Term
| What does hyperuricemia lead to? |
|
Definition
| Deposition of sodium urate (end product of purine metabolism) crystals in tissues, esp, joints and kidney. NB that hyperuricemia does not always lead to gout but gout is always preceded by hyperuricemia |
|
|
Term
| Are urate crystals inflammatory? |
|
Definition
| Yes, they initiate infiltration of granulocytes that try to phagocytize it |
|
|
Term
| What does the increased production of lactate in the synovial joints do? |
|
Definition
| It further fosters deposition of urate crystals |
|
|
Term
| What is the first line of Rxs for Acute Gout? |
|
Definition
| NSAIDs like indomethacin but not aspirin as at low doses it competes secretion at PCT. Other Rxs are Colchicine & Glucocorticoids |
|
|
Term
| What are the A/Es of NSAID use for Acute Gout |
|
Definition
| Bleeding (GI?), salt & water retention and renal insufficiency (???) |
|
|
Term
|
Definition
Works by binding to tubulin thus inhibiting polymerization to microtubules -> disrupted motility and mitotic spindles. In addition it inhibits synthesis & release of leukotrienes (!?).
Needs to be given within 1-2 days to be effective. Alleviates pain within 12hrs.
A/Es:
NVD, abdominal pain; chronic admin -> myopathy, neutropenia, aplastic anemia, and alopecia (?).
Contraindications:
Not to be used in preg and shud be used with caution in pts w/ hepatic, renal or CVS Dz.
NB that its more specific for gout then NSAIDs but are replaced by NSAIDs cause of troublesome diarrhea |
|
|
Term
|
Definition
| Used for acute polyarticular gout or when contraindications such as w/ renal insufficiency. For single joints but when NSAIDs and colchicines dont work, then inject as a depot |
|
|
Term
| What are the Rxs used to Tx Chronic Gout? |
|
Definition
Allopurinol
Probenecid
Sulfinpyrazone
Rasburicase
NB that the first one is the only one that is an agent that decreases uric acid synthesis and that the rest are Uricosuric agents (enhance uric acid excretion) |
|
|
Term
|
Definition
Purine analog, inhibits the last two steps in uric acid biosyn that are catalyzed by xanthine oxidase.
Facilitates dissolution of tophi, & prevents development or progression of chronic gouty arthritis. NB NSAIDs and colchicine are coadministered during first 4-6 mos to reduce chance of acute attack of gout. Its well tolerated in most pts. Most common A/E is skin rash (3% pts), which in rare cases may progress to Steven-Johnson syndrome, thus for this reason, anyone who develops a cutaneous rxn must discontinue.
Rx-Rx interaction: AntiCA Rx 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. Thus reduce dose |
|
|
Term
| Uricosuric Agents (increase rate of excretion of uric acid) |
|
Definition
| Urate is filtered, secreted and reabsorbed (mediated by exchange for an anion) by the kidney. Reabsorption predominates and amount exreted is abt 10% of filtered. Thus Uricosuric agents compete w/ urate at this brush-border transporter. |
|
|
Term
|
Definition
Concomitant colchicine or NSAIDs are used early on to avoid precipitating an attack of gout (occurs in 20% of pts on probenecid alone).
Contraindicated in pts w/ nephrolithiasis or overproduction of uric acid (???).
Because probenecid inhibits secretion of most anions, the dose of other drugs excreted by this pathway shud be reduced.
Low dose aspirin may antagonize probenecid axn (???).
A/Es:
Mild GI irritation thus use caution in peptic ulcer pts. Mild hypersensitivity rxns. Take alot of fluids to prevent renal stones. |
|
|
Term
|
Definition
Same MOA of probenecid but rarely used today.
More GI irritation then probenecid; hypersensitivity usually a rash w/ fever is less frequent then w/ probenecid. Depression of hematopoiesis occurs thus not to be used on pts w/ underlying blood dyscrasias. Take plenty water to prevent stones.
NB that it prevnts warfarin metabolism.
Also note that thiazide diuretics & cyclosporine impair urate excretion |
|
|
Term
|
Definition
|
|
