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3154 haem & MSK - nat > ic13.2, 17 gout > Flashcards

ic13.2, 17 gout Flashcards

1
Q

What is the cause of gout

A

Imbalance in purine metabolism
Adenine and Guanine converted to hypoxanthine, xanthine, uric acid

Underexcretion of uric acid

Deposition of Monosodium Urate (MSU) crystals in tissues

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2
Q

Pathogenesis of gout

A

Neutrophils phagocytose crystals
Neutrophils lyse, releasing crystals
Neutrophils release prostaglandins to recruit more neutrophils, causing a (+) feedback loop

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3
Q

Risk factors for gout (4 points)

A

Purine rich diet (red meat, seafood)

Sedentary lifestyle

Obesity

If in males < 30yo and premenopausal women → suggest inherited enzyme defect or presence of renal disease

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4
Q

Presentation of gout

A

Monoarticular (1 joint), on 1st MTP of great toe
Early morning onset, sudden
Feels like joint on fire

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5
Q

Lab test to diagnose gout

A

Must have symptoms (pain, swelling)
If asymptomatic and hyperuricemia, not considered Gout

Presence of monosodium urate crystals in synovial fluid

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6
Q

Definition of hyperuricemia

A

Males: Uric acid > 7mg/dL or 450umol/L
Females: Uric acid > 6mg/dL or 360umol/L

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7
Q

What can be used for acute flare?

A

Colchicine (1st line)
PO NSAIDs
PO Corticosteroids

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8
Q

MOA of Colchicine

A

1) Bind to tubulin, prevent tubulin polymerisation into microtubules
2) Inhibit leukocyte migration and phagocytosis
3) Inhibit leukotriene B4 and Prostaglandin production

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9
Q

Dose of Colchicine for acute flare

Dose of Colchicine in flare prophylaxis

A

Acute flare
1mg loading dose, followed by 0.5mg one hour later
OR 0.5mg BD / TDS until acute flare resolves

Flare prophylaxis
0.5mg OD for 3-6 months

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10
Q

Colchicine SE and how (3 points)

A

Nausea, Vomiting

Diarrhea
Colchicine inhibits cell division at higher doses eg. GI cells
Reducing Colchicine dose should reduce diarrhea SE

Muscle weakness
Tubulin inhibition → Affect transport of growth factors along nerves to muscles

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11
Q

Does Colchicine need dose adjustment in renal or hepatic impairment

A

renal

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12
Q

What are the indications for Colchicine (2 points)

A

1) For acute flare, should be used within 24 hours!
If (+) feedback start, Colchicine will not be useful

2) Prophylaxis against acute flares (ie. taking Colchicine with ULT to prevent acute flare)

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13
Q

MOA of NSAID or Coxib in gout

A

Inhibit prostaglandins and urate crystal phagocytosis

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14
Q

Which NSAID should not be used in gout? Why?

A

Aspirin, as it has anti-uricosuric effect (reduce uric acid excretion, increase uric acid reabsorption in kidney)

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15
Q

What does uricosuric mean

A

Increase uric excretion via kidneys, reduce uric acid reabsorption

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16
Q

Contraindication of NSAID

A

Contraindicated in CrCl < 30ml/min

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17
Q

Principles of treating acute gout flare (3 points) eg. When to start ULT

A

If on ULT during flare, continue ULT (eg. Allopurinol) during flare

Stop Colchicine after flare resolves

If starting ULT, wait 2-4 weeks after flare resolve (as ULT can worsen flare)
Unless flare is too frequent or patient feels motivated to start therapy, then dont need wait for 2-4 weeks to start ULT
ULT lowers serum uric acid level, causing uric acid crystals to exit the joint

18
Q

How long should prophylaxis of acute gout flare be given

Examples

A

Given with ULT

3-6 months
Colchicine 0.5mg OD
Low dose oral NSAID / Coxib, eg. Celecoxib 200mg OD
Low dose oral Corticosteroid, eg. Prednisolone 5 - 7.5mg OD

19
Q

When to start ULT? (4 points)

