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54 Finals > IC17 Gout > Flashcards

IC17 Gout Flashcards

1
Q

Disease caused by…

A
  • imbalances in purine metabolism
  • deposition of monosodium urate (MSU) crystals in articular and periarticular tissues
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2
Q

Types of gout syndrome

A

Heterogenous clinical spectrum of disease
- Recurrent acute gouty arthritis — a/w urate crystals in synovial fluid
- Tophi — deposits of MSU crystals in tissues in and surrounding joint
- Interstitial renal disease — gouty nephropathy
- Uric acid nephrolithiasis — uric acid kidney stones

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3
Q

Risk factors

A
  • Rich, developed countries
  • A/w dietary and lifestyle factors linked to obesity: alcohol, sugar drinks, red meat, sedentary lifestyle
  • Obese individuals > non-obese
  • Male > female (but gender gap narrows after menopause)
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4
Q

Occurence in male <30 yo and premenopausal women suggests

A

inherited enzyme defect or presence of renal disease

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5
Q

pathophysiology

A
  • Overproduction of uric acid
  • Under-excretion of uric acid: contributes to 90% of gout cases
  • Increase uric acid → deposition of urate crystals in periarticular fibrous tissue of synovial joints
  • Uric acid is less soluble at lower temperature → most common site of MSU crystals deposition is in BIG TOE
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6
Q

Drug/diet induced urate overproduction

A

excessive ethanol/ dietary purine/ fructose ingestion, cytotoxic drugs

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7
Q

Drug/diet induced decrease uric acid clearance

A

diuretic (thiazide/loop diuretics), cyclosporine and tacrolimus, low dose aspirin, ethambutol, pyrazinamide, ethanol, levodopa, laxative abuse, salt restriction, nicotinic acid

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8
Q

Presentation of gout attack

A
  • Usually: monoarticular @ 1st MTP of big toe
  • Wakes up from sleep by pain
  • Severe pain for several hours (joints on fire)
  • Joint is red, hot, swollen and tender
  • Sudden onset, swelling and discomfort continues days to weeks thereafter
  • Self-limiting but usually need pain relief
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9
Q

Asymptomatic hyperuricemia alone = gout?

A

NO (no tx needed)

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10
Q

Dx based on

A

Dx based on presence of MSU crystals in:
- synovial fluid (detected in joint aspirate) → confirmatory diagnosis for gout
- tissues sections of tophaceous deposits

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11
Q

When does presence of tophi and joint damage usually occurs?

A

after a long period of time. tophi causes joint damage

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12
Q

Stages of gout

A
  • Asymptomatic hyperuricemia → no pharmacotherapy
  • Acute gout (1st attack): acute arthritis, typically 1st MTP, excruciating pain → colchicine, NSAIDs, corticosteroids
  • Inter-critical phase (btw flares) → no pharmacotherapy
  • Chronic gout: hyperuricemia, development of tophi, recurrent attack of acute gout → allopurinol, febuxostat, probenecid
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13
Q

Tx goal

A
  • Provide rapid, SAFE and effective pain relief
  • Reduce future attacks (reduce serum urate concentration)
  • Address associated comorbidities
  • Prevent joint destruction and tophi formation
  • Increase QOL
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14
Q

Management of acute flares

A
  • Colchicine (best) (within 12-24hrs)
  • Oral NSAIDs/ coxib
  • Oral corticosteroids
  • IA corticosteroids (if cannot take PO meds)
  • IL-1 inhibitor (last line)
  • Can use combination tx but avoid NSAID + steroid
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15
Q

If already on ULT, what to do with ULT during acute gout flare?

A

If already on ULT, continue ULT during flare

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16
Q

Colchicine dosing

A
  • 1mg loading dose, 0.5mg one hour later (day 1)
  • subsequent 0.5mg BD/ TDS
  • after 3rd day try another agent
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17
Q

SE with colchicine

A

GI SE: nausea, vomiting, diarrhoea (SE increase with higher doses or longer duration of use)
- diarrhoea is a dose limiting SE of colchicine

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18
Q

Renal dose adjustment with colchicine

A

CrCL <30 ml/min → Initial dose: 0.3 mg/day; caution when titrating

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19
Q

can start ULT during acute attack? when start?

A

Initiate ULT (if indicated) after resolution of sx (~2-4 weeks), not during acute attack
- Also possible to consider ULT w/o waiting for flare to resolve: reduce risk of pt not returning for tx, pt high motivated for tx, pt with frequent gout attacks

20
Q

criteria to start ULT (4)

A
  • Frequent acute gout flares (≥2 per year)
  • Presence of any tophus
  • Clinical or imaging findings of gouty arthropathy/ joint damage
  • Hx of urolithiasis (kidney stones)
21
Q

ULT tx target: based on serum uric acid levels

A
  • Non-tophaceous gout: <360 µmol/L (6mg/dL)
  • Tophaceous gout: <300 µmol/L (5mg/dL)
22
Q

Eg of ULT drugs

A
  • Xanthine oxidase inhibitor: allopurinol (1st line), febuxostat
  • Uricosuric agent: probenecid
23
Q

