6 Gout Flashcards
Gout is a disease caused by…
An increase in the amount of uric acid in the body
What are the two categories of gout patients?
Overproducers of uric acid - larger body pool of uric acid (polycythemia vera, myeloid metaplasia, leukemia, lymphoma)
Underexcretors of uric acid - renal excretion is somehow low (lead neuropathy, glycogen-storage disease, sickle cell disease)
Only _______ drugs affect uric acid
Acidic drugs
WHat are the two distinct objectives in the treatment of gout?
Terminate the inflammatory process of an acute attack
Reduce hyperuricemia to prevent formation of urate deposits and acute attacks of gouty arthritis and to promote resolution of tophi
How is termination of the inflammatory process of an acute attack of gout accomplished?
By use of colchicine, indomethacin, and other anti-inflammatory agents
How is reduction of hyperuricemia accomplished?
By uricosuric agents that reduce the pool of uric acid in tophaceous gout and secondary hyperuricemia (probenecid and sulfinpyrazone) and by allopurinol which decreases the formation of uric acid
Acute attacks of gout follow the deposition of _______ in peripheral joints
Uric acid crystals
In acute attacks of gout, uric acid crystals are phagocytosis by ________, initiating an inflammatory reaction mediated by ________ and __________
Synoviocytes
Prostaglandins and cells of the immune system
What classes of drugs are used for acute management of gout?
NSAIDs (indomethacin and others)
Colchicine
What drugs are used for chronic prevention of gout?
Uricosuric agents (probenecid)
Xanthine oxidase inhibitors (Allopurinol, febuxostat)
Enzyme converting uric acid to allantoin (rasburicase, prgloticase)
Glucocorticoids
What is the primary NSAID used in the treatment of gout
Indomethacin
Can also use Naproxen and Sulindac but Indomethacin is DOC
Can also use specific reversible inhibitors of COX-2
Which NSAIDs are CONTRAINDICATED for the treatment of gout?
Aspirin and other salicylates
They are acids so they decrease urate excretion
Colchicine is derived from …
Colchicum autumnale or the autumn crocus
MOA for colchicine
Binds to tubulin and inhibits the assembly of microtubules
Produces it’s anti-inflammatory effect by inhibiting leukocyte migration and phagocytosis —> inhibition of the formation of leukotriene B4
Colchicine has an anti inflammatory effect but no …
No analgesic effect
No effect on COX enzymes
No effect on urate excretion
How is colchicine used?
To reduce the pain and inflammation of an acute attack of gouty arthritis
Administered orally (IV has increased toxicity)
Adverse effects of colchicine
DIARRHEA**
Nausea
Vomiting
Abdominal pain
Side effects produced by the inhibition of tubulin polymerization
Drug used to reduce inflammation in acute gout by binding to tubulin —> inhibiting the assembly of microtubules
Colchicine
How do uricosuric agents work?
Increase the urinary excretion of uric acid by blocking the active reabsorption of uric acid in the proximal tubule
When using uricosuric agents, _________ should be maintained
A large urine volume
This is minimize the possibility of kidney stone formation
Also, keep the pH above 6.0 (alkali administration)
Initial administration of a uricosuric agent may trigger a gouty attack. What should you do to prevent this?
Prophylactic colchicine therapy is indicated
Are uricosuric agents effective in acute attacks of gouty arthritis?
NO
In fact, they may aggravate symptoms
Control the attack with colchicine or NSAIDs and start the uricosuric agent after they’ve recovered
Main side effect of uricosuric agents
GI irritation
When should you initiate probenecid?
2-3 weeks after an acute attack (it’s a uricosuric agent so it will exacerbate symptoms if administered DURING an attack)
