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PHAR255 > Gout > Flashcards

Gout Flashcards

1
Q

What is gout?

A

disease resulting from deposition of monosodium urate in synovial fluids, kidney, tissues

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2
Q

What is a building block of monosodium urate?

A

uric acid

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3
Q

Describe uric acid.

A

end product of purine metabolism
no functional role
some lack the uricase enzyme necessary to metabolize
overproduction or underexcretion –> hyperuricemia

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4
Q

Describe hyperuricemia.

A

serum uric acid > 420umol/L
solubility of uric acid decreases with lower temp
precipitation may need a trigger

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5
Q

What can lead to overproduction of uric acid?

A

diet –> overconsumption, diet rich in purines
disease (obesity, hyperTGs)
drugs (diuretics, cytotoxic drugs)

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6
Q

What can lead to underexcretion of uric acid?

A

diseases (CKD, HTN, dehydration)
drugs (diuretics, ACEI/ARB, ASA, alcohol)

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7
Q

Which sex is gout more common in?

A

men
-mostly occurs later in life

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8
Q

What are the four clinical phases of gout?

A

asymptomatic hyperuricemia
acute gouty arthritis
intercritical gout
chronic tophaeus gout

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9
Q

Describe asymptomatic hyperuricemia.

A

elevated uric acid (>420umol/L) but no symptoms
<25% actually develop gout
majority do not require drug treatment
potential consequences:
-gout
-urate nephropathy
-nephrolithiasis
-CKD

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10
Q

What is acute gouty arthritis?

A

caused by precipitation of uric acid crystals in joint space
characterized by sudden onset of:
-pain, erythema, limited ROM, swelling of joint
self-resolving in 7-14 days

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11
Q

How many joints are typically affected by a first gout attack?

A

90% of first attacks involve a single joint

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12
Q

What is the joint involvement frequency?

A

toes > instep > ankle > knee > wrist > fingers

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13
Q

What are some possible triggers of acute gouty arthritis?

A

trauma or surgery
starvation
fatty food binge
dehydration
drugs

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14
Q

What is intercritical gout?

A

asymptomatic period between flares
can last 2-10 years before recurrence
period becomes shorter as disease progresses

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15
Q

When is the best time for patient education and implementation of lifestyle changes in gout?

A

intercritical gout

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16
Q

What is chronic tophaeous gout?

A

tophi are uric acid deposits
uncommon in most
late complication of hyperuricemia

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17
Q

Where does tophaeous gout develop?

A

any site
-most common: hands, feet

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18
Q

What are the consequences of tophaeous gout?

A

joint deformity
surrounding tissue damage
joint destruction and pain
compresses nerves
nephrolithiasis and urate nephropathy

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19
Q

What are some renal complications of gout?

A

nephrolithiasis
-excessive excretion of uric acid
-acidic and highly concentrated urine –> precipitation
urate nephropathy
-acute –> massive precipitation of uric acid crystals in nephrons
-chronic –> microtophi form in kidney

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20
Q

How is gout diagnosed?

A

primarily based on symptoms
baseline labs: CBC, SCr, BUN, urinalysis, serum uric acid
Xray typically not useful
may confirm by analysis of synovial fluid under microscope
point system

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21
Q

What are the goals of therapy for gout?

A

terminate an acute attack
prevent recurrent attacks
prevent long-term complications
treat modifiable risk factors

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22
Q

What are the three components of gout treatment?

A

lifestyle modification
acute attack drugs
preventative drugs

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23
Q

When should non-pharm treatment be implemented for gout?

A

during the asymptomatic or intercritical period

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24
Q

What are non-pharm strategies for gout?

A

exercise and weight loss
hydration
RICE (without the compression)
diet (limit calories in general)

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25
Q

What are some foods to avoid in gout?

A

turkey
bacon
veal
liver
beer
high fructose or corn syrup foods

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26
Q

What are the treatment options for an acute gout flare?

A

NSAIDs
steroids
colchicine

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27
Q

What is a common first-line choice for an acute gout flare?

A

NSAIDs

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28
Q

Which NSAIDs can be used for an acute gout flare?

A

any NSAID can be used
-HC indication: naproxen, ibuprofen, ketoprofen, indomethacin (not special for gout), celecoxib

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29
Q

How are NSAIDs dosed for an acute gout flare?

A

high dose for first 24-72h then find LED
-use 2-3 days post improvement

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30
Q

True or false: NSAIDs cannot be combined with other acute options during a gout flare

A

false
they can be combined

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31
Q

Describe the efficacy and safety of NSAIDs for an acute gout flare.

A

significantly reduce symptoms in majority
speeds resolution
comparable efficacy to steroids and colchicine
more ADRs than steroids, less than colchicine

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32
Q

What is an alternative first-line option for an acute gout flare, asides from NSAIDs?

A

corticosteroids

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33
Q

Which corticosteroid is commonly common used for acute gout flares? How is it dosed?

A

prednisone 25-50mg OD x 3-5 days

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34
Q

Which routes of admin are available for corticosteroids during an acute gout flare?

A

po
intra-articular
IM
IV

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35
Q

What are the tapering recommendations for corticosteroids and gout?