MOA of allopurinol/ febuxostat

A

decrease uric acid synthesis

24
Q

Dosing of allopurinol

A

Start slow, go slow to reduce acute flares

  • initiation ≤100 mg/day [start with lower dose in CKD stage >3 eg <50mg/day]
  • Usual maintenance dose: >300mg/day;
  • max: 800-900mg/day
25
Q

dosing adjustment for allopurinol in renally impaired

A

start with lower dose in CKD stage >3 → <50mg/day

26
Q

SE of SCAR and when is the onset

A

Risk of SCAR (SJS/TEN/DRESS): occurs within first few weeks to months after tx initiation

27
Q

sx of SCAR (SJS/TEN/DRESS)

A
  • SJS/TEN: fever, necrosis & sloughing of epidermis
  • DRESS: rash, fever, multi-organ failure (liver, kidney, heart, lungs affected)

Pt counselling
- Flu-like sx: fever, body aches, feeling unwell
- Mouth ulcers, sore throat
- Red or sore eyes
- Rash

28
Q

Risk factor for allopurinol induced SCAR/hypersensitivity rx

A
  1. Renal impairment
  2. Agent concomitant use eg diuretic
  3. Starting dose — high starting dose
  4. HLA-B*5801 allele
  5. Escalation too rapidly
  6. Seniority — old age
29
Q

when to do HLAb8501 testing when using allopurinol?

A

HLA-B*5801 testing more useful in pt already at higher risk of allopurinol-induced SCAR eg renal impairment or older age
- SCAR reaction can still occur even without the allele
- Genotyping test has a low positive predictive value

30
Q

Pt counselling for SCAR

A
  • Generally affects skin, eye and mouth
  • Uncommon, not possible to know who will develop SCAR
  • Look out for S/S esp in the first 3 mths after initiation
    • Flu-like sx: fever, body aches, feeling unwell
    • Mouth ulcers, sore throat
    • Red or sore eyes
    • Rash
31
Q

DDI: drugs that increase hypersensitivity/toxicity of allopurinol

A
  • ACEi
  • Loop diuretics
  • Thiazide diuretics
  • Ampicillin/amoxicillin
32
Q

DDI: Allopurinol cause increased conc of these drugs -> increasing bone marrow suppression

A

MAC
- 6-mercaptopurine
- azathioprine
- cyclophosphamide

33
Q

DDI: Allopurinol cause incr [ ] of:

A

CWT
- carbamazepine
- warfarin
- theophylline

34
Q

DDI: Allopurinol cause incr AE/toxic effect of

A

pegloticase (risk X)

35
Q

Febuxostat dosing

A

initiation ≤40mg/day, titration 80mg/day if tx target not met after 2-4 weeks

36
Q

caution use of febuxostat in

A

HF and CHD

37
Q

Probenecid dosing

A

500-3000 mg/day

  • initiation 250mg BD x1 week, then 500mg BD
  • Titration: 500mg every 4 weeks as tolerated if sx not controlled
  • Usual maintenance: ≤2g/day
38
Q

SE and CI of probenecid

A

SE: hemolytic anemia
CI: urolithiasis
- Not effective in CKD, not recommended if CrCl <50ml/min

39
Q

Advice for using probenecid

A
  • keep hydrated (≥2L) of water to prevent kidney stones from forming
  • keep urine pH <6.0 (give alkaline eg potassium citrate)
40
Q

non pharm for gout

A

ice -> alleviate pain

41
Q

prophylaxis tx against gout flares tx:
drugs + duration

A

ULT + anti-inflammatory prophylaxis

  • Colchicine 0.5mg OD
  • Low dose oral NSAID/coxib (eg celecoxib 200mg OD)
  • Low dose oral corticosteroid (eg prednisolone 5-7.5mg OD)

Duration: 3-6mths

42
Q

Tx duration for ULT and define clinical remission

A
  • Clinical remission = no flares for ≥1 year and no tophi
  • If therapy is well tolerated and not burdensome, pt can have preference to continue or stop tx → shared decision making
43
Q

Non-pharm to reduce risk of flares

A
  • Limit alcohol intake
  • Limit purine rich foods (eg seafood, red meat)
  • Limit high fructose corn syrup
  • Weight management
44
Q

Eg of purine rich foods

A
  • asparagus, cauliflower, mushroom, red meat, anchovies (ikan bilis), durian, peanuts, organ meat (eg liver)
  • oatmeal, meat extracts, salmon, herring, mackerel, prawn, sardines, fish roe, cockles, mussels, scallops, strawberry, bean cake
45
Q

medication review

A
  • Switch hydrochlorothiazide to alternative antihypertensive → HCTZ decrease urate excretion
  • Use lorsartan preferentially as antihypertensive → ACEi (enalapril, captopril) and ARB (lorsartan) has uricosuric effects
  • Do NOT stop low dose aspirin therapy if indicated (despite aspirin having anti-uricosuric effects — increase urate reabsorption)
  • Do NOT add/switch cholesterol-lowering agent to fenofibrate (despite uricosuric effects)

54 Finals (7 decks)

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