Gout Exam Preparatory Course PDF

Za hr a vi (ID :1 Evaluating Exam Preparatory Course 01 41 0) GOUT Le yla 1 LEGEND Li ce ns ed to AHS: Allopurinol Hypersensitivity Syndrome CVD: Cardiovascular Disease UA: Uric Acid Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 2 Copyright © 2023 PharmAchi...

Za hr a vi (ID :1 Evaluating Exam Preparatory Course 01 41 0) GOUT Le yla 1 LEGEND Li ce ns ed to AHS: Allopurinol Hypersensitivity Syndrome CVD: Cardiovascular Disease UA: Uric Acid Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 2 Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 1 WHAT IS GOUT AND WHAT ARE THE SYMPTOMS? Inflammatory disease marked with uric acid or urate crystal deposits in joints, soft tissues (e.g. cartilage), and renal tissues (e.g., glomeruli), where the deposits are responsible for severe arthritis or joint pain • Tophi/tophaceous gout are chronic complications of gout: large, visible bumps/nodules in soft tissue consisting of uric acid crystals leading to pain and inflammation Gouty Arthritis Intercritical Gout :1 • after the first gout flare, when a person is asymptomatic, they are in this phase. • Primary goal here is prophylaxis of another gout flare (ID • quick onset of excruciating pain and inflammation in night or early morning. 85% of attacks start off as monoarticular (big toe most common). • This is also known as a gout attack/flare up. Chronic Gouty Arthritis • occurs usually 12 years from onset (only 2% of patients develop severe crippling disease). • Aims of therapy are to control pain and inflammation Za hr a • elevated serum urate levels (>360 umol/L in females, >420 umol/L in males) without any clinical manifestations Gouty Flare vi Asymptomatic Hyperuricemia 01 41 0) • Other than tophi, other complications of hyperuricemia include uric acid nephrolithiasis (kidney stones), and nephropathy Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. Le yla 3 WHAT IS GOUT AND WHAT ARE THE SYMPTOMS? Inflammatory disease marked with uric acid or urate crystal deposits in joints, soft tissues (e.g. cartilage), and renal tissues (e.g., glomeruli), where the deposits are responsible for severe arthritis or joint pain to • ed • Tophi/tophaceous gout are chronic complications of gout: large, visible bumps/nodules in soft tissue consisting of uric acid crystals leading to pain and inflammation Li ce ns • Other than tophi, other complications of hyperuricemia include uric acid nephrolithiasis (kidney stones), and nephropathy Gouty Arthritis • Asymptomatic hyperuricemia: elevated serum urate levels (>360 umol/L in females, >420 umol/L in males) without any clinical manifestations • Gouty flare: quick onset of excruciating pain and inflammation in night or early morning. 85% of attacks start off as monoarticular (big toe most common). This is also known as a gout attack/flare up. • Intercritical gout: after the first gout flare, when a person is asymptomatic, they are in this phase. Primary goal here is prophylaxis of another gout flare • Chronic gouty arthritis: occurs usually 12 years from onset (only 2% of patients develop severe crippling disease). Aims of therapy are to control pain and inflammation Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 4 Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 2 WHAT IS THE PATHOPHYSIOLOGY OF GOUT? Foods high in purines include red meats, beer, fish and shellfish 01 41 0) Overproduction of uric acid: higher purine intake, abnormal enzymes and regulation :1 Uric acid is the end waste product of purine metabolism and is renally excreted. Gout is a disorder where excess uric acid builds up to form and deposit urate crystals in joints, soft tissues (e.g. tendon or cartilage), or renal tissues (e.g. glomeruli) Under-secretion: Za hr a vi (ID reabsorption of uric acid in the kidney due to dehydration, etc. Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 5 Le yla WHAT ARE THE RISK FACTORS THAT INCREASE THE OCCURRENCE OF HYPERURICEMIA AND GOUT? Excess alcohol intake • Atherosclerosis • Chronic kidney, glomerular, and interstitial renal disease • Diabetes • Hyperlipidemia • Hypertension • Ischemic heart disease • Lead intoxication • Metabolic syndrome • Myeloproliferative disorders and some cancers • Obesity • History of urolithiasis • Genetic and/or acquired causes of uric acid production (rare) Li ce ns ed to • What are examples of medications that increase the risk of hyperuricemia and gout? Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 6 Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 3 Terminate the acute attack of arthritis • Prevent recurrence • Prevent or reverse complications • Treat associated disorders • Minimize side effects associated with drug therapy Za hr a vi (ID :1 • 01 41 0) WHAT ARE THE GOALS OF THERAPY? Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. Le yla 7 For atypical sign/symptoms, aspiration of synovial fluid is needed ed Li ce ns Classical symptoms of gout is usually enough for accurate diagnosis to HOW IS GOUT DIAGNOSED? Screening for other comorbidities Radiographs for diagnosing chronic gout Uric acid levels are important for monitoring BUT NOT DIAGNOSIS • People with high UA levels might have no symptoms – don’t treat • UA levels are normal during an acute attack Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 8 Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 4 HOW CAN GOUT ATTACKS BE PREVENTED IN THE FUTURE? • Avoid alcohol during acute attacks, and no more than 1-2 drinks a day during maintenance (maximum of 2 in men and 1 in women per day) • Avoid drinks high in fructose 01 41 0) • Avoid foods high in purines (e.g. sweetbreads, liver, kidney) • Limit consumption of meat (beef, lamb, pork, seafood), naturally sweet fruit juices, salt, table sugar, sweetened beverages • Encourage Regular exercising to avoid weight gain • Non-fat dairy products and vegetables, staying hydrated Za hr a vi (ID :1 • Smoking cessation Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. Le yla 9 HOW SHOULD ACUTE GOUT ATTACKS BE TREATED? NSAIDs (indomethacin, naproxen, ibuprofen most common) Treat gout attacks as soon as possible as the efficacy of drug therapy decreases over time ed Colchicine to • NSAIDs can be used up to 24 hours from the onset of an acute gout attack (taken up to 2-3 days after gout symptoms resolve) however if onset of attack is over 24 hours and/or NSAIDs are contraindicated or not tolerated, patients can use colchicine Li ce ns • Antimitotic mitigating the inflammatory response by neutrophils that contribute to gout symptoms; best used within 12 hours of onset (can be used within 36 hours of onset) • Side effects: primarily GI (nausea, vomiting, and diarrhea that resolve with dose reduction and drug discontinuation) whereas chronic side effects include alopecia, bone marrow suppression, neuropathy • Trial done in 2019 demonstrated that colchicine was effective in secondary prevention of major cardiac events after a myocardial infarction • Colchicine is a major substrate of CYP3A4 and P-glycoprotein Corticosteroids (Oral, Intra-articular, or intramuscular) • Equally or superior efficacy as NSAIDs and colchicine and have no greater risks of adverse effects in most patients • Prednisone or prednisolone 30-40mg is given over a period of 7 – 10 days • Intra-articular or intramuscular can be used for patients who cannot tolerate oral corticosteroids Note, both colchicine and NSAIDs are not recommended in severe renal impairment. If patients have severe renal impairment and/or onset of pain was over 36 hours, consider oral corticosteroids. Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 10 Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 5 WHAT ARE THE AVAILABLE URATE-LOWERING THERAPIES? Allopurinol (Xanthine Oxidase Inhibitor) :1 01 41 0) • 1st line and mainstay of treatment; started at a low dose and titrated slowly either to serum levels <360 µmol/L or to “target symptoms” • Titrating is key to prevent AHS (severe potentially life-threatening drug that can present as Steven-Johnson’s syndrome, toxic epidermal necrolysis, and systemic organ diseases) • Risk factors for AHS associated with allopurinol: initiating at high dose, renal impairment, positive for HLA-B*5801 allele (allele present mostly in Han Chinese, Thai, Korea, and African American patients, concomitant diuretic use (ID Febuxostat (Xanthine Oxidase Inhibitor) Za hr a vi • When allopurinol is ineffective, not tolerated, or due to patient specific factors (renal impairment does not require dosage adjustments whereas with allopurinol dosage adjustments