Pharmacotherapy in Gout and Osteoarthritis Thitima Doungngern, PharmD, MPharm, BCPS Faculty of Pharmaceutical Sciences Prince of Songkla University การประชุมวิชาการ วิทยาลัยเภส ั ชบําบัดแห่งประเทศไทย เรื=อง Contemporary Review in Pharmacotherapy 2013 วันที= 17 มกราคม พ.ศ.2556 Outline: Uric acid pathway Gout vs. hyperuricemia How to manage acute gout attack? Gout gout attack? Chronic management of gout Hyperuricemia - Who should be treated? Purine synthesis 300-600 mg/d PURINE 600 mg/d + H + Uric acid GI tract 200 mg/d • Mostly degraded by colonic bacteria Urine 600 mg/d Uric acid 1200 mg/d Uric acid (pool) 1200 mg/d • Glomerular filtration • Proximal reabsorption and secretion Urate transporters: URAT1 (gene SLC22A12) GLUT9 (gene SCL2A9) URAT1 = urate/organic anion exchanger 1 GLUT9 = glucose transporter 9
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Outline: Uric acid pathway Pharmacotherapy in Gout and ...Uric acid pathway Gout vs. hyperuricemia How to manage acute gout attack? Gout Chronic management of gout Hyperuricemia -Who
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Pharmacotherapy in Gout and Osteoarthritis
Thitima Doungngern, PharmD, MPharm, BCPSFaculty of Pharmaceutical Sciences
Prince of Songkla University
การประชมุวชิาการ วทิยาลยัเภสชับําบัดแหง่ประเทศไทยเรื=อง Contemporary Review in Pharmacotherapy 2013
SH: Drinks 2-3 cans of beer 5-7 night/weekEnjoy eating red meat, low-fat dairy products
almost daily
Which one of the following is the best way to diagnose the patient’s gout ?
A. Check joint for presence of monosodium urate
(MSU) crystals
B. Obtain synovial fluid gram stain and culture
C. Check serum uric acid concentration
D. Assess clinical symptoms
Criteria for diagnosis of gout
� Rome criteria (1963)
� New York criteria (1966)
American College of Rheumatology � American College of Rheumatology
preliminary criteria for gout (1977)
ACR preliminary criteria of diagnosis of acute gout
Meet at one of the following: � MSU crystals in synovial fluid during attack � Presence of proven tophous� At least 6 of the following criteria:
� More than 1 acute arthritis attack� Maximal inflammation developed within 1 day� Monoarthritis attack� Redness observed over joints� Redness observed over joints� First MTP joint attack � Unilateral first metatarsophalangeal joint attack � Unilateral tarsal joint attack� Suspected tophous� Asymmetric swelling within a joint on a radiograph � Subcortical cysts without erosions on a radiograph� Hyperuricemia � Synovial fluid culture negative for organisms during attack
Target of serum uric acid after treatment < 6 mg/dL< 5 mg/dL may be needed to improve S/Sx
Arthritis Care & Research 2012: 64:1431–1446.
Case 2
A 48 y/o male was prescribed allopurinol 100 mg QD and colchicine 0.6 mg BID a few days ago because of 3 episodes of acute gout attack in the past year.
He presents to your pharmacy with redness, swelling, and He presents to your pharmacy with redness, swelling, and intense pain in his right foot about 12 hours. He tells you that he never taken colchicine. He states “I didn’t understand why I needed two medications, so I only took allopurinol. Now I wonder if I should even take allopurinol because it isn’t working.”
Which one of the following is the most appropriate intervention for this patient ?