A

short term for first few flares: no taper
concomitant anti-infl or urate lowering therapy: unlikely need taper
long course: taper over 1-2 weeks
multiple-flare hx or short intercritical period: taper

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36
Q

When are intra-articular steroids the preferred option for an acute gout flare?

A

access to experienced physician and only 1-2 affected joints

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37
Q

What is the benefit of intra-articular steroids for acute gout flare?

A

works faster and less side effects than other options

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38
Q

How many times can a joint undergo an intra-articular injection per year?

A

4x/year

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39
Q

What is the use of parenteral steroids for acute gout flare?

A

reserved for severe flares or cant take oral meds

40
Q

When should you be cautious with corticosteroid use in an acute gout flare?

A

flare accompanied by fever, chills, other systemic sx
diabetic
excessive previous use of steroids

41
Q

Describe the efficacy and safety of corticosteroids for an acute gout flare.

A

as efficacious as NSAIDs and colchicine
likely best tolerated
serious AE unlikely with episodic use

42
Q

Which acute option has considerable ADR and toxicity?

A

colchicine

43
Q

What is the MOA of colchicine?

A

inhibits WBC motility in joint space –> reduces inflammation

44
Q

When should colchicine be initiated for an acute gout flare?

A

within 24h of flare

45
Q

What is the onset for colchicine?

A

aborts attack within 2-3 days
significant improvement within 24h

46
Q

What is the optimal dosing for colchicine?

A

day 1: 1.2mg now, then 0..6mg in 1h (1.8mg total)
-then 0.6mg OD-BID until resolved (~7-10d)
close second: 0.6mg BID x 1-3d, then 0.6mg OD until resolved

47
Q

When do we adjust the dose for colchicine?

A

renal impairment
-consider alternative acute option
hepatic impairment
-consider alt acute option if severe impairment
moderate 3A4 or P-gp inhibitor
-use lower dose
-CI if renal/hepatic impairment

48
Q

What are the common adverse effects of colchicine?

A

NVD
fatigue

49
Q

What are the serious adverse effects of colchicine?

A

hematologic abnormalities
myopathy/rhabdo

50
Q

What are the drug interactions of colchicine?

A

increased statin levels (myopathy risk)
main risk: 3A4 and P-gp inhibitors
-clarithromycin, grapefruit juice, non-DHP CCB, azoles

51
Q

What are the contraindications of colchicine?

A

3A4 or P-gp inhibitor with renal/hepatic impairment
severe GI, renal, hepatic, cardiac disease

52
Q

Describe the efficacy and safety of colchicine.

A

similar efficacy to NSAIDs or steroids, perhaps faster
excellent safety when used in low-dose regimens
less tolerated than other options

53
Q

When is combination therapy used for an acute gout flare?

A

severe flares or unresponsive to monotherapy

54
Q

What are the combination options for an acute gout flare?

A

NSAID + colchicine
steroid + colchicine
intra-articular steroid + NSAID/oral steroid/colchicine

55
Q

Who are the candidates for gout prophylaxis?

A

history of complicated kidney stones or renal insufficiency
radiographic damage, tophi
very high uric acid (>800umol/L) even if asymptomatic
>1 severe acute attack
>2 attacks/year

56
Q

Who does not need gout prophylaxis?

A

mild first episode
infrequent flares and adequate response to acute therapy
infrequent flares and low serum uric acid
asymptomatic hyperuricemia < 800umol/L and no risk factors

57
Q

What are the goals for gout prophylaxis?

A

prevent flares
halt joint destruction and tophi development
SLOWLY return serum urate < 300-360 umol/L

58
Q

How do we initiate therapy with the drugs used for gout prophylaxis?

A

initiate at low doses and titrate slowly

58
Q

What is the role of NSAIDs or colchicine in gout prophylaxis?

A

prevent flare during initiation of other prophylactic agents
-does not correct hyperuricemia or prevent tophi

58
Q

What are the options for gout prophylaxis?

A

colchicine or NSAIDs
hyperuricemic drugs:
-uricosuric drugs
-xanthine oxidase inhibitors
-uricase enzymes

59
Q

What are the doses of NSAIDs and colchicine for gout prophylaxis?

A

indomethacin 25mg BID
naproxen 250mg BID
colchicine 0.6mg 3x/wk; up to 0.6mg BID

60
Q

How long are NSAIDs or colchicine used for gout prophylaxis?

A

3-6 months

61
Q

What are examples of uricosuric agents?

A

probenecid
sulfinpyrazone

62
Q

What is the MOA of uricosuric agents?

A

increase renal clearance of uric acid

63
Q

What is the role of uricosuric agents?

A

under excretor of uric acid
-require good kidney health for efficacy

64
Q

What is the onset of uricosuric agents?

A

both begin lowering serum urate immediately

65
Q

What is the dosing and administration for uricosuric agents?

A

start low and titrate slowly
ensure adequate hydration

66
Q

What are the common adverse effects of uricosuric agents?

A

GI upset
rash
headache
precipitation of gout flares

67
Q

What are the serious adverse effects of uricosuric agents?

