PHRM 825: Gout - Wahl Flashcards
What is gout caused by?
A deposition of monosodium urate crystals in the synovial fluid or tissues
What disease is gout secondary to?
Hyperuricemia
What serum urate level diagnoses hyperuricemia?
> or = 6.8 mg/dL
What are the two clinical phases of gout?
- Intermittent acute attacks
- Chronic tophaceous gout
What 5 disease states increase your risk for gout?
- HNT
- T2DM
- Obesity
- Metabolic syndrome
- CKD
What dietary factors increase your risk for gout?
- Alcohol
- High in purines (meat and seafood)
- High fructose beverages
What 5 medications increase your risk for gout?
- Thiazide diuretics
- Loop diuretics
- Niacin
- Calcineurin inhibitors
- Aspirin (<1 g/day)
What 3 medication classes are used during an acute gout attack?
- NSAIDs
- Colchicine
- Corticosteroids
What NSAIDs are FDA approved for gout attacks?
- Naproxen
- Sulindac
- Indomethacin
- Celecoxib (COX-2 only)
What is the dosing for Naproxen for an acute gout attack?
250mg PO tid
What is the dosing for Sulindac for an acute gout attack?
750mg initially, then 250mg q8h
What is the dosing for Indomethacin for an acute gout attack?
200mg PO bid
What is the MOA of colchicine?
Disruption of microtubule formation – Prevents activation, migration, and degranulation of neutrophils which propagate immune response in affected joint
What is the dosing for Colchicine for an acute gout attack?
- 2 mg load once, then 0.6 mg an hour later
* resume/start maintenance 12 hours later
If on HD, 0.6mg once, do not re-dose for 2 weeks
What 5 meds interact with colchicine?
- Protease inhibitors
- Azole antifungals
- Clarithromycin
- Verapamil
- Statins
When are corticosteroids used for acute gout attacks?
- NSAID/colchicine intolerance
- Polyarticular involvement
- Resistant cases
What is the dosing for prednisone for an acute gout attack?
- 0.5 mg/kg/day for 5-10 days
- 0.5 mg/kg/day for 2-5 days then taper for 7-10 days
What is the dosing for methylprednisolone for an acute gout attack?
21 day dose pack
What is the dosing for Triamcinolone for an acute gout attack?
- 60 mg IM once, then oral prednisone
- 2.5-40 mg intra-articular injection once
5 adverse effects of corticosteroids
- GI toxicity (bleed/PUD)
- N/V/D
- Hyperglycemia
- Weight gain and increased appetite
- Fluid retention
Adverse effects of colchicine
- GI (N/V/D)
- Bone marrow suppression
- Neuromuscular
Adverse effects of NSAIDs
- GI (bleed/gastritis)
- Renal (AKI)
- Cardiovascular (Sodium/fluid retention, edema)
Which 2 treatment options for acute gout attack should not be given together?
NSAIDs and Oral corticosteroids (GI toxicity)
When is acute gout attack prophylaxis indicated?
When urate lowering therapy is being initiated
What are the goals of therapy for acute gout attacks?
- Relieve attack (preferable withing 24 hours)
- Continue urate lowering therapy (ULT)
- Patient education
What are the goals of therapy for chronic gout management?
- Prevent future attacks
- Reduce serum uric acid levels to < or = 6 mg/dL (or 5 in severe cases)
What constitutes a severe case of chronic gout management?
- Polyarticular involvement (4 or more joints)
- Tophi
What are 4 indications for ULT?
- Frequent acute attacks (2 or more/year)
- Tophi on exam or imaging
- Uric acid > 10mg/dL
- CKD stage 2 or worse
ULT monitoring
- every 2-5 weeks during initiation
- Every 6 months once goal <6 mg/dL achieved
What are 3 first-line ULT?
- Xanthine oxidase inhibitors
- Allopurinol
- Febuxostat
What are 2 second-line ULT?
- Uricosurics
- Probenecid
What are 2 third-line ULT?
- Uricase agents
- Pegloticase
What is the typical first choice xanthine oxidase inhibitor?
Allopurinol
Common Allopurinol adverse effects
- GI upset
- Skin rash
- Leukopenia
- Thrombocytopenia
- Increased LFTs
- HA
Allopurinol drug interactions
- Warfarin
- Mercaptopurine and azathioprine
- Pegloticase
What xanthine oxidase inhibitor is chosen when the patient has an allopurinol intolerance?
Febuxostat
Common Febuxostat adverse effects
- Rash
- Nausea
- Abnormal LFTs
MOA of probenecid
Inhibits reabsorption of uric acid in convoluted tubule of kidney
When is Probenecid used for chronic management of gout?
- Documented underexcretion of urate
- Patient resistant/intolerant to allopurinol
- Cannot reach target urate on monotherapy with XOI
- May also be added to allopurinol
Probenecid adverse effects
- Rash, flushing, HA
- GI upset
- Stone formation (increase fluid intake)
Probenecid contraindications
- History of uric acid kidney stones
- Concomitant salicylates, especially >325mg/day
- Overproducers of uric acid
- CrCl <50mL/min
MOA of Uricase agents
Metabolizes uric acid to allantoin (excreted 10x more effectively in the urine)
When are uricase agents used for chronic management of gout?
- Last-line agent
- Indicated for refractory chronic gout (patients with significant disease burden and refractoriness to (or intolerance of) conventional urate lowering therapy)
Adverse effects of Pegloticase
- Infusion reactions
- Anaphylaxis
- Nephrolithiasis
- Arthralgias
- HF exacerbation
- Nausea
Contraindications/cautions for Pegloticase
- G6PD deficiency
- HF
MOA of Lesinurad
URAT1 inhibitor (enhances uric acid excretion)
When is Lesinurad used?
In combo with XOI
Adverse effects of Lesinurad
- Black box warning: acute renal failure (monotherapy)
- HA
- GERD
Fenofibrate MOA
Increases clearance of both hypoxanthine and xanthine (decreases urate levels 20-30%)
Losartan MOA
Inhibits tubular reabsorption of uric acid increasing urinary excretion
