Gout Patho Lecture 2024 PDF

PHM 101: General Medicine Gout March 8, 2024 Amita Woods, Pharm D Clinical Pharmacy Manager University Health Network The Gout (James Gillray, 1799)  Video https://www.youtube.com/watch?v=4edrfpzg 9wQ  Objectives To u...

PHM 101: General Medicine Gout March 8, 2024 Amita Woods, Pharm D Clinical Pharmacy Manager University Health Network The Gout (James Gillray, 1799)  Video https://www.youtube.com/watch?v=4edrfpzg 9wQ  Objectives To understand the pathophysiology of Gout for the purpose of – Patient education – Identifying drug therapy problems Assessing therapeutic alternatives in different patients – Developing a Care Plan Goals/endpoints of therapy – Providing Recommendations to other HC practitioners Detailed discussion of drug therapy will be covered in the workshops  Gout What is it? – A condition in which monosodium urate (uric acid) crystals deposit in joints and soft tissues (cartilage, bursa, tendon, etc) causing pain, inflammation and disability 4 stages of Gouty Arthritis 1. asymptomatic hyperuricemia, 2. gouty flare, 3. intercritical gout prophylaxis of gouty flare and management of hyperuricemia 4. chronic gouty arthritis  Which of the following individuals is most at risk of developing gout? a) Young healthy male b) Frail, elderly, underweight female c) 50 year old male who is overweight, hypertensive and drinks alcohol d) PMH 101 student because they spend so much time sitting, studying, and drinking lots of coffee  Epidemiology “Disease of Kings” Incidence and prevalence increasing in Western industrialized countries No longer restricted to populations with high standard of living Why? Increased longevity Dietary habits Sedentary lifestyle Increased obesity Increased metabolic syndrome  True or False Gout is more common in males than females Obesity is a risk factor for gout Gout is more common in a younger age Use of Diuretics is a risk factor  Risk Factors Direct linear correlation between serum uric acid concentration and gout - If uric acid level is drawn in symptomatic individuals, it usually will be elevated Elevated serum uric acid levels Increased age Male gender (3X higher, but less so after menopause) Increased body weight, sedentary lifestyle Metabolic syndrome Dietary: Alcohol intake, sugary beverages, red meat Increased serum creatinine and BUN Use of thiazide and loop diuretics Genetics?  Precipitating Factors Stress Medications Diuretics Trauma Levodopa Infection Cyclosporine Surgery Niacin Salicylates Alcohol Cytotoxic Drugs  Pathophysiology Production of uric acid is terminal step in degradation of purines Uric acid serves no physiologic purpose (waste product) Under normal conditions amount of uric acid accumulated is 1200mg in men and 600mg in women – Near upper limit of urate solubility Urate pool increases in gout: Overproduction Underexcretion  Overproduction of Uric Acid 3 Sources of Purines 1. Diet 2. Conversion of tissue nucleic acid to purine nucleotides 3. De novo synthesis of purine bases Purines enter a common metabolic pathway leading to production of either nucleic acid or uric acid Uric acid accumulates if production exceeds excretion (avg prod 600-800mg UA/day) Enzyme systems regulate purine metabolism which can result in overproduction of uric acid  Overproduction of Uric Acid Uric acid may also be over-produced due to increased breakdown of tissue nucleic acids and excessive rates of cell turnover – Myeloproliferative & lymphoproliferative disorders – Psoriasis – Polycythemia vera – Certain anemias Especially important to assess in patients who present with gout before age of 25 or those with renal stones  Underexcretion of Uric Acid Under normal conditions: – 2/3 uric acid excreted in urine – 1/3 eliminated via GI tract after enzymatic degradation by colonic bacteria Primary idiopathic hyperuricemia – Majority of patients with gout have a relative decrease in renal excretion of uric acid for an unknown reason  Hyperuricemia Males: serum levels >416 umol/L Females: serum levels >357 umol/L Overproducers: Individuals with hyperuricemia who excrete >1000mg of UA/ 24hrs  Signs and Symptoms of Gout Generally presents as acute inflammatory monoarthritis Onset: Usually at night Duration: 3-14 days (untreated) Lower extremity involvement – 85% of initial attacks involve a single joint – Any joint can be involved (insteps, ankles, knees, wrists, fingers and elbows) –Most often: first metatarsophalangeal joint (great toe) = “Podagra” (50%) Podagra  Diagnosis Definitive - visualization of uric acid crystals in joint fluid by aspiration Presumptive diagnosis 1. Inflammatory monoarthritis 2. Elevated UA 3. Response to colchicine Lab test: high UA level, leukocytosis Long standing gout: xray – asymmetric swelling Xray https://www.hss.edu/conditions_gout-risk-factors-diagnosis-treatment.asp  Acute Classic Attack Rapid, localized onset of excruciating pain (night), swelling, redness and inflammation Typically monoarticular at first, affecting big toe and may include other joints Debilitating Unilateral attack – lasting 3-14 days, maximal severity within 12-24 hrs Complete resolution (untreated): Days to Weeks Crystal-induced inflammation: number of chemical mediators cause vasodilation, increase vascular permeability, increase in polymorphonuclear leukocytes – Lysis of PMNs  inflammation  Why are we concerned - incidence and prevalence of gout is increasing, reflecting the fact that at-risk populations are increasing. - association between gout and metabolic syndrome has been established, as well as an increased risk of cardiovascular mortality in middle-aged men diagnosed with gout - Studies have also shown that greater reduction of serum uric acid levels is associated with greater preservation of renal function  Intercritical Gout Most untreated patients experience a second episode within 2 years – 62 % within 1 year – 78 % within 2 years – 93% within 10 years Typically uric acid lowering treatments begin if >2 flares per year Gutman AB, Gout and gouty arthritis in Textbook of Medicine. Saunders  Intercritical Gout If left untreated, trend toward recurrent acute attacks – Occur in progressively shorter asymptomatic periods – Increasingly prolonged and disabling, polyarticular, occasionally associated with a fever  Tophaceous Gout/ Chronic Gouty Arthropathy Bony erosions/deformities may develop – Typically associated with chronic tophaceous (crystal) deposits (collections of solid uric acid in connective tissue) Most common sites: base of fingers, olecranon bursae, ulnar aspect of forearm, achilles tendon, knees, wrists and hands Tophaceous Gout Deposits of urate in soft tissues  Treatment Goals Terminate AcuteAttack – Goal is to control inflammation and pain Prevention of acute and chronic gout – Goal is to lower uric acid level to prevent precipitation, acute attacks, and formation of tophi  Nonpharmacologic Therapies Be aware of what they are – How you would educate a patient – Tailor therapy to specific patient What their role is in the management of a patient with gout – Acute attack – Prevention/ Chronic management  Pharmacologic Treatment Options of Acute and Chronic Acute Chronic NSAIDs Xanthine Oxidase Inhibitors Oral colchicine Allopurinol Corticosteroids Febuxostat Oral Uricosurics Intramuscular Probenecid Intra-articular (not available in canada)  Workshop Be sure to read case carefully Use your thought process to help resolve any actual and potential DTPs Identify risk factors for patient, frequency of attacks Define your goals ie treat an acute attack and/or if your patient meets criteria for prophylaxis Determine best treatment for the patient and how to monitor if it is working or not  Cases for Workshop posted WORKSHOP WED - Read Gout Chapter from Rheumatologic Disorders Section in Dipiro Text (Pages 1490-1501) - Read Gout chapter from Patient Self Care - Read 2020 ACR(American College of Rheumatology) Guidelines (pages 747- 755 – focus on pharmacological management and monitoring) “What if” scenarios - be prepared to discuss in workshop