Why take NSAID or Colchicine while taking Allopurinol?
-allopurinol has the paradoxical effect of inducing an acute gout attack.
why is probenecid contraindicated in pts with kidney disease or are overproducers of uric acid?
they are more likely with probenecid to produce uric acid stones in their kidney
this gout drug has interactions with 6-MP and azathioprine. why?
-as a xanthase oxidase inhibitor, it inhibits purine metabolism. 6-MP (azathioprine is its produg) is a purine analog, so allopurinol increases risk of 6-MP toxicity.
-GI symptoms! nausea, vomiting, diarrhea, pain.
-occurs because rapidly growing GI cells are affected
-prevent primary hyperurecemia of chronic gout
-however, not in pts with kidney disease or overproducers of uric acid because they are more likely to produce uric acid stones in the kidney
When would you use steroid over NSAID in gout patient?
When NSAIDS are contraindicated in the patient (eg stomach ulcers)
-converts uric acid to allantoin, which is excreted.
-refractory chronic gout
-why do certain drugs interact with it?
1. active form is metabolized by CYP3A4
2. it is a substrate for P-glycoprotein pump
-drugs that interact with either will increase colchicine to toxic levels.
If your patient presents with gout, what 2 common drugs he might already be using do you tell him to stop taking?
1. aspirin (low doses decrease renal urate excretion)
2. HCTZ (thiazaide diuretics decrease renal urate excretion)
-therapeutic uses (2)
1. acute gout attacks (use within hours)
2. chronic gout prophylaxis
-adverse effects (3)
-infusion site reactions
-immune response: body may make Ab against PEG porion of drug
This gout drug is metabolized by P450 and p-glycoprotein
So, drugs that block CYP3A4 or P-gp transport can increase colchicine to toxic levels
Why is colchicine not the drug of choice in tx of gout?
Strong adverse GI effects
Why is aspirin contraindicated in gout?
At low doses, aspirin inhibits uric acid secretion
-antimitotic--arrests cell in G1 by interfering with microtubule formation
-in gout, colchicine binds to microtubules in neutrophils, inhibiting their activation/migration and inflammatory response
-increases renal urate excretion
-competes with OAT (which normally reabsorbs urate)
-ineffective in pts with renal sufficiency
-contraindicated in pt with uric acid kidney stones
2. acute gout attack (paradoxical!)--allopurinol mobilizes tissue stores of uric acid. So, give drug with NSAID or colchicine
-inhibits terminal steps in uric acid synthesis
-blocks xanthine oxidase
-xanthine oxidase inhibitor, just like allopurinol
-more potent than allopurinol