A. Discontinue allopurinol and start and NSAIDs
B. Discontinue allopurinol and start and colchicine
C. Continue allopurinol and start and NSAIDs
D. Continue allopurinol and start and a corticosteroid
LongLong--Term Management of GoutTerm Management of Gout
� Initiate ULT 1 – 2 weeks after the inflammation of the acute attack has resolved
� ULT may precipitate gout attack
� Use prophylaxis against acute attacks when initiating ULT:ULT:
� Colchicine 0.6 – 1.2 mg/d for up to 6 months OR
� NSAIDs/COX-2 inhibitors (for not more than 6 weeks)
� Consider losartan and fenofibrate for HTN and hyperlipidemia respectively, for their modest uricouriceffects
� Dose: 40 – 80 mg/day� Gout flare prophylaxis is recommended when
initialing therapy� Can use in patient with HLA-B*5801 polymorphism� Thromboembolic events (MI, stroke) have been � Thromboembolic events (MI, stroke) have been
� Absent of gout attack for > 6 months � may gradually decrease dose to maintain normal uric acid level (< 6 mg/dL)decrease dose to maintain normal uric acid level (< 6 mg/dL)
� ? Subtherapeutic dose -- may inhibit renal urate secretion
� Dose � Initial: 100–200 mg BID for 1–3 wks � 200–400 mg BID � Absent of gout attack for > 6 months � may gradually
decrease dose to maintain normal uric acid level (< 6 mg/dL)
� CrCl < 10 mL/min � loss of uricouric effect
� Platelet aggregation inhibitor (unclear MOA)
� CI: phenylbutazone allergy
peptic ulcer disease (may aggravate)
serious blood disorders
Uricosuric agents – Class Effects (probenecid, benzbromarone, sulfinpyrazone)
� Urolithiasis (urate stone) ∼ 10%
Prevention:
� Adequate fluid intake (10 – 12 glasses /day)
Maintain high urine pH � Maintain high urine pH
↑↑↑↑ urine pH … a diet high in citrus fruits, vegetables, or dairy products
↓↓↓↓ urine pH … a diet high in meat products or cranberries
� + Aspirin …. ↓ uricosuric effect
…. ↑ risk of bleeding (↓ aspirin excretion)
Pegloticase, IV � Pegylated recombinant form of urate-oxidase
enzyme (uricase)urate-oxidase
uric acid allantoin (water soluble metabolite)
� Approved for refractory gout � Approved for refractory gout � NOT for asymptomatic hyperuricemia � Prophylaxis gout flare (NSAID or colchicine) 1 week before
pegloticase and may continue for up to 6 months
� CI: G6PD deficiency � ? Risk of anaphylaxis and infusion-related reactions
� Premedicated with antihistamine + corticosteroid� Slow infusion in > 2 hours
Drug-induced Decreased Renal Urate Clearance
� Diuretics (Thiazides and Loops)
� Cyclosporin, Tacrolimus
� Low dose aspirin (< 325 mg/day)
� Ethambutol
Pyrazinamide� Pyrazinamide
� Ethanol (esp. beer and spirit, but not wine)
� Levodopa
� Methoxyflurane
� Laxative abuse (alkalosis)
� Salt restrictionhttp://health-fts.blogspot.com
DietDiet & Lifestyle for Gout Patients& Lifestyle for Gout Patients
� Acute onset of severe joint pain. � Swelling, effusion, warmth, erythema, and/or
tenderness of the involved joint(s).� Arthrocentesis with synovial fluid analysis shows
strongly MSU crystal.
� Acute onset of severe joint pain. � Swelling, effusion, warmth, erythema, and/or
tenderness of the involved joint(s).� Arthrocentesis with synovial fluid analysis shows
strongly MSU crystal.� NSAIDs, colchicine, or corticosteroids are used to treat
acute disease. � Allopurinol, uricosuric agents are used as uric acid-
lowering drugs when long-term prevention of crystal deposition is indicated.
� Complications include joint destruction, kidney disease, and urolithiasis.
� NSAIDs, colchicine, or corticosteroids are used to treat acute disease.
� Allopurinol, uricosuric agents are used as uric acid-lowering drugs when long-term prevention of crystal deposition is indicated.
� Complications include joint destruction, kidney disease, and urolithiasis.
Outlines:
� Overview
� Update ACR 2012
guideline
Osteoarthritis
� Glucosamine +
chondroitin in OA
� IA Hyaluronic acid in OA
Osteoarthritis (OA) is a disorder of diarthrodial joints that is characterized clinically by pain and functional limitations, radiographically by osteophytes and joint space narrowing, and histopathologically by alterations in cartilage and subchondral bone integrity.
OAOA
� Most prevalent form of arthritis
� Highly associated with aging (usually after age 40 - 50)
� Women > Men
� Commonly affected large weight bearing joints
� Exact cause of OA
– remains unclear
Pathophysiology of OA
MMP = metalloproteinasehttp://www.mdconsult.com
Clinical Manifestations� Pain
� [Early stage] exacerbated by activity and relieved by rest
� [Advanced disease] progressively less activity �
occurring at rest and at night
� Joint stiffness � Joint stiffness
� morning – usually resolved within 30 min
� after periods of inactivity Typical hand deformities in OA. Heberden's nodes are seen on the distal interphalangeal joints, and Bouchard's nodes are at the proximal interphalangeal joints.
Case 3W.F. is an 85-year-old man who presents to his physician with pain from hip OA. He also has HTN, CAD, and BPH. For his OA, W.F. has been taking acetaminophen 650 mg 3 times/day. W.F. reports that paracetamol helps, but he still experiences pain that limits his ability to walk.
Which one of the following is the best next step in analgesic therapy for W.F.?
A. Change the analgesic to ibuprofenB. Change the analgesic to celecoxibC. Add paracetamol + codeineD. Add glucosamine