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Gout Flashcards

1
Q

What should you know about uric acid?

A

end product of purine metabolism
has no functional role
some lack the uricase enzyme necessary to metabolise
overproduction or under-excretion (hyperuricemia)

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2
Q

Definition of hyperuricemia

A

a serum uric acid concentration over 420 umol/l
solubility of uric acid decreases with lower temperatures

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3
Q

How to figure out the patient overproducing or under-excreting?

A

place person on purine free diet for 3-5 days
- measure amount of uric acid in urine in 24 hours
on a regular diet
- excretion of > 1000 mg/24h = overproducer
less then 1000 mg/24 h = underexcretion (assuming high serum uric acid)

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4
Q

List the four clinical phases of gout

A

Asymptomatic hyperuricemia

Acute gouty arthritis

Intercritical gout

Chronic tophaceous gout

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5
Q

Describe asymptomatic hyperuricemia

A

elevated uric acid levels (+420 umol/l) with no sx
majority do not require drug tx

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6
Q

Describe acute gouty arthritis

A

caused by precipiation of uric acid crystals in joint space
- immune system involvement -> vasodilation -> increased permeability

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7
Q

List some characterization of acute gouty arthritis

A

pain
erythema
limited range of motion
swelling of joint

self-resolves in 7-14 days

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8
Q

List some possible triggers acute gouty arthritis

A

trauma or surgery
starvation
fatty food binge
dehydration
drugs - including urate-lowering therapy

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9
Q

Describe intercritical gout

A

asymptomatic period between flares
initial intercritical period can last 2-10 years before recurrence

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10
Q

Describe chronic tophaceous gout

A

tophi are uric acid deposits
uncommon in most
late complication of hyperuricemia
can develop at any site

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11
Q

What is the difference between RA and gout?

A

will look like RA but will be very painful and it will take years to decrease

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12
Q

Describe nephrolithiasis

A

Occurs in 10-25% of people with gout
Caused by excessive excretion of uric acid

Acidic and highly concentrated urine  precipitation

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13
Q

Describe urate nephropathy

A

Acute - massive precipitation of uric acid crystals in nephrons
Chronic - microtophi form in kidneys

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14
Q

What are some factors in the point scale for the diagnosis of gout?

A

Male (2)
Previous similar flare (2)
Rapid onset within one day (0.5)
Joint redness (1)
Toe involved (2.5)
Presence of HTN or CVD (1.5)
High serum urate (3.5)

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15
Q

List some of the goals of therapy of gout

A

Terminate an acute attack
Prevent recurrent attacks
Prevent long-term complications
Treat modifiable risk factors

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16
Q

What is the main options for acute gout flare?

A

NSAIDs
corticosteroids
colchicine
combo

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17
Q

What should you know abou NSAID use in acute gout flares?

A

high doses for first 24-72 h, then find lowest effective dose
usual NSAIDs precautions apply
may be used in combination with other acute options
consider adding GI protection (maybe add PPIs)

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18
Q

When should you stop the NSAID after an acute gout flare?

A

only stop nsaid after 2-3 sx free days

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19
Q

Efficacy and safety for NSAIDs during acute got flare

A

will significantly reduce symptoms in majority of patients
Speeds resolution
Likely comparable in efficacy to corticosteroids and colchicine
More ADR than corticosteroids, but less than colchicine

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20
Q

What should you know about corticosteroids use for acute gout flare?

A

an alternative first line choice
prednisone most commonly used
can be given PO, intra-articular, IV or IM
limited by how often should be used

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21
Q

What should you know about intra-articular steroid injection using for acute gout flare?

A

Preferred option if access to experienced physician and only 1-2 affected joints
Works faster and with less side-effects than other options
Limit to one joint 4x/year

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22
Q

List some efficacy and safety for steroids in acute gout flares?

A

As efficacious as NSAIDs and colchicine
Likely the best tolerated
Serious side-effects unlikely with episodic use

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23
Q

What are some cautions to think about for steroids and acute got flares?

A

Flare accompanied by fever, chills or other systemic symptoms
Diabetic
Excessive previous use of steroids

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24
Q

MOA of colchicine

A

Inhibits WBC motility in joint space  reduces inflammation
May also prevent deposition of urate in synovial fluid

