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PR3154 > IC 17: Approach to the Management of Gout > Flashcards

IC 17: Approach to the Management of Gout Flashcards

1
Q

What are the diseases that are classified under gout syndrome?

A
  • Recurrent acute gouty arthritis
  • Tophi
  • Interstitial renal disease
  • Uric acid nephrolithiasis
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2
Q

What are factors that predispose one to gout?

A
  • Alcohol consumption
  • Sugary beverages
  • Red meat
  • Sedentary lifestyle
  • Obesity
  • Male > female
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3
Q

What is the pathway of purine metabolism?

A
  1. Glutamine produces nucleic acids in body tissues
  2. Nucleic acids break down into guanine and adenine
  3. Guanine and adenine forms hypoxanthine
  4. Hypoxanthine forms xanthine through xanthine oxidase
  5. Xanthine forms uric acid through xanthine oxidase
  6. Uric acid gets excreted in humans
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4
Q

What are the processes that involve purine in the body?

A
  • Synthesis from glutamine and nucleic acid
  • Salvage pathway (HGPRT + PRPP) salvages guanine and hypoxanthine to form nucleic acid
  • Diet
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5
Q

What leads to gout in the body?

A
  • Over-production of uric acid (primary due to inborn erorrs of metabolism) (secondary due to conditions that increase cell turnover and purine generation)
  • Under-excretion of uric acid
  • Uric acid leads to the deposition of urate crystals in periarticular fibrous tissue of synovial joints
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6
Q

What drugs or diet factors can lead to an increase in urate production?

A
  • Excessive ethanol ingestion
  • Excessive dietary purine ingestion
  • Excessive fructose ingestion
  • Cytotoxic drugs
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7
Q

What drugs or dietary factors decreases uric acid clearance?

A
  • Diuretics (thiazides and loop diuretics)
  • Cyclosporine and tacrolimus
  • Low-dose salicylates
  • Ethambutol
  • Pyrazinamide
  • Ethanol
  • Levodopa
  • Laxative abuse
  • Salt restriction
  • Nicotinic acid
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8
Q

What is the clinical presentation of an acute gouty attack?

A
  • Usually monoarticular @ 1st MTP of great toe (coldest temperature)
  • Wakes up from sleep by pain
  • Severe pain for several hours (feels like joints are on fire)
  • Joint is red, hot, swollen and tender
  • Swelling and discomfort continues days to weeks thereafter
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9
Q

What is required for a diagnosis for gout?

A
  • Presence of monosodium urate crystals in synovial fluid, tissue sections of tophaceous deposits
  • Symptoms consistent of gout
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10
Q

What is the difference between acute gout and pseudogout?

A
  • Acute gout: presence of uric acid crystals
  • Pseudogout: presence of calcium crystals
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11
Q

What are the characteristics of joint aspirates for gout?

A
  • Yellow in colour
  • Cloudy
  • Decreased viscosity
  • WBC count of 2000-50000 cells/mm3
  • Neutrophil count >50%
  • Gram stain neg
  • Crystals positive
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12
Q

What may be observed at the joints for patients with gout?

A

Tophi in the joints

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13
Q

What is the treatment goal for gout?

A
  • Provide rapid, safe and effective pain relief
  • Reduce future attacks (reduce SU conc)
  • Address associated comorbidities
  • Prevent joint destruction and tophi formation
  • Increase quality of life
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14
Q

What are the various stages of gout?

A
  1. Asymptomatic hyperuricemia (high levels of uric acid on aspiration but no pain) (women > 6 (360); men > 7 (450))
  2. Acute gout (symptoms of gout, typically 1st MTP, excruciating pain)
  3. Inter-critical phase (asymptomatic hyperuricemia)
  4. Chronic gout (hyperuricemia, development of tophi, recurrent attack of acute gout)
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15
Q

Should a patient be treated when uric acid levels are high but they are asymptomatic ?

A

No

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16
Q

Should a patient be treated when uric acid levels are high but they are asymptomatic ?

A

No

17
Q

Which drugs can be used for acute gouty attacks?

A

To be treated soonest possible (within 24 hours)
* Colchicine
* Oral NSAIDs/coxib
* Oral corticosteroids
* Intra-articular corticosteroids
* Can use combination but not NSAID + steroid

18
Q

What is the dose of colchicine?

A
  • One-off treatment with 1mg loading dose, followed by one dose of 0.5mg one hour later OR
  • 0.5mg two to three times per day until acute flare resolves
19
Q

What should be done about ULT during acute flares?