A

nephrolithiasis
bleeds (sulfinpyrazone)

68
Q

What are contraindications of uricosuric agents?

A

pts on ASA
CrCl < 60ml/min
initiation during an acute flare
history of kidney stones

69
Q

What are the drug interactions of uricosuric agents?

A

increased [ ] of drugs relying on renal excretion
sulfinpyrazone: antiplatelets, anticoag, phenytoin

70
Q

Describe the efficacy of uricosuric agents.

A

similar efficacy to other hyperuricemic agents
higher AE rate
only use when other agents failed/intolerated

71
Q

What are examples of xanthine oxidase inhibitors?

A

allopurinol
febuxostat

72
Q

What is the MOA of xanthine oxidase inhibitors?

A

prevent uric acid synthesis by inhibiting xanthine oxidase

73
Q

Which populations are xanthine oxidase inhibitors best used in?

A

frequent or severe attacks
chronic tophaceous gout
history of kidney stones or renal dysfunction
over producers

74
Q

What is the onset of xanthine oxidase inhibitors?

A

max effect on uric acid reduction in 2 weeks

75
Q

What are the dosing principles of the xanthine oxidase inhibitors?

A

start low and titrate slowly q4wks
can be used in renal impairment
target 300-360 umol/L

76
Q

What are the common adverse effects of the xanthine oxidase inhibitors?

A

allopurinol:
-rash
-pruritis
-diarrhea
-precipitating gout flare (use NSAID or colchicine to lower risk)
febuxostat:
-rash
-nausea
-arthralgia
-precipitating gout flare (use NSAID or colchicine to lower risk)

77
Q

What are the serious adverse effects of xanthine oxidase inhibitors?

A

allopurinol: allopurinol hypersensitivity syndrome
-dermatologic, hematologic, renal, hepatic
febuxostat: CV risk, dermal rxns, LFT increase

78
Q

What are the risk factors for allopurinol hypersensitivity syndrome?

A

CKD and CVD
too-rapid titration
HLA-A*5801 genotype
loop/thiazide diuretic

79
Q

What are the precautions for xanthine oxidase inhibitors?

A

allopurinol:
-HLA-B*5801 genotype, renal impairment
febuxostat:
-CV risk pts, hepatic impairment

80
Q

What are contraindications of xanthine oxidase inhibitors?

A

allopurinol: none
febuxostat: use with azathioprine or mercaptopurine

81
Q

What are the drug interactions of the xanthine oxidase inhibitors?

A

allopurinol:
-no enzyme influence
-ACEI (increased risk of hypersensitivity syndrome)
-diuretics (increased risk of hypersensitivity syndrome)
-warfarin
-amoxicillin
-azathioprine and mercaptopurine
febuxostat:
-no enzyme influence
-azathioprine and mercaptopurine

82
Q

Compare febuxostat and allopurinol.

A

febuxostat associated with precipitating more flares
febuxostat may achieve target serum urate more
febuxostat may reduce tophi more
differences in common and serious ADRs

83
Q

When do we use febuxostat?

A

allopurinol fails to achieve serum urate target
hypersensitive to allopurinol

84
Q

What are the monitoring parameters for the xanthine oxidase inhibitors?

A

serum urate q2-5wks during titration, q6mo at target
LFTs (febuxostat)

85
Q

What are examples of uricase enzymes?

A

pegloticase
rasburicase

86
Q

What is the MOA of uricase enzymes?

A

converts uric acid into allantoin

87
Q

What are the benefits of the uricase enzymes?

A

dramatic improvement in flares and tophi in months
reverse complications of debilitating gout
highly potent, given IV q2-4wks

88
Q

What are the indications for uricase enzymes?

A

other therapies CI
need for rapid improvement in severe symptoms
numerous flares or tophi
guidelines: severe gout, others failed, only use until tophi resolves

89
Q

What are the limitations of uricase enzymes?

A

antibody development
infusion reactions
less tolerated than other options

90
Q

Based on a guideline approach, who should be placed on urate lowering therapy?

A

> 1 subcutaneous tophi
1 flare but have infrequent flares (< 2/yr)
first flare and CKD, SU >500mmol/L, urolithiasis
AGAINST: first flare, asymptomatic hyperuricemia

91
Q

Based on a guideline approach, which ULT should be used?

A

allopurinol at low dose and titrating
concomitant anti-inflammatory agents for 3-6 months

92
Q

Based on a guideline approach, what are the primary treatment targets?

A

treat to target SU
continuing indefinitely > stopping ULT

93
Q

Based on a guideline approach, when do we consider switching ULT?

A

continued frequent flares/not at SU target despite maximum tolerated dose

94
Q

Based on a guideline approach, what is the management for flares?

A

colchicine, NSAID, steroid = 1st line
-low dose colchicine > high dose colchicine

95
Q

Describe gout management in pregnancy.

A

acute flares:
-avoid NSAIDs
-colchicine and short course prednisone likely safe
prophylaxis:
-allopurinol likely safe
-limited data for febuxostat=avoid
lactation:
-ibuprofen, prednisone, allopurinol are safe

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