Gout and Hyperuricemia Flashcards
Medications that are risk factor for gout and hyperuricemia
Thiazide diuretics Low- to moderate-dose aspirin Ethambutol Nicotinic acid Vitamin B12 Cyclosporine Levodopa Pyrazinamide Cytotoxic agents Ethanol
Hyperuricemia
uric acid, serum greater than 6.8 mg/dL
NSAIDs for gout
- All NSAIDs are equally effective
- Treatment should continue until symptoms subside (1-2 weeks)
Colchicine STEPS - Safety
- Doses greater than 4mg may cause multiple organ failure and death
- Dose adjustment not necessary when CrCl > 30ml/min
- Do not use more than one acute treatment every 2 weeks
- Do not use more than 0.3mg daily for prophylaxis initially
- Metabolized by the cytochrome P450 3A4 enzyme (elevated plasma colchicine levels can lead to fatal toxicity)
- Risk of adverse hemaatologic events includes myelosuppression, leucopenia, thrombocytopenia, and/or pancytopenia
Colchicine STEPS - Tolerability
- GI discomfort
- Diarrhea
Colchicine STEPS - Efficacy
New dosing decreases the likelihood of adverse events without affecting efficacy
Colchincine STEPS - Preference (Pearls)
Slower to work than NSAIDs for pain relief, but still a 50% reduction in pain at 24 hours
Cholchicine STEPS - Simplicity
!.2mg within 12 hours of onset and 0.6mg 60 minutes later. 2012 ACR recommendations suggest 0.6mg every 12 hours until acute symptoms resolve, starting immediately after the second 0.6-mg treatment dose.
Corticosteroids in Gout
- Excellent option for patients with acute gout and renal insufficiency
- Prednisone is equal in efficacy to NSAIDs for reducing pain and discomfort
- Intra-articular corticosteroids are especially effective with large joint involvement
- Intra-articular formulations show benefits 48 hours after injection
Nonpharmacologic prevention of recurrent gout attacs
1) adequate hydration (2 L or more of water per day
2) Discontinue diuretic therapy
3) Moderate, low impact exercise
4) Restrict dietary animal and yeast purine intake and alcohol (especially beer)
5) Avoid highly refined carbohydrates
6) Weight reduction
Consideration and expectation of prevention of gout attacks
1) Consider preventative therapy in individuals experiencing more than one acute gouty attack, per year
2) Therapy goal is serum uric acid concentrations less than 5-6 mg/dL
3) 2012 guidelines suggest that prophylactic therapy can be started during an acute gout attack, provided anti-inflammatory management has been started
4) Evaluate serum uric acid levels every 3 months for the first year after an attack and then annually thereafter
5) May attempt to discontinue agents at any time, but most will have at least one gout attack (90%) during the next 10 years
Xanthine oxidase inhibitors
Allopurinol (Zyloprim)
Febuxostat (Uloric)
Allopurinol STEPS - safety
- Exfoliative dermatitis
- Stevens-Johnson Syndrome
- Hepatotoxicity
- Mucositis
- Renal Insufficiency
- Thiazides decrease excretion of allopurinol
Allopurinol STEPS - Tolerability
- Elevated transaminases or alkaline phosphatase
- Useful to reduce tophi in patients with tophaceious gout
Allopurinol STEPS - Preference (Pearls)
- 1st line agent for prevention of recurrent gout and hyperuricemia
- Evaluate renal function for possible dose adjustments
- NOT for patients with asymptomatic hyperuricemia
- Do not stop therapy during an attack if the patient is already managed on allopurinal
- Start at 100mg daily and titrate by 100 mg a day every 2-4 weeks (max dose 800mg/day) to achieve a uric acid concentration less than 5-6mg/dL
- Maximal dose should be 200mg/day wiht CrCl less than 20ml/min and less than 100mg/day with CrCl less than 10ml/min
- 2012 ACR guidelines suggest HALB*5801 testing for at-risk populations (Korean patients with CKD stage 3 or works, Han Chinese or Thai descent
Allopurinol STEPS - Simplicity
- Daily dosing
- Relatively inexpensive (less than $20 a month)
Febuxostat STEPS - Safety
- Contraindicated in patients using azithromycin, mercatpopurine, or theophylline (Canada only)
- Higher incidence of cv events observed compared with incidence in patients using allopurinol, though no causal relationship has been proved
- Hepatotoxicity
Febuxostat STEPS - Tolerability
Arthralgias
Nausea
Rash
Febuxostat STEPS - Efficacy
Approved for treatment of hyperuricemia in patients with gout
Febuxostat STEPS - Simplicity
- Daily dosing
- Considerably more expansive than allopurinol (about $150-$200 per month)
Uricosuric Agent
Probenecid
Probenecid STEPS - Safety
- Avoid use in patients with uric acid kidney stones
- May worsen existing blood dyscrasias
- Many drug interactions and may increase the serum concentration of target agents
Probenecid STEPS - Tolerability
Dyspepsia
Reflux esophagitis
Probenecid STEPS - Efficacy
Increases irate excretion and decreases serum uric acid concentrations
Probenecid STEPS - Preference (Pearls)
- Ineffective in patients with even mild renal insufficiencyS -
- Start with low doses to reduce the likelihood of precipitating another gouty attack
Probenecid STEPS - Simplicity
- Coformulated with colchicine
- May cot $35-$100 per month (depending on daily dose and frequency)
Pegloticase STEP - Safety
- Contraindicated in patients with G6PD (glucose-6-phosphate deydrogenase) deficiency
- FDA black box warning regarding anaphylaxis and infusion reactions. Patients should be closely monitored for at least 2 hours after infusion, though delayed reactions have been reported.
- Risk of infusion reaction is increased when the patient’s uric acid is greater than 6mg/dl. Consider discontinuing therapy if uric acid is greater than 6mg/dL, especially if it is above this limit on two consecutive occasions
- Acute gout flare within the first 3 months of therapy
- Heart failure exacerbations have been reported in clinical trials
- Increased risk of anaphylaxis in patients who are restarting therapy after discontinuing it for greater than 4 weeks
Pegloticase STEP - Tolerability
(Gout) Bruising Chest pain Constipation Dyspnea Erthema Nausea Pruritus Urticaria
Pegloticase STEPS - Efficacy
Showed decreased uric acid concentrations and number of gout flares in clinical trials
Pegloticase STEPS - Preference (Pearls)
- Administer by intravenous infusion over 120 minutes
- Vials must be refrigerated and stored in a carton to protect them from light
- Elimination half-life is about 14 days
- Recommended to begin gout flare prophylaxis (NSAIDs or colchicine) 1 week before infusion and continue for at least 6 months
Peloticase STEPS - Simplicity
12-minute infusion (8mg) every 2 weeks
Rasburicase
- Uricolytic agent, FDA approved only for tumor lysis syndrome
- Seldom used for this indication
- Some research shows rasburicase decreases to phi and uric acid concentrations in patients with gout
