Gout Flashcards
1
Q
2 main strategies for the treatment of gout:
A
- Management of acute attacks of gouty arthritis
- Long-term management of chronic gout.
2
Q
AGENTS THAT SUPPRESS LEUKOCYTE RECRUITMENT AND ACTIVATION
A
- NSAIDs
- COLCHICINE
- GLUCOCORTICOIDS
3
Q
NSAIDs for Gout Rx
A
- First-line drugs for acute gout.
- Indomethacin is the most popular.
- Other NSAIDs are also effective.
- Aspirin is contraindicated, because it competes with uric acid for the organic acid secretion mechanism in the proximal tubule of the kidney.
Adverse
- Bleeding, salt and water retention, and renal insufficiency.
- COX-2 selective inhibitors may decrease the risk of GI bleeding, but concerns about adverse CV effects limit their long-term use.
4
Q
AGENTS THAT LOWER PLASMA URATE CONCENTRATION
A
AGENTS THAT DECREASE URIC ACID SYNTHESIS: ALLOPURINOL
AGENTS THAT ENHANCE URIC ACID EXCRETION (URICOSURIC AGENTS)
- PROBENECID
- SULFINPYRAZONE
AGENTS THAT ENHANCE URIC ACID METABOLISM: RASBURICASE
5
Q
A
6
Q
ALLOPURINOL
A
- Purine analog.
- Inhibits xanthine oxidase.
- An NSAID or colchicine is coadministered during the first 4-6 months of allopurinol therapy to reduce the chance of an acute attack of gout.
Adverse
- Well tolerated by most patients.
- Hypersensitivity reactions, especially skin rashes, are the most common adverse reactions.
- In rare instances the rash may progress to
- Steven-Johnson syndrome.
- All patients who develop a cutaneous reaction to allopurinol should discontinue the drug.
Drug interactions
- anticancer drug mercaptopurine and the immunosuppressant azathioprine are purine analogues which are metabolized by xanthine oxidase.
- Inhibition of xanthine oxidase by allopurinol can result in toxic levels of coadministered mercaptopurine or azathioprine.
- Therefore, a dose reduction of these drugs is required.
7
Q
URICOSURIC AGENTS
A
- Urate is filtered, secreted, and reabsorbed by the kidneys.
- Reabsorption predominates: the amount excreted is 10% of that filtered.
- This process is mediated by a specific transporter.
- The transporter exchanges urate for an anion.
- Uricosuric drugs compete with urate for the
- transporter, thereby inhibiting its reabsorption.
8
Q
PROBENECID
A
- Colchicine or NSAIDs are given early in the therapy to avoid precipitating an attack of gout.
- Probenecid should not be used in gouty patients with nephrolithiasis or with overproduction of uric acid.
Adverse
- Mild GI irritation.
- Hypersensitivity reactions; usually mild. Serious hypersensitivity is extremely rare.
- A liberal fluid intake should be maintained to minimize risk of renal stones.
9
Q
SULFINPYRAZONE: ADVERSE EFFECTS
A
- GI irritation.
- Hypersensitivity reactions, usually a rash with fever, occur less frequently than with probenecid.
- Depression of hematopoiesis.
- Should not be used by patients with underlying blood dyscrasias.
- A liberal fluid intake should be maintained to minimize the risk of renal stones.
Drug Interactions
- Sulfinpyrazone inhibits warfarin metabolism.
10
Q
RASBURICASE
A
- AGENTS THAT ENHANCE URIC ACID METABOLISM
- Most mammals other than humans express the enzyme uricase.
- This enzyme oxidizes uric acid to allantoin, a soluble compound that is easily excreted by the kidney.
- In cancer chemotherapy, the rapid lysis of tumor cells can release free nucleotides and increase plasma urate levels.
- This can lead to massive renal injury.
- Exogenous uricase can reduce plasma urate levels and prevent renal damage.
- Allopurinol can also be used to prevent this component of tumor lysis syndrome.