Gout Flashcards
Should we treat patients with asymptomatic hyperuricemia?
-Uh uh uh uh uh No
When you find gout, what should you screen for?
- HTN, DM, CKD, & hyperlipidemia
- Gout = metabolic syndrome
What are the goals of gout therapy??
- Treat acute disease: NSAIDs, colchicine, steroids
- Preventing flares/recurrences: Prophylaxis of Colchicine or NSAIDs during initiation of urate-lowering agent (allopurinol, probenecid)
What NSAIDs are recommended for acute gout?
- Use ibuprofen or naproxen
- Take until acute gouty attack is completely resolved
Oral prednisone is indicated for patients with what comorbidities due to its safety profile?
-Oral prednisone for patients with kidney disease, cirrhosis, and heart failure
What drug is “last resort” for acute gout management given cost and drug interactions
-Colchicine
What three drugs are all 1st line for acute gout management? How do we choose between them?
- Colchicine, steroids, NSAIDs
- Choice should be based on patient preference, prior response, & other comorbidities
- Avoid systemic corticosteroids + NSAIDs due to synergistic GI toxicity
Colchicine Indications
- used for ACUTE gout flares*
- Added to ASA in the context of pericarditis
- Familial Mediterranean Fever
It is pricey $$$
Colchicine CYP interactions
- Major substrate of 3A4 & PgP
- Fatal toxicity reported in patients with a strong inhibitor of CYP3A4 (clarithromycin) or P-gp (cyclosporine)
When you mix colchicine with a statin or a fibrate, what is possible?
-Myopathy and rhabdomyolysis
What is the ADR associated with almost everyone in the old dosing regimen?
-Poopy pants diarrhea
What is involved in the comprehensive gout assessment with the goal of prevention of acute attacks?
- BP, BMI assessment
- ETOH use
- Smoking
- CV risk
- BUN/Cr, eGFR
- Glucose
- Lipids
What are some non-pharm recommendations/dietary changes for gout patients?
- Weight loss
- Exercise
- Avoid sugar sweetened beverages & foods with added sugars
- Avoid High purine meats
- Avoid alcohol (beer»spirits)
What were the three bolded populations that get anti-hyperuricemic therapy?
- Frequent/disabling gouty attacks
- Gout with CKD
- Men <25 years old or premenopausal women
You initiate anti-inflammatory prophylaxis when starting or just prior to starting UA lowering meds. What meds do we use? How long do we take them?
- 1st line: colchicine, NSAIDs
- 2nd line: Low dose prednisone
-minimum of 6 month duration
Xanthine Oxidase Inhibitors
- Allopurinol > febuxostat
- first line options
Uricosuric Agents
- Probenecid: essentially a uric acid diuretic
- Fenofibrate and losartan also used and can be added to a xanthine oxidase inhibitor
-What is the “treat to target” theory in gout. What is a pearl about how fast we lower uric acid
- Goal is to get serum urate <6 or <5 if tophi are present
- Lowering slowly associated with lowest rate of recurrent acute attacks
When do you usually start anti-hyperuricemic therapy? (think about timing with the flares)
- Generally start 2-4 wks after flare resolution
- Duration of therapy indefinite to remain effective
Allopurinol MOA
-Inhibition of conversion of hypoxanthine to xanthine to uric acid
Allopurinol indications
- Prevention of hyperuricemia associated with gout & urate nephrolithiasis
- Also used to prevent acute uric acid nephropathy during chemotherapy for malignancies (tumor lysis syndrome*)
Prior to initiation of allopurinol, what gene do we need to screen for and why?
- HLA-B*5801 (Just know HLA testing)
- at higher risk for hypersensitivity rxns
Should we stop xanthine oxidase inhibitors during acute attacks?
-Uh uh uh uh uh No
What is a pearl about the dosing of Allopurinol?
- Adjust for GFR due to accumulation of alopurinol and metabolites
- Low and slow! Doses gradually increased 2-4wks based on serum UA
Allopurinol Monitoring
- CBC
- LFTs periodically
- Serum Uric acid
You should avoid allopurinol in patients taking these three drugs
- 6-metacaptopurine
- Azathioprine
- Theophylline
Allopurinol ADRs
- Paradoxical gout flare: encourages crystal shedding through partial crystal dissolution**
- Bone marrow suppression
- Drug rash/fever
Allopurinol “Special ADR’s”
-DRESS syndrome: fever, rash, hepatitis, eosinophilia, AKI
Febuxostat MOA
- Xanthine oxidase inhibitor
- Not a purine base analogue (unlike allopurinol)
Febuxostat indications
- Same as allopurinol
- Use in patients intolerant to allopurinol
Febuxostat ADRs
- Paradoxical gout flare
- LFT abnormalities
Probenecid MOA
-Promotes UA clearance by inhibiting the urate-anion exchanger at the proximal tubule which modulates reabsorption of urate
“urate diuretic”
Probenecid Indications
- Prevention of hyperuricemia secondary to impaired renal excretion of UA ass with gout
- Pts must have adequate renal fcn (CrCl >50 mL/min)
Probenecid Contraindications
-Don’t use in patients with prior nephrolithiasis
Probenecid ADRs
- May precipitate acute gout*
- Uric acid stone formulation*
- Rash
- N/V/D
Pegloticase MOA
- Reduces serum UA by catalyzing oxidation of UA, which makes it easier to excrete (allantoin)
- Used to treat chronic severe symptomatic gout in adults who have not responded to maximum doses of xanthine oxidase inhibitor
Pegloticase CI/ADR
-CI in G6PD deficiency
ADR
- Paradoxical gout flare, maybe severe
- Infusion rxns
- Anaphylaxis
What two drugs are used for off-label gout tx?
- Losartan
- Fenofibrate