A
  • If already on ULT, continue ULT during flare
  • Initiate ULT (if indicated) after resolution of symptoms
  • Consider ULT without waiting for the flare to resolve
20
Q

What are the non-pharm treatment for acute flares of gout?

A
  • Topical ice
  • Limit alcohol intake
  • Limit purine rich food
  • Limit high-fructose corn syrup
  • Weight management
21
Q

What are the adverse effects of colchicine?

A
  • Nausea, vomiting, diarrhoea
22
Q

How should colchicine dose be adjusted in renal impairment?

A

Consider reducing dose or increasing dose interval

23
Q

What should be done in a follow-up appointment after an acute gouty attack?

A
  • Measure serum urate level
  • Assess lifestyle and comorbidities
  • Review medications and discuss risks and benefits of long-term ULT
24
Q

What are some diet and lifestyle modifications that can be considered?

A
  • Healthy, balanced diet
  • Excess body weight or alcohol may exacerbate symptoms
25
Q

What is the criteria for ULT?

A
  • Frequent acute gout flares (two or more per year)
  • Presence of tophus
  • Clinical or imaging finding of gouty arthropathy
  • History of urolithiasis (renal stones move into urinary tract)
26
Q

What is the treatment target for ULT?

A

Non-tophaceous gout: < 360 (6)
Tophaceous gout: < 300 (5)

27
Q

What is the MOA of ULT agents?

A
  • Allopurinol, febuxostat (xanthine oxidase inhibitor) which decrease uric acid synthesis
  • Probenecid (URAT1 and GLUT9 inhibitor) which increase uric acid excretion
28
Q

What should be noted for the various ULT agents?

A
  • Allopurinol: lower dose in renal impairment, risk of SCAR, contraindicated in patients with previous hypersensitivity to allopurinol
  • Febuxostat: use with caution in HF and CHD, risk of SCAR, higher risk of death
  • Probenecid: contraindicated in urolithiasis, not effective in CKD, not recommended in renal impairment (CrCl < 50), risk of haemolytic anemia in patients with G6PD deficiency
29
Q

What dietary modifications need to be made when taking uricosuric agents?

A

Keep hydrated (>= 2L of water) to prevent kidney stones from forming

30
Q

What are the presentations of SCAR?

A
  • SJS and TEN: fever + mucocutaneous lesions leading to necrosis and sloughing of epidermis
  • DRESS: rash + fever + multiorgan failure
31
Q

What are some key factors that increase the risk of allopurinol-induced SCAR?

A
  • Renal impairment
  • Agent concomitant use of therapeutic agents like diuretics
  • Starting dose high
  • HLA B*5801
  • Escalation that is rapid
  • Seniority (old age)
32
Q

Is routine testing for HLA-B*5801 done?

A

No because of low positive predictive value, testing is more useful in patients already at higher risk of allopurinol-induced SCAR

33
Q

What are the drug interactions with allopurinol?

A
  • Increase bone marrow suppression: 6-mercaptopurine, azathioprine, cyclophosphamide
  • Increase hypersensitivity reaction/toxicity of allopurinol: ACEi, loop diuretics, thiazide/thiazide-like diuretics, ampicillin/amoxicillin
  • Monitor for: carbamazepine, warfarin, theophylline
  • Increase adverse effect of pegloticase
34
Q

What can be used for prophylaxis against acute flares (ULT initiated with anti-inflammatory prophylaxis)?

A
  • Colchicine 0.5mg OD
  • Low dose oral NSAID/coxib
  • Low dose oral corticosteroid
  • For 3-6 months
35
Q

What is the definition of clinical remission for gout?

A

No flares for >= 1 year and no tophi

36
Q

What are some examples of high purine food?

A
  • Asparagus
  • Cauliflower
  • Mushroom
  • Red meat
  • Anchovies
  • Durian
  • Peanuts
  • Organ meat
37
Q

What are some examples of high purine food?

A
  • Asparagus
  • Cauliflower
  • Mushroom
  • Red meat
  • Anchovies
  • Durian
  • Peanuts
  • Organ meat
38
Q

What medication changes can be made for patients with gout?

A
  • Switch hydrochlorothiazide to alternative antihypertensive
  • Use losartan preferentially as antihypertensive
  • Do not stop low-dose aspirin therapy if indicated
  • Do not add/switch cholesterol-lowering agent to fenofibrate

PR3154 (6 decks)

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