Gout Flashcards
What is the causing factor for gout?
It is a disease resulting from the deposition of monosodium urate:
- Synovial fluids
- Tissues
- Kidney
What is the pathophysiology of gout?
Building block of monosodium urate, is uric acid
Uric acid the end product of purine metabolism
Some patients lack the uricase enzyme necessary to metabolize
Overproduction or under-excretion causes hyperuricemia (over 420micromol/L)
Solubility of uric acid decreases with lower temperatures (which is why gout affects joints in the extremities)
Is uric acid rapidly renally excreted?
No, it is slowly excreted (prevents crystalization of uric acid in the nephron)
What chronic condition is gout associated with?
Obesity (a lot of food rich in fat is metabolized into uric acid)
What are the four clinical phases of gout?
- Asymptomatic hyperuricemia
- Acute gouty arthritis
- Intercritical gout
- Chronic tophaceous gout
What are the characteristics of asymptomatic hyperuricemia?
Elevated uric acid levels (usually more than 420 micromol/L) with no symptoms
Less than 25% will actually develop gout (most do not require drug treatment)
What are some characteristics of acute gouty arthritis?
Caused by precipitation of uric acid crystals in joint space (90% of first attacks involve a single joint)
Symptoms:
- Pain
- Erthyema
- Limited range of motion
- Swelling of joint
What are some triggers for acute gouty arthritis?
Any activity that can rapidly changing uric acid:
Trauma or surgery
Starvation
Fatty food binge
Dehydration
Drugs (including those that lower urate)
What are some characteristics of intercritical gout?
Initial intercritical period can last 2 to 10 years before recurrence (protracted onset of disease)
Best time for patient education and implementation of lifestyle changes
What are some characteristics of chronic tophaceous gout?
Tophi are uric acid deposits
Uncommon in most patients
A late complication of hyperuricemia
Can develop on any site (common are the feet and hands)
What are the consequences of chronic tophaceous gout?
Joint deformity, destruction, pain
Surrounding tissue damaged
Compresses nerves
Nephrolitiasis and urate nephropathy
What are some complications associated with gout?
Nephrolithiasis (Occurs in 10-25% of people with gout, caused by excessive excretion of uric acid)
Urate nephropathy
How is a gout diagnosis made?
Baseline lab tests:
- CBC
- Urinalysis and SCr
- BUN
- Serum uric acid levels
Investigate comorbidities and risk factor
What is a way to confrim diagnosis?
Analysis of synovial fluid under microscope (visual inspection for uric acid crystals)
What are the goals of treatmenrt for gout?
- Terminate an acute attack
- Prevent recurrent attacks
- Prevent long-term complications
- Treat modiable risk factors
What are the three categories of gout treatment?
- Lifestyle modification (dietary changes)
- Acute attack drugs (flare management)
- Preventative drugs (prophylaxis)
When should non-pharmacologic treatment be used alone?
Only be implemented during asymptomatic or inter-critical period
- Regular exercise and weight loss (sufficient in most patients, no significant need to actively cut out purine-rich food)
- Hydration
What are some examples of purine-rich food that should be avoided in gout patients?
Alcohol
Turkey
Veal
Bacon
Liver
High fructose of corn syrup
What are the four options for acute gout flare management?
- NSAIDs
- Corticosteroids
- Colchicine
- Combinations
Is there a clinical reason for why indomethacin is a commonly prescribed NSAID for gout?
Not really
It is used because it was first used in gout. It has similar efficacy to other NSAIDs, but increased CNS effects
What are some administration instructions for NSAIDs in gout treatment?
- Use high doses for first 24-72 hours, then find lowest effective dose
- Usual NSAIDs precautions apply
- May be used in combination with other acute options
- Consider adding GI protection (PPIs)
What is a common Naproxen dose for gout flare management?
500mg TID from Day 1 to 3
250-500mg BID from Day 4 to 6
Then stop Naproxen (do not abruptly stop Naproxen after Day 3, can cause relapse)
What is the efficacy of NSAIDs in gout treatment?
Will significantly reduce symptoms in majority of patients
Speeds resolution
Likely comparable in efficacy to corticosteroids and colchicine
More ADRs than corticosteroids, but less than colchicine
What is the role of corticosteroids in gout flare management?
An alternative first-line choice
Prednisone is most commonly used (can be given PO, intra-articular, IV, or IM)
How is prednisone dosed in gout flare management?
25-50mg OD for 3-5 days
Short term course for first few flares (no taper required)
For longer course, we taper down due to concerns about relapse when stopping corticosteroids abrupty)
What is the preferred method of administering corticosteroids?
