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8 Cards in this Set
- Front
- Back
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What is gout
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Urate crystal deponsits in peripheral joints and peri-articular tissues
Causes 1. incr. uric acid production - OH, purine rich foods, fructose rich soft drinks, increased cell turnover 2. decreased renal excretion Risk factors: hyperuricaemia Men 10x more likely Commonest form of inflammatory arthritis in men over 40 genetic, obesity, diuretics, aspirin, cyclosporin, renal failure ACUTE - sudden onset, 1st MTP CHRONIC - tophaceous gout, nephrolithiasis |
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Uric Acid Pathway
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Purines (A, G) -> Hypoxanthine -(XO)-> Xanthine -(XO)-> Uric Acid
(XO = xanthine oxidase) |
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Treatments for Gout
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1. Lifestyle (diet + wt loss)
2. Decrease uric acid synthesis (Allopurinol) 3. Increase uric acid excretion (Probenecid) 4. Decrease leucocyte migration into joint (Colchicine) 5. Anti-inflammatory/pain relief (NSAIDS) |
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Allopurinol (MOA)
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Xanthine Oxidase Inhibition
Allopurinol is a hypoxanthine analogue 1. Allopurinol competes with Hypoxanthine for XO (competitive inhibition) 2. Allopurinol -(XO)-> Alloxanthine Alloxanthine non-competetively inhibits XO (main parmacological action) |
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Allopurinol - Pharmacokinetics, Effects and Interactions
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Chronic gout, most commonly used hypouricaemic
(bad for acute gout!!) Pharmacokinetics Oral, well absorbed, short t1/2 but alloxanthine has a long t1/2 therefore, once daily (be careful in renal insufficiency - t1/2 increased heaps) Effects decreases uric acid, urate crystals in chronic gout ADEs: (withdraw straight away) GIT Allergic reactions (fatal skin rashes) Interactions - Mercaptopurine Allopurinol increases the effect of mercaptopurine (chemo drug) |
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Febuxostat
Uricase (rasburicase) |
Febuxostat
non-purine selective inhibitor of XO currently in clinical trials Uricase (rasburicase) Catalyses conversion of uric acid to allantoin For single use in tumour lysis syndromes |
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Colchicine
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Prevents migration of inflammatory neutrophils into affected joint (MOA unclear - binds to tubulin)
Used to prevent attacks and relieve acute attacks Gut effects universal May be used chronically in lower doses Overdose = multiorgan failure |
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Other treatments
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1. Increase urinary excretion
(for underexcretors with normal renal function) - Probenecid - competes with UA for proximal tubule reuptake - URAT1 transporter inhibitors - under development 2. Urinary alkalisation - increases uric acid solubility 3. General anti-inflammatory and analgesic agents - NSAIDS - pain during acute attacks 4. Lifestyle - diet (low calorie, low alcohol, red meat, shellfish) weight loss |
