1
Q
What is gout?
A
A disease resulting from deposition of monosodium urate in:
- Synovial fluids
- Tissues
- Kidneys
(Building block of monosodium urate is uric acid)
2
Q
Overproduction or under-excretion of uric acid is called?
A
Hyperuricemia
3
Q
What is hyperuricemia defined as?
How can it occur (2)?
A
- A serum concentration over 420 mcmol/L
- Solubility of uric acid decreases with lower temps
- Precipitation may require a trigger
4
Q
What are 3 things that can lead to overproduction of uric acid?
A
- Diet –> overconsumption, rich in purines
- Disease
- Obesity
- Hypertriglyceridemia - Drugs
- Diuretics
- Cytotoxic drugs
5
Q
What are 2 things that can lead to underexcretion of uric acid?
A
- Disease
- CKD
- HTN
- Dehydration - Drugs
- Alcohol
- Diuretics
- ACEi/ARB
6
Q
If person is on a regular diet, how many mg or uric acid per 24h classifies them as overproducers or underexcreters?
A
- Excretion of >1000mg/24h = overproducer
- Less than 1000mg/24h = underexcreter (assuming high serum uric acid)
7
Q
What are the 4 clinical phases of gout?
A
- Asymptomatic hyperuricemia
- Acute gouty arthritis
- Intercritical gout
- Chronic tophaceous gout
8
Q
True or False? Majority of asymptomatic hyperuricemia requires drug treatment
A
False - do not
9
Q
What is acute gouty arthritis?
A
Caused by precipitation of uric acid crystals in joint space
- Immune system involvement –> vasodilation –> increased permeability
10
Q
Acute gouty arthritis is characterized by? (4)
How long until it resolves?
A
- Pain
- Erythema
- Limited ROM
- Swelling of joint
Often resolves in 7-14 days
11
Q
What are some possible triggers of acute gouty arthritis? (5)
A
- Trauma or surgery
- Starvation
- Fatty food binge
- Dehydration
- Drugs - including urate-lowering therapy
12
Q
What is intercritical gout? (4)
A
- Asymptomatic period between flares
- Initial intercritical period can last 2-10 years before recurrence
- Period becomes shorter as disease progresses
- Best time for pt eduation and implementation of lifestyle changes
13
Q
What are the consequences of chronic tophaceous gout? (5)
A
- Joint deformity
- Surrounding tissue damaged
- Joint destruction and pain
- Compresses nerves
- Nephrolithiasis and urate nephropathy
14
Q
Diagnosis of gout is primarily made from symptoms. But what are some good baseline lab tests to have? (4)
A
- CBC
- Urinalysis and SCr
- BUN
- Serum uric acid levels
15
Q
What are the goals of gout treatment? (4)
A
- Terminate an acute attack
- Prevent recurrent attacks
- Prevent long-term complications
- Treat modifiable risk factors
16
Q
The 3 treatment strategies for gout includes: (3)
A
- Lifestyle modification
- Acute attack drugs
- Preventative drugs
17
Q
When is the best time to implement non-pharmacologic treatment of gout?
A
During asymptomatic or inter-critical period, as lifestyle changes may precipitate or worsen a gout flare.
18
Q
What are the 2 most important non-pharmacologic treatments of gout?
A
- Regular exercise and weight loss
- Hydration
19
Q
What are some foods that should be avoided if someone has gout? (6)
A
- Alcohol (esp. beer)
- Turkey
- Veal
- Bacon
- Liver
- High fructose or corn syrup foods
20
Q
True or False? If a gout patient is going to continue to drink alcohol, we’d prefer them to drink beer over wine.
A
False - wine > beer in terms of gout
21
Q
What are the 4 options for treating an acute gout flare?
A
- NSAIDs
- Corticosteroids
- Colchicine
- Combinations
22
Q
The most common first-line choice medication for treating an acute gout flare is?
A
NSAIDs (then corticosteroids)
23
Q
True or False? Any NSAID can be used in acute gout flare treatment.
A
True
24
Q
What is the NSAID treatment strategy for acute gout flare? That is, what kind of dosing? How long? Combination meds?
A
- Use high doses for first 24-72h, then find the lowest effective dose
- May be used in combo with other acute options
- Consider adding GI protection
25
When using an NSAID to treat an acute gout flare, what is the best time for a patient to stop the medication? Why?
Stop once symptom free for 2-3 days. Otherwise the flare might come back.
26
What is the efficacy of NSAIDs for treatment of acute gout flare look like? (3)
1. Will significantly reduce symptoms in majority of patients
2. Speeds resolution
3. Likely comparable in efficacy to corticosteroids and colchicine
27
The most common corticosteroid given for acute gout flare treatment is? What formulations?
Prednisone
PO, intra-articular, IV or IM
28
What is the dosing of prednisone for the treatment of acute gout flare?
