Flashcards in Drugs for Gout Deck (25):
Describe the clinical use for NSAIDs in gout.
They are the drug of choice for decreasing inflammation in acute gout
Discuss the adverse effects of indomethacin (NSAID of choice in gout).
It can cause adverse CNS effects in the elderly
Why is aspirin contraindicated in gout?
Low-moderate doses will decrease renal excretion of urate resulting in hyperuricemia
Describe the mechanism of action of corticosteroids.
They upregulate lipocortin to inhibit phospholipase A2 (prevents arachidonic acid mobilization) and down-regulate COX-2 in monocytes/other immune cells.
Describe the clinical use of corticosteroids in gout.
Drug of choice for decreasing inflammation in acute gout for patients who can't use NSAIDs or colchicine. Can also treat pseudogout
Describe the mechanism of action of Colchicine.
It binds beta-tubulin to inhibit microtubule polymerization thus stopping lamellipodia formation (and thus motility) of neutrophils, subsequently reducing phagocytosis of monosodium urate crystals
What adverse effects are associated with colchicine?
n/v/d, abd pain, myelosuppression
Describe the drug interactions relevant to colchicine use.
Avoid coadministration w/ strong CYP3A4 inhibitors in pts w/ hepatic impairment, or P-glycoprotein inhibitors in pts w/ renal imapirment because of life-threatening toxicity at therapeutic doses
Describe the clinical use for colchicine.
Acute and chronic gout; reduces frequency of attacks and relieves pain by reducing the attacks (NOT an analgesic). Used acutely to abort attacks. Prevents attacks in chronic gout and as initiation therapy w/ allopurinol
Why isn't colchicine considered the drug of choice for gout?
Because of its toxicity and the availability of less toxic drugs like NSAIDs
Describe the mechanism of action of allopurinol.
It inhibits xanthine oxidase (the enzyme that metabolizes purine bases to uric acid), resulting in decreased plasma and urinary urate
Describe the adverse effects associated with allopurinol.
It can increase the frequency of attacks during the first months of therapy, so it should be combined with colchicine. It can also cause hypersensitivity rxns and malaise
Name the drugs that are used to treat chronic gout.
Allopurinol, Febuxostat, Pegloticase, and Probenecid. Colchicine can be used for acute or chronic gout.
Discuss the significant drug interactions associated with allopurinol.
It interferes with CYP3A inactivation of other drugs in the liver
How is allopurinol administered and excreted?
Describe the mechanism of action of Febuxostat.
It is an even more potent xanthine oxidase inhibitor than allopurinol, preventing uric acid production
Describe the mechanism of action of Pegloticase.
It decreases plasma urate levels by increasing metabolism of uric acid to allantoin for excretion
What special population would benefit from Feboxustat?
Chronic gout patients who have renal impairment
When is Pegloticase indicated?
Chronic gout, including severe, treatment-refractory chronic gout
How is Pegloticase administered and how often?
IV, every 2 weeks for severe tx-refractory gout
Why should Febuxostat be given with NSAIDs or colchicine for the first 6 months of use?
To prevent the incidence of paradoxical gouty flares
Describe the mechanism of action of Probenecid.
It inhibits tubular reabsorption of urate by blocking URAT1, increasing excretion and it inhibits excretion of other agents like PCN
Describe the adverse effects associated with Febuxostat.
Increased CV events (MI, anemia) compared with allopurinol, but doesn't require dose reduction in renal impaired pts and has less association w/ hypersensitivity rxns
Describe the adverse effects associated with Probenecid.
GI irritation (e.g. ulcers), hypersensitivity rxns, provocation of gouty arthritis attacks, renal stones. CNS stim, convulsions, and death from resp failure in overdose.
*Probenecid -- acid -- ulcers -- dead