Gout and Hyperuricemia Flashcards
NSAIDs MOA
Provide relief by inhibiting cyclooxygenase 2 (COX-2) mediated prostaglandin synthesis at the site of injury
NSAIDs Drugs
Indomethacin
Naproxen
Sulindac
Corticosteroids MOA
Decreases inflammatory response
- inhibits synthesis and release of cytokines with reduced activation of T cells and fibroblast proliferation
- inhibits pro-inflammatory transcription factors
Corticosteroids Therapeutic Use
- For those who can’t tolerate NSAIDs
- For when the infection has been ruled out
- associated with rebound flares of acute gout
- may be given systematically for polyarticular attacks
- may be given intra articularly for monoarticular attacks
NSAIDs Therapeutic Use
- Provide pain relief within 2-4 hours
- Treatment required for 7-14 days
NSAID administration
- Treatment within 24 hours of symptoms: potent NSAID
- Days into attack: NSAID with lower side effects
- With improvements, cut dose in half
- treatment required for 7-14 days
Colchicine MOA
- Selective inhibitor of microtubule assembly; reduces leukocyte migration and phagocytosis, thus decreasing inflammation
- Reduces inflammatory response to deposited crystals
Colchicine Use
- Not an analgesic
- Does not affect renal excretion of uric acid
- Does not alter plasma solubility of uric acid
- Neither raises nor lowers serum uric acid
Colchicine ADRs
- GI: Diarrhea, nausea, vomiting, abdominal pain
- Heme: anemia, leukopenia, neutropenia, thrombocytopenia, and aplastic anemia
- Hepatic: hepatomegaly, elevated liver enzymes
- Myopathy
Colchicine DDI
Statins
Fibrates (gemfibrozil)
Digoxin
Prophylatic Therapy
Should be initiated before the initiation of a hypouricemic agent and continued during the use of a hypouricemic agent (administer a small dose of colchicine or NSAID)
What Patients should use Prophylatic Therapy?
- severe attacks of gouty arthritis
- a complicated course of uric acid nephrolithiasis
- a substantially elevated serum uric acid level (>10 mg/dl)
- 24 hr urinary excretion of uric acid or more than 1000 mg
Uricosuric Therapy MOA
Antagonist at URAT 1 Transporter to block uric acid reabsorption: increases Uric Acid Excretion
Patients that use Uricosuric Agents
- normal renal function (CrCl>50 mL/min)
- underexcrete uric acid
- negative history of nephrolithaisis
- NOT effective in overproducers
Uricosuric Agent complications
may precipitate nephrolithiasis
Xanthine Oxidase Inhibitor: Febuxostat
- Chronic management of Hyperuricemia
- No dose adjustment for patients with mild to moderate renal impairment
Xanthine Oxidase Inhibitor: Febuxostat contraindications
Contraindicated with patients on azathioprine, mercaptopurine, or theophylline
-monitor liver function for elevations in transaminase
Black Box warning for Febuxostat
- Increased risk of death
- higher rate of heart related death and death from all causes
- reserved for patients who failed or do not tolerate allopurinol
Xanthine Oxidase inhibitor: Allopurinol MOA
Inhibits xanthine oxidase (stops hypoxanthine to xanthine to uric acid conversion) . which STOPs uric acid production
Allopurinol DDIs
- Azanthioprine
- Mercaptopurine
- ACEI (steven johnson’s rash)
- Warfarin
Allopurinol ADE
Hypersensitivity Reactions: fever, leukocytes, eosinophilia, skin rash, elevated SCr
Predisposing factors: renal dysfunction, thiazide diuretic, dose
Allopurinol and high risk patients’ hypersensitivity
HLA-B*5801 screening for high risk population
- At risk: Korean descent with stage 3 or worse CKD
- Han Chinese or Thai descent
Rasburicase MOA
Catalyzes oxidation of uric acid to readily eliminate metabolite (allatoin)
Rasburicase is FDA approved for:
Hyperuricemia, due to malignancy, in patients with or patients with or at risk for tumor lysis syndrome
Rasburicase Black Box Warning
Anaphylaxsis
Hemolysis
Methemoglobinemia
Probenecid MOA
-Increases uric acid secretion by blocking URAT 1 transporter
Probenecid Dosing and Side effects
- Dose: start low
- side effects: GI, hypersensitivity, watch for low dose aspirin
Pegloticase MOA
- Catalyzes oxidation of uric acid fast to readily eliminate metabolite allatoin
- FDA approved
- 8 mg administered IV once every 2 weeks
Pegloticase Black box warning
- Anaphylaxsis (6.5%)
- Infusion Reactions (26%)
- G6PD deficiency associated hemolysis and methemglobinemia
Pegloticase administration
patients should be premedicated with anti histamtines and corticosteroids and treated in a health care setting
Lesinurad MOA
Uric Acid Transporter inhibitor: stops uric acid reabsorption
Lesinurad in treatment
used in combination with Xanthine Oxidase inhibitor for treatment of hyperuricemia
-do NOT start if creatinine clearance is below 45 mL/min
When to use Antihyperuricemic therapy
- Patient has frequent acute attacks (more than 1-2/year)
- Clinical or Radiographic signs of chronic gouty joint disease
- Presence of Tophaceous Gout
- Evidence of urate nephrolithiasis
Potential complication with Anti hyperuricemic agents
It may cause an attack or worsen it, so give a low dose NSAID or colchicine initially