25-50mg once daily used for 3-5 days
29
When should and shouldn't we taper off a corticosteroid being used for an acute gout flare? (4)
1. If a long-course was needed, taper over 1-2 weeks
2. If multiple-flare hisotry or short inter-critical period --> taper
3. Short-term course for first few flares = no taper
4. If on concomitant anti-inflammatory or urate-lowering therapy, unlikely to need taper
30
When is an intra-articular steroid injection preferred when treating an acute gout flare?
How quick does it work?
What is the limit?
1. Preferred option if access to experienced physician and only 1-2 affected joints
2. Works faster and with less side-effects than other options
3. Limit to one joint 4x/year
31
Parenteral steroids for acute gout flare treatment. Yay or nay?
Yay kind of...reserve for severe flares or cannot take oral medications
32
What are 3 cautions for using corticosteroids in the treatment of acute gout flare?
1. Flare accompanied by fever, chills or other systemic symptoms
2. Diabetic
3. Excessive previous use of steroids
33
What is the MOA of colchicine? (2)
1. Inhibits WBC motility in joint space --> reduces inflammation
2. May also prevent deposition of urate in synovial fluid
34
What is the onset of effect of colchicine? (3)
1. Should only be initiated if within 24h of flare
2. May abort attack within 2-3 days
3. Significant improvement in 24h
35
What is the optimal dosing and administration of colchicine? (2)
1. Day 1: Give 1.2mg, then 0.6mg in 1 hour (1.8mg total)
2. Continue with 0.6mg OD or BID thereafter until resolved (~7-10 days)
36
What is an alternative, but acceptable dosing of colchicine?
0.6mg BID for 1-3 days, then 0.6mg once daily until flare resolved
37
Colchicine in hepatic impairment. Yay or nay?
Yay but have to lower the dose in severe impairment
38
Colchicine in renal impairment. Yay or nay? (3)
1. For any renal impairment: consider alternative flare management
2. CrCl <30mL/min - cautiously use standard day 1 dose; no more doses for 14 days
3. Dialysis does not remove
So overall, nay, but some yay with caution
39
When is colchicine use actually contraindicated? (2)
1. If taking a moderate or strong 3A4 OR P-GP inhibitor and if concurrent renal/hepatic impairment
2. Serious GI, hepatic, renal, or cardiac disease
40
What are the common side effects of colchicine (2)?
1. GI (N/V/D)
2. Fatigue
41
What are the 2 serious side effects of colchicine?
1. Hematologic abnormalities
2. Myopathy/rhabdomyolysis
42
What are 4 drug interactions seen with colchicine?
1. Azole antifungals
2. Clarithromycin
3. Verapamil/Diltiazem
4. Grapefruit juice
- Not a CI, but necessitates dose adjustment
43
What is the interaction between colchicine and statins?
May increase level of statins and addititve myopathy
44
Acute gout flare combination treatment is reserved for severe flares or unresponsive to monotherapy. What are the 3 common combinations?
1. Colchicine + NSAID
2. Colchicine + Steroids
3. Intra-articular steroid + NSAID or oral steroid or colchicine
45
Candidates for gout prophylaxis includes: (5)
1. History of complicated kidney stones or renal insufficiency (<60ml/min)
2. Very high serum uric acid (>800 umol/L) even if asymptomatic
3. Radiographic damage, tophi
4. ≥ 1 severe acute attack
5. ≥ 2 attacks/year
46
Patients who DO NOT need gout prophylaxis includes? (4)
1. Mild first episode
2. Infrequent flares and adequate response to acute therapy
3. Infrequent flares and low serum uric acid
4. Asymptomatic hyperuricemia if <800 umol/L and no significant risk factors
47
What are the goals for gout prophylaxis? (3)
1. Prevent flares
2. Halt joint destruction and tophi development
3. Slowly lower serum urate to <300-360 mcmol/L
48
What are the 5 gout prophylaxis medication options?
1. Colchicine
2. NSAIDs
3. Uricosuric agents
4. Xanthine oxidase inhibitors
5. Uricase enzyme
49
What is the main role of colchicine/NSAIDs in gout prophylaxis?
What do they not do?
1. Prevent flares during initiation of other prophylactic agents (bridging)
2. Does not correct hyperuricemia or prevent toci
50
Typical duration of colchicine/NSAID use in gout prophylaxis is?
3-6 months - depends on serum urate values
51
What are the 2 uricosuric agents in gout prophylaxis?
1. Probenecid (not currently available in Canada)
2. Sulfinpyrazone (also pulled recently)
52
What is required of the patient if they were to use a uricosuric agent?
Requires good kidney health for efficacy
(Increases renal clearance of uric acid)
53
What is the onset of the uricosuric agents?
Both begin lowering serum urate immediately
54
You don't need to memorize the numbers when it comes to dosing the uricosuric agents. Instead, what principle is important to know?