A

Frequent acute gout flares (≥ 2 per year)
Presence of tophi
Clinical or imaging findings of gouty arthropathy
History of urolithiasis (uric acid stones in kidney)

20
Q

Treatment target for ULT

A

Non-tophaceous gout: < 6 mg/dL (360umol/L)
Tophaceous gout: < 5 mg/dL (300umol/L)

rmb 7665
7 males, 6 females

21
Q

Dose of allopurinol

A

Start: 100mg/day
Maintenance: 300mg/day
Max: 900mg/day

22
Q

What to consider for Allopurinol

A

Risk of SJS / TEN (HLAB 58:01)
Lower Allopurinol dose in renal impairment

23
Q

Indication of Allopurinol

A

First line
For patients with major CVD / MACE (hence cannot take Febuxostat)

24
Q

Counselling for Allopurinol

A

Look out for flu-like symptoms (eg. fever, body aches), skin peeling, mouth ulcers, sore throat, red or sore eyes, rash

25
Q

What drugs increase risk of SCAR with Allopurinol (4 points)

A

ACEi
Ampicillin, Amoxicillin
Loop diuretics
Thiazide like diuretics

26
Q

What causes bone marrow suppression with Allopurinol (3 points)

What does Allopurinol increase adverse effect of

A

6-mercaptopurine
Azathioprine
Cyclophosphamide

Pegloticase

27
Q

Side effect of Febuxostat and Allopurinol

A

N/V
Diarrhea
DRESS symptoms (Fever, sore throat, skin rash)
Hepatotoxicity (Dark urine, Jaundice)

28
Q

Dose of Febuxostat

Indication of Febuxostat

A

40 or 80mg OD

Use if Allopurinol is CI eg. tested positive for HLAB 58:01

29
Q

What are the conditions to think of for each ULT

A

Allopurinol → SCAR
Febuxostat → use in caution with MACE
Probenecid → CKD < 50 ml/min

30
Q

MOA of Probenecid

A

URAT1 and GLUT9 inhibitor
Increase proximal tubule urate anion transport → Inhibit uric acid reabsorption → Increase uric acid excretion
Make patients excrete uric acid through kidneys

31
Q

Dose of Probenecid

A

Start: 250mg BD for 1 week
Maintenance: 2g a day

32
Q

Contraindications with Probenecid

A

Dont use in CrCl < 50ml/min
Contraindicated in urolithiasis (uric acid kidney stones)

33
Q

Counselling points with Probenecid

A

Stay hydrated eg. 2L water a day to minimise uric acid kidney stone formation
Take alkalinising agents eg. Potassium Citrate to keep urine pH > 6 to reduce uric acid kidney stone

34
Q

What is the difference between SJS/TEN and DRESS

A

DRESS - Drug Reaction with Eosinophilia and Systemic Symptoms
More systemic than SJS/TEN
Rash, Fever, Multiorgan failure

35
Q

Risk factors for SCAR (4 points)

A

CrCL < 60ml/min (moderate renal impairment)
Thiazides
HLAB 58:01
Rapid escalation of allopurinol dose

36
Q

what is the gene for allopurinol? when is genotyping indicated for allopurinol?

A

HLAB 58:01
Genotyping only recommended for patients with risk factors of renal impairment and old age
Carriers of HLAB 58:01 should avoid initiating Allopurinol, use Febuxostat instead

37
Q

Definition of clinical remission

A

Defined as: No flares for ≥ 1 year and no tophi

38
Q

How long is the duration of treatment for gout

A

Typically lifelong
Patient can choose to stop treatment, but if gout flare comes back then need to resume

39
Q

Non pharm for gout (for acute attack, diet, lifestyle)

A

Topical ice (for acute attack)

Limit alcohol intake

Limit purine rich food
Cauliflower
Mushroom
Red meat
Durian
Peanuts
Liver

Limit high fructose corn syrup

Weight management

40
Q

Which drugs can increase the risk of gout

A

hydrochlorothiazide
Aspirin

3154 haem & MSK - nat (12 decks)

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