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25
Onset of effect for colchicine
Should only be initiated if within 24h of flare May abort attack within 2-3 days Significant improvement in 24h
26
What is the optimal dosing for colchicine?
Day 1: Give 1.2mg, then 0.6mg in 1 hour (1.8mg total) Continue with 0.6mg OD or BID thereafter until resolved (~7-10 days)
27
Do you have dosing adjustments for renal impairment and colchicine?
Yes for anything under 80 ml/min
28
DDI for colchicine
Taking moderate or strong 3A4 OR P-GP inhibitors If concurrent renal / hepatic impairment  contraindicated Otherwise, use lower dose regimen: 0.6mg, then 0.3mg 1h later; do not repeat for 3 days
29
Common S/e of colchicine
GI -> nausea, vomiting, diarrhea fatigue
30
Serious s/e of colchicine
hematologic abnormalities myopathy / rhabdomyolysis
31
CI for colchicine
Pgp or 3A4 inhibition in the presence of renal or hepatic impairment Serious GI, hepatic, renal or cardiac disease
32
Efficacy and safety for colchicine
No rigorous comparative trials available Likely similar efficacy to NSAIDs or steroids, perhaps faster onset If used in low-dose regimens in proper patients, excellent safety Usually less tolerated vs. other options
33
List some combo options for acute gout flare
Colchicine + NSAID Colchicine + Steroids Intra-articular steroid + NSAID or oral steroid or colchicine NOT NSAID and STEROIDS
34
What to consider when selecting medication for acute gout flare?
Patient comorbidities (e.g. CKD, CVD, ulcers/GI issues, diabetes) Other medications Gout history Total flare number Rate of recurrence Previous medication use experience Duration of flare Number of affected joints
35
Candidates for gout prophylaxis
History of complicated kidney stones or renal insufficiency (<60ml/min) Very high serum uric acid (>800 umol/L) even if asymptomatic Radiographic damage, tophi >1 severe acute attack >2 attacks/year
36
Patients who do not need prophylaxis for gout
Mild first episode Infrequent flares and adequate response to acute therapy Infrequent flares and low serum uric acid Asymptomatic hyperuricemia if <800 umol/L and no significant risk factors
37
List some goals for gout prophylaxis
Prevent flares Halt joint destruction and tophi development Slowly lower serum urate to <300-360 umol/L
38
What should you know about colchicine or NSAIDs as ppx for gout?
Main role: prevent flares during initiation of other prophylactic agents Does not correct hyperuricemia or prevent tophi typical duration is 3-6 months - depends on serum urate values
39
List some hyperuricemic drugs
Probenecid (not currently available in Canada) Sulfinpyrazone
40
Onset of uricosuric agents
both being lowering serum urate immediately
41
Common s/e of uricosuric agents
Rash GI upset Headache Precipitation of gout flares
42
Serious s/e for uricosuric agents
Nephrolithiasis (kidney stones) Sulfinpyrazone: bleeds
43
CI for uricosuric agents
Patients on ASA -> blocks it from working CrCl <60ml/min History of kidney stones Initiation during an acute flare
44
DDI for uricosuric agents
Both increase concentration of drugs primarily relying on renal excretion NSAIDs Loop diuretics Beta-lactam antibiotics Quinolones Methotrexate Theophylline Sulfonylureas
45
Efficacy data for uricosuric agents
Similar efficacy to other hyperuricemic agents ~1/3 of patients achieve target uric acid levels Higher rates of common / serious side effects Only used when other agents failed or not tolerated
46
List some xanthine oxidase inhibitors
allopurinol febuxostat
47
MOA of XOI
Prevents uric acid synthesis by inhibiting the xanthine oxidase enzyme
48
Best to use XOI in ...
Over-producers Chronic tophaceous gout History of renal stones or renal dysfunction Frequent or severe attacks
49
Onset of XOI
max effect on uric acid reduction in 2 weeks
50
Basic dosing info for XOI
increase allopurinol 100 mg q4w can be used in renal
51
Common s/e of allopurinol
Rash Pruritus Diarrhea Precipitating gout flare
52
Common s/e febuxostat
Nausea Arthralgia Rash Precipitating gout flare
53
What should be initiated with XOI for PPX for gout?
start an NSAID or colchicine alongside to reduce the chance of a flare (often counsel for them to use naproxen OTC if not rx for a couple of weeks)
54
Serious s/e for allopurinol
Dermatologic: morbilliform eruption, erythema multiforme, exfoliative dermatitis Hematologic: eosinophilia, agranulocytosis, aplastic anemia, thrombocytopenia Hepatic toxicity Renal toxicity
55
List some risk factors that increase serious s/e for allopurinol
CKD and CVD (11x risk increase) Too-rapid titration HLA-B*5801 genotype Concomitant loop/thiazide diuretics increase risk Incidence of ~0.1-0.4% or 1 to 4 per 1000
56
Serious s/e for febuxostat
Cardiovascular risk increase Severe dermal reactions (< allopurinol) LFT increases
57
Precautions for allopurinol
HLA-B* 5801 genotype renal impairment
58
Precautions for febuxostat
High CV risk patients Hepatic impairment
59
CI for allopurinol
none
60
CI for febuxostat
Concomitant use with azathioprine or mercaptopurine
61
Main DDI to know for allopurinol
ACE inhibitor - allopurinol hypersensitivity syndrome increased loop/thiazide diuretics - allopurinol hypersensitivity syndrome increased
62
DDI with febuxostat
Concomitant use with azathioprine or mercaptopurine
63
Differences b/w allopurinol vs febuxostat
Febuxostat associated with precipitating more gout flares Febuxostat may achieve target serum urate more than allopurinol Febuxostat may reduce tophi more than allopurinol (minor) Some differences in common and serious ADRs
64
Monitoring with XOI
Serum urate every 2-5 weeks during titration Every 6 months at target Febuxostat: Additional LFTs
65
List the uricase enzyme
Includes: Pegloticase – US only Rasburicase – now available in Canada
66
MOA for uricase enzyme
converts uric acid into allantoin
67
What should you know about uricase enzyme?
Highly potent agents administered IV every 2-4 weeks Dramatic improvement in flare reduction and tophi in months Reverse complications of debilitating gout
68
Indications to use uricase enzyme for gout ppx
Indications: Other therapies contraindicated Need for rapid improvement in severe symptoms Numerous flares or tophi
69
Limitations for uricase enzymes
Antibody development extremely common Infusion reactions common Less tolerated than other options: Chest pain Severe constipation/nausea/vomiting Precipitates gout flares more often
70
When do the guidelines suggest using uricase enzyme?
use only if severe gout, if other options failed, and only use until tophi resolves
71
List some practical tips for tx for gout
Don’t worry about underexcreter vs. over-producer Watch for patients using several courses of acute flare therapy Have an early discussion about prophylactic therapy Watch for optimal dosing, timing, and titration
72
Pregnancy options for acute gout flares
Generally avoid NSAIDs in 1st and 3rd trimester Colchicine and short-courses of prednisone are likely safe
73
Pregnancy options for ppx for gout
Allopurinol likely safe Febuxostat – limited data  avoid

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