are required in renal impairment) • Increases the risk of CVD-related deaths in gout patients with established CVD Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 11 Le yla HOW SHOULD GOUT ATTACKS BE PREVENTED USING URATELOWERING THERAPY (ULT)? Should all patients with gout start ULT? ed to The following patients are strongly recommended to start ULT prophylaxis Li ce ns • Patients with >2 gout flares per year • Patients with >1 subcutaneous tophi • Evidence of radiographic damage (seen with any imaging modality) The following patients are conditionally recommended to start ULT prophylaxis (decision to start is based on specific patient characteristics e.g., established CVD) • • • • ULT can be initiated DURING a gout attack! Why was it NOT recommended to start ULT during an acute attack in the past? Patients with infrequent flares (>1 flare but <2 per year) Patients with moderate-severe chronic kidney disease (stage 3 or more) Patients with serum uric acid levels >9 mg/dL Patients with urolithiasis Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 12 Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 6 WHAT IS INTERCRITICAL PROPHYLAXIS AND HOW DOES THIS AFFECT DRUG THERAPY? At least 6 months • 3 months after achieving target serum urate and no tophi on exam • 6 months after achieving target serum urate and 1 or more tophi on exam Za hr a vi (ID :1 • 01 41 0) • Even though ULT reduces serum uric acid levels after 1 year, within the first 6 months of ULT initiation, patients are most at risk for recurrent gout flares thus, it is advised that patients use colchicine 0.6 mg once or twice daily or low dose NSAIDs (e.g., naproxen 250 mg BID or indomethacin 25 mg BID) for the longer of the 3 options: Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. Le yla 13 REFERENCES 5. 6. 7. 8. 9. 10. 11. to 4. ed 3. Allopurinol, Celecoxib, Colchicine, Febuxostat, Ibuprofen, Indomethacin, Naproxen, Prednisone . In: Lexi-Drugs. Lexi-Comp, Inc. Burns CM, Wortmann RL. Latest evidence on gout management: what the clinician needs to know. Ther Adv Chronic Dis. 2012;3(6):271-286. doi:10.1177/2040622312462056 Clebak KT, Morrison A, and Croad JR. Gout: Rapid Evidence Review. Am Fam Physician. November 1 2020;102(9):533-538. https://www.aafp.org/afp/2020/1101/p533.html Fitzgerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180. Gaffo AL. Treatment of gout flares. In: Post T, ed. UpToDate. UpToDate. Gout and Hyperuricemia. In: Schwinghammer TL, DiPiro JT, Ellingrod VL, DiPiro CV. eds. Pharmacotherapy Handbook, 11e. McGraw-Hill. Kapur S. Gout and Hyperuricemia. In: Compendium for Therapeutic Choices. Canadian Pharmacists Association. Khanna D, Fitzgerald JD, Khanna PP et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012;64(10):1431-46. DOI: 10.1002/acr.21772. Khanna D, Khanna PP, Fitzgerald JD et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken) 2012;64(10):1447-61. DOI: 10.1002/acr.21773. Neogi T, Jansen TL, Dalbeth N, et al. 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatol. 2015;67(10):2557-2568. doi:10.1002/art.39254. Richette P, Doherty M, Pascual E et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017;76(1):29-42. doi:10.1136/annrheumdis-2016-209707. Li ce ns 1. 2. Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 14 Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 7 CHANGE LOG March 2020 • Slide 11: added information in the “Comments” section • Slide 15: Added information in the “Comments” section May 8, 2020 • Slide 9: made changes to the following statement: “Indication: >2 attacks/year, or kidney disease stage >2 or presence of tophus” 01 41 0) April 13, 2021 • Content reviewed; no changes made February 23, 2022 • Content reviewed; significant changes made February 25, 2022 • Slide 10: changed >2 to >2 gout flares • Slide 10: changed >1 to >1 subcutaneous tophi August 15, 2022 • Content reviewed; significant changes made on slide 3 (ID :1 March 5, 2023 • Made significant updates to slide 9 (added corticosteroid recommendation as first line) • No other changes made Za hr a vi August 14, 2023 • Content reviewed • Formatting changes made throughout Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. Li ce ns ed to Le yla 15 Copyright © 2023 PharmAchieve Corporation Ltd. Private and Confidential. 8