GOUT

Characteristics of Acute Gout

 Sudden painful and swollen joint (monoarticular).
 Elevated serum urate (uric acid) level.
 Monosodium urate crystals from the affected joint.
 Last from a few days to 2-3 weeks.

Characteristics of Chronic Gout

 More than 3 attacks/year.
 Sudden painful and swollen joints (polyarticular).
 Elevated serum urate (uric acid) level.
 Formation of tophi.
 Urate nephropathy.
 Urate nephrolithiasis (urate renal calculi).

Diagnostic Criteria for Gout (2 OF THE FOLLOWING CRITERIA ARE REQUIRED)

 At least 2 attacks of painful joint swelling with complete resolution within 2
weeks.
 Clear history or observation on podagra.
 Presence of tophus.
 Rapid response to colchicine within 48 hrs of starting treatment.
 Monosodium urate crystals in synovial fluid/tissues.

Normal uric acid levels

 Male: 3.4 - 7.0 mg/dL
 Female: 2.4 - 6.0 mg/dL

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Management of Acute Gout (target pain & inflammation)

 NSAIDs
 First-line treatment.

 Any NSAIDs can be used but avoid aspirin because aspirin may cause
urate retention, unless it is given in high dose.

 Caution: History of peptic ulcer, renal impairment, cardiac failure, HTN.

 E.g. Tab Diclofenac 50 mg TDS (i.e. 1 tab TDS)

Tab. Indomethacin 25 mg TDS (i.e. 1 tab TDS) *can up to 2 tabs TDS*

 COX-2 inhibitors
 Alternative for traditional NSAIDs, risk of peptic ulcer, traditional NSAIDs
intolerance, acute gout attack of several days duration (prolonged
course of pain-killer may be needed).

 Lesser risk of GI problems than traditional NSAIDs; but higher risk of

CVS problems.

 Caution: History of peptic ulcer, renal impairment, cardiac failure, HTN.

 E.g. Arcoxia® (Tab. Etoricoxib 90 mg or 120 mg OD) (i.e. 1 tab OD)

Celebrex® (Tab. Celecoxib 200 mg or 400 mg OD) (i.e. 1 tab OD)

 Colchicine
 Alternative for those whom NSAIDs & COX-2 inhibitors are
contraindicated.

 MOA: Reduce inflammatory to urate crystals, inhibit migration of

granulocytes/WBC into the inflamed area.

 Do not reduce uric acid production !

 Side effects: N&V, abdominal pain, diarrhoea.

 Caution: renal or hepatic dysfunction.

 Contraindicated in patient with CrCl <10 / haemodialysis

 E.g. Goutnor® (Tab. Colchicine 0.5 mg or 0.6 mg TDS)

 Take 2 tabs upon attack. After 2 hrs, take 1 tab again up to TDS.
 Max: 6mg/day
 When to stop? - when patient start to have diarrhoea.

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  Corticosteroids
 Can be considered for elderly & those with renal insufficiency, hepatic
dysfunction, cardiac failure, peptic ulcer, hypersensitivity to NSAIDs or
COX-2 inhibitors.

 No role for long-term treatment.

 E.g. IM Triamcinolone 40-80 mg/day

IM Methylprednisolone 80 mg/day
PO Prednisolone up to 0.5 mg/kg/day (taper off over 4-10 days)

Management of Chronic Gout

 Allopurinol (100 mg, 300 mg) - Zyloric®

 Hypouricemic drug.
 MOA: Xanthine oxidase inhibitor (reduce the production of uric acid).
 More superior than probenecid.
 Target serum urate level <6 mg/dL.
 Usually OD dosing; max: 900 mg/day
 Side effects: rash, bone marrow suppression, anaemia, hepatitis,
jaundice, SJS, TEN. This drug may cause drowsiness.
 Should not be started until the acute attack has settled (about 2 weeks
after the attack).
 If patient is on long-term allopurinol, the drug should not be stopped
during an acute attack (may cause rebound flares).
 There may be more frequent attacks of acute gout attack at the
initiation of allopurinol therapy (esp. First 3 months). Prophylaxis using
NSAIDs/COX-2 inhibitors/colchicine may be used.
 Colchicine prophylaxis can be continued until the patient is free from
acute attacks for 6 months OR target serum urate levels is achieved for 1
month.
 Examples of drug-drug interactions with allopurinol:
 Ampicillin - rash
 Cyclophosphamide - bone marrow suppression
 Mercaptopurine/azathioprine - increase their toxicities.
 Warfarin/theophylline - prolong their half-lives.

