours,and if the patient has at least two attacks in a year ULT can then be considered.
• Hyperuricemia may represent an important risk factor for the development of CHD.
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Treatment- Acute GoutGoals of Therapy• relieve pain and inflammation.
Management guidelines� EULAR Guidelines
� BSR/BHPR (British Society of Rheumatology and British Health Professionals in Rheumatology) Guidelines
Ref: Applied therapeutics 10th 2013
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Management guidelines: EULAR Guidelines V.S BSR/BHPR Guidelines
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Treatment- Acute Gout
Ref: Applied therapeutics 10th 2013
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Treatment of Acute Gout
Ref: UpToDate 2013
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Treatment- Acute GoutNSAID-nonselective• first-line therapy• SE: GI bleeding and/or ulceration and inhibition of
platelet aggregation• Ibuprofen is the least likely to cause GI adverse
effects and is perhaps the safest nonselective NSAID.
Ref: Applied therapeutics 10th 2013
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Treatment- Acute GoutNSAID-COX-2 selective
• SE:increased cardiovascular risks• Etoricoxib approved for the treatment of acute gouty
arthritis.• Celecoxib -an appropriate option for the treatment of
gout in patients with bleeding risks.
• Do not inhibit platelets at normal doses.
Ref: Applied therapeutics 10th 2013
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Treatment- Acute Gout
Colchicine• Inhibit cytokines and chemokines.
• 1.2 mg to start followed by 0.6 mg in 1 hour• not exceed 6 mg/gout• should be used cautiously in pt’s with Clcr< 30 mL/min
and taking other drugs that inhibit either CYP3A4 or P-glycoprotein .
Ref: Applied therapeutics 10th 2013
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Treatment- Acute GoutCorticosteroids
• Oral Prednisone 20-40 mg/day• acute gout episode involves only one or two joints,
intra-articular corticosteroid administration could minimize adverse effects
• potential for rebound pain when abruptly discontinued
Ref: Applied therapeutics 10th 2013
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Treatment Acute Gout Opiate Analgesics• occasional patient requires more pain control• narcotic analgesic can be a reasonable adjunct
to blunt the pain of acute gouty arthritis
Ref: Applied therapeutics 10th 2013
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Treatment- Acute GoutNonpharmacologic intervention
• Ice• Alcohol consumption• Diet modification• Delay of hypouricemic therapy
Ref: Applied therapeutics 10th 2013pictures :google
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Treatment- Chronic Gout
Goals of Therapy• Lowering serum concentrations of uric acid
• The SUA concentration should be decreased to < 6 mg/dL , which is below the saturation point for monosodium urate.
Ref: Applied therapeutics 10th 2013
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Drug Therapy of Hyperuricemia
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Xanthine Oxidase Inhibitors
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Allopurinol
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Xanthine Oxidase Inhibitors
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Uricosuric agentsProbenecid• Average Dose：250 mg BID for the first week, increasing
to 500 mg BID starting the second week, maximum 3 g daily.
• Concerns：Avoid in patients with chronic kidney disease or a history of renal stones
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Uricosuric agentsSulfinpyrazone• Average Dose：50 mg twice daily, titrated to 300–400
mg/day
• Concerns ：Useful in urate underexcretion. Avoid in patients with history of urolithiasis.
• Low doses → inhibits the tubular secretion of uric acid • Usual therapeutic doses → inhibits the tubular
reabsorption of uric acid
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Uricosuric agentsBenzbromarone• Average Dose：50-100 mg/d, maximum 150 mg
daily.
• Concerns ：Avoid in patients with history of urolithiasis and or a history of renal stones.
• hepatotoxicity
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UricasesRasburicase(Fasturtec )® 1 5mg/vial • Average Dose：0.2 mg/kg/dose IV• Concerns： G6PD deficiency, anaphylactic, hemolytic
reactions
Pegloticase • Average Dose：8 mg IV infusion for 2hrs every 2 weeks • Concerns： G6PD deficiency
• approved by the FDA in 2010.
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Comorbid Conditions• DYSLIPIDEMIA
-a fibrate would be preferred over niacin
-Fenofibrate has been shown to decrease SUA cons. and modestly increases renal urate excretion.
• HYPERTENSION-Losartan appears to increase renal excretion of uric acid
• Concurrent daily Losartan 100 mg and Fenofibrate 300 mg decreased SUA cons by a mean of about 1mg/dL.
Ref: Applied therapeutics 10th 2013
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References• Applied therapeutics 10th 2013• UpToDate-Asymptomatic hyperuricemia• Clinical Features and Treatment of Gout-CHRISTOPHER
M. BURNS • ROBERT L. WORTMANN• 2015 Gout Classification Criteria• 台灣痛風與高尿酸血症診療指引
• https://www.cgmh.org.tw/stor/drug001.aspx嘉義長庚醫院藥品查詢系統
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Thank You for your attention
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