Start low go slow
55
When on a uricosuric agent, the patient must maintain ________ _________
adequate hydration
56
Common side effects of the uricosuric agents include? (4)
1. Rash
2. GI upset
3. Headache
4. Precipitation of gout flares
57
The serious side effects of the uricosuric agents include? (2)
1. Kidney stones
2. Sulfinpyrazone: bleeds
58
What are 4 CIs of uricosuric drugs?
1. Patients on ASA
2. CrCl < 60mL/min
3. History of kidney stones
4. Initiation during an acute flare
59
What are the DIs associated with uricosuric agents?
How about sulfinpyrazone specific?
1. Both increase concentration of drugs primarily relying on renal excretion
- NSAIDs
- Loop diuretics
- MTX
2. Sulfinpyrazone: antiplateletes/anticoagulants, phenytoin
60
Uricosuric agents are only used when?
When other agents failed or not tolerated
61
What are the two xanthine oxidase inhibitor drugs?
1. Allopurinol
2. Febuxostat
62
What is the MOA of xanthine oxidase inhibitors?
Prevents uric acid synthesis by inhibiting the xanthine oxidase enzyme
63
Xanthine oxidase inhibitors are best used in which patients? (4)
1. Over-producers
2. Chronic tophaceous gout
3. History of renal stones or renal dysfunction
4. Frequent or severe attacks
64
What is the onset of xanthine oxidase inhibitors?
Max effect on uric acid reduction in 2 weeks
65
What is the dosing principle we need to know regarding the xanthine oxidase inhibitors?
Start low go slow
66
True or False? Xanthine oxidase inhibitors cannot be used in renal impairment/dialysis.
False - can be used with dose reductions. Works in dialysis
67
What are the common side effects of allopurinol? (4)
1. Rash
2. Precipitating gout flare
3. Pruritus
4. Diarrhea
68
What are the common side effects of febuxostat? (4)
1. Rash
2. Precipitating gout flare
3. Nausea
4. Arthralgia
69
What is the big serious side effect of allopurinol?
Allopurinol hypersensitivity syndrome
70
What are the serious side effects of febuxostat? (3)
1. CV risk increase
2. Severe dermal reactions (< allopurinol though)
3. LFT increases
71
What are the precautions to using allopurinol? (2)
1. HLA-B*5801 genotype
2. Renal impairment
72
What are the precautions to using febuxostat? (2)
1. High CV risk patients
2. Hepatic impairment
73
What are the CIs of allopurinol and febuxostat? (1 point per med)
1. Allopurinol - None
2. Febuxostat - Concomitant use with azathioprine or mercaptopurine
74
What are 2 big drug interactions to know about with allopurinol?
1. ACEi's: allopurinol hypersensitivity syndrome increased
2. Loop/thiazide diuretics: same as above
75
Compare allopurinol vs. febuxostat in terms of efficacy (4)
1. Febuxostat associated with precipitating more gout flares
2. Febuxostat may achieve target serum urate more than allopurinol
3. Febuxostat may reduce tophi more than allopurinol (minor)
4. Some differences in common and serious ADRs
76
Guideline recommendation - use febuxostat if: (2)
1. Allopurinol fails to achieve serum urate target after adequate trial
2. Hypersensitive to allopurinol
77
What should be monitored while on a xanthine oxidase inhibitor? (2)
What about febuxostat specifically?
Serum urate:
- Every 2-5 weeks during titration
- Every 6 months at target
Febuxostat - additional LFTs
78
What are the 2 uricase enzyme drugs?
1. Pegloticase - US only
2. Rasburicase - now available in Canada
79
What is the MOA of uricase enzyme drugs?
Converts uric acid into allantoin
80
How often is uricase enzyme administered?
IV every 2-4 weeks
81
What is the efficacy of uricase enzyme drugs? (2)
1. Dramatic improvement in flare reduction and tophi in months
2. Reverse complications of debilitating gout
82
What are 3 indications for using uricase enzyme drugs?
1. Other therapies contraindicated
2. Need for rapid improvement in severe symptoms
3. Numerous flares or tophi
83
What are the 3 limitations to using uricase enzyme drugs?
1. Antibody development extremely common
2. Infusion reactions common
3. Less tolerated than other options:
- Chest pain
- Severe constipation/N/V
- Precipitates gout flares more often
84
What do the guidelines say when it comes to using uricase enzyme drugs?
Use only if severe gout, if other options failed, and only use until tophi resolves
85
What do the guidelines say regarding who should be placed on urate lowering therapy (ULT)?
1. Pts with 1 or more subcut tophi, initiate ULT
2. Pts with frequent gout flares (≥2/year)
86
Treatment of acute gout flares in pregnancy. What should be avoided?
What can be used?
1. Generally avoid NSAIDs in 1st and 3rd trimester
2. Colchicine and short-courses of prednisone are likely safe
87
Gout prophylaxis in pregnancy. What can be used? (2 points)
1. Allopurinol likely safe
2. Febuxostat - limited data --> avoid
88
Gout and lactation. What drugs are safe choices? (3)
1. Ibuprofen
2. Prednisone
3. Allopurinol