Intra-articular steroid injection (especially if only 1 or 2 affected joints)
It works faster and with less side effects than other options (locally acting)
When is corticosteroid therapy cautioned?
- Flare accompanied by fever, chills or other systemic symptoms
- Diabetic
- Excessice previous use of steroids
What is the onset of action for colchicine?
Should only be initiated if within 24h of flare
May abort attack within 2-3 days
Significant improvement in 24 h
What is the optimal dosing strategy for colchicine?
Day 1: Give 1.2mg, then 0.6mg in 1 hour
Following days: 0.6mg BID until resolved (usually takes 7 to 10 days)
Can colchicine be reliably used in patients with renal dysfunction?
No, consider alternate flare management
What are some drug interactions associated with colchicine?
Main interaction is with 3A4 and PGP inhibitors (toxicity risk)
Statins (may increase level of statins and additive myopathy risk)
How is colchicine dosed in patients on drugs that inhibit 3A4 and PGP?
0.6mg, then 0.3mg 1 hour later, do not repeat for 3 days
What is a common side effect associated with colchicine?
GI (NVD)
Fatigue
Serious side effects:
- Hematologic abnormalities
- Myopathy/rhabdomyolysis
What are some contraindications for colchicine?
- PGP or 3A4 inhibition in the presence of renal or hepatic impairment
- Serious GI, hepatic, renal, or cardiac disease
What is the relative tolerability of colchicine?
Usually less tolerated vs. other options
What are some good therapeutic combinations for gout flare management?
- Colchicine+NSAIDs
- Colchicine+Steroids
- Intra-articular steroid+NSAID or oral steroid or colchicine
What gout flare management therapies should be avoided in CKD?
Colchicine and NSAIDs
What gout flare management therapies should be avoided in CVD?
Colchicine and NSAIDs
What gout flare managment therapies should be avoided in patients with ulcers/GI issues?
NSAIds, steroids, colchicine
Which gout flare management therapies should be avoided in diabetes?
Avoid steroids
What are some qualities that can qualify a patient for gout prophylaxis?
- History of complicated kidney stones or renal insufficiency
- Every high serum uric acid (more than 800 mircomol/L)
- Radiographic damage (tophi)
- more than 1 severe acute attack
- more than 2 attacks/year (regardless of severity)
What are some goals with gout prophylaxis?
- Prevent flares
- Halt joint destruction and tophi development
- Slowly lower serum urate to below 300-360 micromol/L
Why is slow reduction of uric acid desired in prophylactic therapy?
Any rapid changes in uric acid concentration can cause precipitation of crystals (can cause gout attack)
Do either colchicine or NSAIDs impact disease mechanism (hyperuricemia) of gout?
No, they are more for symptom control
What are the hyperuricemic drug classes?
- Uricosuric
- Xanthine oxidase inhibitors
- Uricase enzyme (last line)
What are the two types of uricosuric agents?
Probenecid
Sufinpyrazone
What is the mechanism of action for uricosuric drugs?
They improve renal clearance of uric acid (useful in patients that are under-excretors)
Are uricosuric drugs effective in renal dysfunction?
No, once GFR falls below 60mL/min, uricosuric drugs loose efficacy
What are some common side effects associated with uricosuric agents?
- Rash
- GI upset
- Headache
- Precipitation of gout flares
What are some serious side effects associated with uricosuric agents?
- Nephrolithiasis
Specific to Sulfinpyrazone: bleeds
What are some contraindications associated with uricosuric agents?
- Patients on ASA
- CrCl (less than 60mL/min)
- History of kidney stones
- Initiation during an acute flare
What are some drug interactions associated with uricosuric drugs?
- NSAIDs
- Loop diuretics
- Beta-lactam antibiotics
- Quinolones
- Methotrexate
- Theophylline
- Sulfonylureas
What are some Sulfinpyrazone-specific drug interactions?
Due to increased bleed risk
What is the relative safety and efficacy of uricosuric agents?
Similar efficacy to other hyperuricemic agents
Higher incidence of side effects, so only used when other agents have failed or not tolerated
What are some examples of Xanthine Oxidase Inhibitors?
Allopurinol
Febuxostat
What is the mechanism of action for Xanthine Oxidase Inhibitors?
Prevents uric acid synthesis by inhibiting the xanthine oxidase enzyme (useful for over-producers)
What are some patient groups that stand to benefit the most from Xanthine Oxidase Inhibitors?
- Over-producers
- Chronic tophaceous gout
- History of renal stones or renal dysfunction
- Frequent or severe attacks
What is the onset of action for Xanthine Oxidase Inhibitors?