 Primarily excreted by kidneys, so dose adjustment is needed for renal

impairment.

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  Probenecid
 Uricosuric drug.
 Alternative to allopurinol.
 MOA: Increase excretion of uric acid in urine; reduce reabsorption of
uric acid at proximal convoluted tubules.
 Contraindicated in patients with uric acid overexcretion and
overproduction; urate nephropathy; urate nephrolithiasis (due to the
risk of crystal precipitation & stone formation).
 Contraindicated in renal impairment, where CrCl<30.
 Renal function & 24-hr urinary urate excretion must be assessed before
starting probenecid.
 Side effects: GI disturbance (hence, advise patient to take after meal);
hypersensitivity rash.
 Dosage: 0.5-1 g/day, may increase up to 1.5-2 g/day (in divided doses).
 Examples of drug-drug interactions with probenecid:
 Penicillin, salicylate – decrease tubular excretion
 Furosemide – increase its serum concentration & augments its diuretic
effect.

 Surgery (last resort)

Lifestyle Modifications
 Restrict food with high purine (Appendix 1) & alcohol.
 Consume low-fat dairy products.
 Drink more water (2-3L) *limited water intake for renal failure patients*
 Exercises.
 Achieve ideal BMI (avoid overweight/obesity).

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Management of Urate nephropathy (kidney injury due to high levels of uric acid in urine)

 Increase urine output (2-3L of water/day)

 Increase urine pH (target urine pH is 6.5-7) – urinary alkalinizer
 Potassium bicarbonate (Potcit)
 10 mEq TDS. Dilute with water
 Max: 100 mEq/day
 Sodium bicarbonate
 Up to 10g/day. Taken with water.
 Decrease urate excretion (diet restriction/take allopurinol)

Management of Urate nephrolithiasis (renal stone)

 Extracorporeal shockwave lithotripsy; percutaneous nephrolithotomy (for

intrarenal stone between 5-15 mm or complex staghorn stones).
 Chemolysed using potcit or sodium bicarbonate (via oral ingestion/direct
irrigation)

Extra:
Febuxostat 80 mg (Feburic®)
 Xanthine oxidase inhibitor
 Is a non-purine analogue (vs allopurinol: purine analogue)
 Studies showed that effectiveness of febuxostat is better than allopurinol.
 Dosage: 80 mg daily, may increase up to max 120 mg/day.
 CrCl<30: 40 mg/day.
 Cause higher CV risk than allopurinol (vs allopurinol: SJS, TEN, rash, bone
marrow suppression, anaemia)
 May cause drowsiness (same like allopurinol).

Benzbromarone (Lanolone® - allopurinol 100 mg + benzbromarone 20 mg)

 Uricosuric agent (same as probenecid).
 MOA: Increase excretion of uric acid in urine; reduce reabsorption of uric acid
at proximal convoluted tubules.
 Dosage: 50-200 mg/day
 May cause liver damage.
 The therapeutic combination of benzbromarone and allopurinol significantly
decreased serum urate levels in patients with gout when compared to the
individual use of each of these agents. This finding is especially important in
treating patients who cannot control hyperuricemia with monotherapy.

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Examples of OTC/supplements for gout?

 Ascentia Uricis - similar to Allopurinol, feboxostat (2 caps BD)

 Ural (1 sac TDS)

 Opceden Go-Ezy (1 sac OD)

 Roots Noni Enzyme extracts - flush off uric acid (1 measuring cup ON)