Drugs for Gout Flashcards
What drugs are used to treat gout?
Inhibit uric acid synthesis = allopurinol
Inhibit uric acid excretion = uricosuric agents –> probenecid, sulfinpyrazone
Inhibit leucocyte migration into the joint = colchicine
anti-inflammatory and analgesics = NSAIDs
What drugs prevent gout attacks?
Allopurinol
Probenecid
What drugs treat acute gout attacks?
Colchicine
NSAIDs - indomethacin
Corticosteroids
What is the MOA of allopurinol?
Competitive inhibitor of xanthine oxidase
Reduces the concentration of relatively insoluble urates and uric acid in tissue, plasma, and urine –> don’t commence during acute attack
How does oxypurinol influence the effect of allopurinol?
Oxypurinol (metabolite of allopurinol) is responsible (largely) for the action of allopurinol –> it remains in tissue for period of time as non-competitive inhibitor of xanthine oxidase
Describe some pk characteristics of allopurinol
Well absorbed orally
Short half-life then converted to oxypurinol
renal excretion is a balance between glomerular filtration and probenecid-sensitive tubular reabsorption
Initiated w/ NSAID
What are some notable ADRs of allopurinol?
GI disturbances
Allergic reactions (rashes)
Potentially fatal SJS and toxic epidermal necrolysis
What is the MOA of probenecid?
Weak acid –> competitively inhibits the reabsorption of uric acid by renal tubules
What are some ADRs of probenecid?
Well tolerated
Headache, nausea, frequent urination
What is the MOA of colchicine?
Prevents migration of neutrophils into the joint
Binds to tubulin —> depolymerisation of microtubules and reduced cell motility –> prevents crystal-induced joint inflammation
What are some notable ADRs of colchicine?
GI effects (n/v, abdominal pain)
Severe diarrhoea = w/ large doses
GI haemorrhage, kidney damage
Prolonged treatment causes blood dyscrasias (aplastic anaemia), rashes, peripheral neuropathies
What is the MOA of rasburicase?
Urate oxidase acts as catalyst in enzymatic oxidation of uric acid to allantoin in blood —> allatoin is readily excreted metabolite that is more soluble than uric acid
What is rasburicase?
Recombinant urate oxidase enzyme
NOT a uricosuric agent
Used in tumour lysis syndrome, sometimes aggressive gout