Maximum effect on uric acid reduction in 2 weeks
How is Allopurinol dosed and titrated?
100mg OD to 800mg/day
Increase dose by 100mg every 4 weeks until uric acid levels are below 360micromol/L
Can allopurinol be dosed in renal dysfunction?
Yes
- eGFR 30-60: initial 50mg daily, max 300mg/day
- eGFR 15-30: Initial 50mg EOD, max 200mg/day
- eGFR 5-15: Initial 50mg twice weekly, max 100mg/day
- eGFR under 5: Initial 50mg weekly, max is unknown
What are some common side effects associated with allopurinol?
- Rash
- Pruritus
- Diarrhea
- Precipitating gout flare
What are some common side effects associated with febuxostat?
- Nausea
- Arthralgia
- Rash
- Precipitating gout flare
What is the most significant serious side effect associated with allopurinol?
Dermatological hypersensitivity (incidence is less than 1% of all patients)
Associated with morbilliform eruption, erythema multiforme, exfoliative dermatitis
What are some types of hypersensitivity reactions associated with allopurinol?
Dermatologic
Hematologic
Hepatic toxicity
Renal toxicity
Review slide 61
What are some risk factors associated for allopurinol hypersensitivity reactions?
- CKD and CVD (11x risk increase)
- Too-rapid titration
- HLA-B*5801 (common in Korean, Thai, and Chinese patients)
- Concomittent loop/TZD diuretics
Review slide 61
What are some serious side effects associated with febuxostat?
- CV risk increase
- Severe dermal reactions (less than allopurinol)
- LFT increases
What are some precautions for patients starting allopurinol?
- HLA*B5801 genotype (found in higher frequency in Korean, Thai, and Chinese patients)
- Renal impairment
What are some precautions associated with patients starting febuxostat?
- High CV risk patients
- Hepatic impairment
What is the contraindicated drug with febuxostat?
Concomitant use with azathioprine or mercaptopurine
What are some drug interactions associated with allopurinol?
- ACEi, Loop/TZDs (increased allopurinol hypersensitivity syndrome increased)
- Azothiprene and mercaptopurine (less severe compared to febuxostat interaction)
- Amoxicillin
- Warfarin
What xantine oxidase inhibitor is preferred for first drug tried in the class?
Allopurinol is initiated first, then substituted with febuxostat if they have issues with Allopurinol (insufficient uric acid reduction, or ADRs)
How are xanthine oxidase inhibitors monitored?
Every 2-5 weeks during titration, then every 6 months at target (lifelong drugs)
What are the two uricase enzymes used in gout treatment?
- Pegloticase
- Rasburicase (available in Canada)
What is the mechanism of action for uricase enzymes?
Converts uric acid into allantoin
What are some characteristics of uricase enzyme drugs?
- Highly potent agents administered IV every 2-4 weeks
- Dramatic improvement in flare reduction and tophi in months
- Reverse complications of debilitating gout
What is the role of uricase enzyme therapies in gout treatment?
- Other therapies contraindicated
- Need for rapid improvement in severe symptoms
- Numerous flares or tophi
- Only use until tophi resolves
What are some limitations associated with uricase enzyme drugs?
- Antibody development extremely common
- Infusion reactions common
- Less tolerated than other options (increased chest pain, severe constipation, more gout flares)
For a patient with one or more subcutaneous tophi, should treatment be initiated?
Yes, initiate urate lowering therapy
For patients with frequent gout flares (more than 2/year), should treatment be initiated?
Yes, initiate urate lowering therapy
For patients that have experienced gout flares, but are infrequent (less than 2 per year), should treatment be initiated?
Depending on patient risk factors (high dietary purine, ACEi & Loop/TZDs, HTN or CVD, high serum urate)
For patients after their first gout flare treatment, is treatment indicated?
Not at the first flare
For high-risk patients (CKD, high serum urate, urolithiasis) that had a single gout flare, is treatment recommended?
Depends on individual patient factors
For patients with aymptomatic high urate without gout flares or tophi, is treatment reccomended?
Despite higher risk with elevated serum urate, we should not initiate urate lowering therapy in these patients
Can multiple gout flare treatments be combined and used concurrently?
Yes, it is recommended and it should last for 3-6 months
Review slide 74-78 for guideline approaches to gout treatment
What is the first line gout prophylaxis drug class?
Xanthine Oxidase Inhibitors
What are some good drugs for acute gout flare management in pregnant women?
Colchicine and short-course of prednisone are likely safe
What are some good drugs for gout prophylaxis in pregnant women?
Allopurinol is likely safe
Review slide 81 for a review of gout drugs
