GOUT Flashcards
PATHOPHYSIOLOGY OF GOUT
- gout is a metabolic disorder cahracterized by HIGH LEVELs of URIC ACID in the blood
- HYPERURICEMIA can lead to deposition of sodium urate crystals in tissues
–> Hyperuricemia does NOT always lead to gout, but gout is always preceeded by hyperuricemia
- in humans, sodium urate is the end product of purine metabolism
- the deposition of urate crystals initiates an inflammatory process
2 MAIN STRATEGIES for Tx of GOUT
1) Management of ACUTE ATTACKS of GOUTY ARTHRITIS
–> goal is to CONTROL PAIN
2) LONG-TERM MANAGEMENT of CHRONIC GOUT
–> goal is to ACHEIVE NORMAL CONCENTRATIONS OF PLASMA URATE
ACUTE GOUT DRUGS
DRUGS THAT SUPPRESS LEUKOCYTE RECRUITMENT + ACTIVATION
1) NSAIDS
2) COLCHICINE
3) GLUCOCORITCOIDS
NSAIDS: WHICH DRUG USED?
- first-line drugs for ACUTE GOUT
- INDOMETHACIN is the most popular
Note: ASPIRIN IS CONTRINDICATED, b/c it competes with uric acid for the oragnic acid secretion mechanism in the proximal tubule of the kidney
ADVERSE EFFECTS: bleeding, salt and water retention, and RENAL INSUFFICIENCY
-COX-2 selective inhibitors may decrase the risk of GI bleeding, but concerns about adverse CV effects limit their long-term use
COLCHICINE
ACUTE MANAGEMENT OF GOUT
Cole’s CINEmax experience –> he’s a dentist so has the moviestar teeth –> when cleaning teeth, uses the TUBES –> binds tubes –> inhibits polymerization of microtubules –> disrupts mobility of GRANULOCYTES –> but cole always complains about his shits –> his side effect is DIARRHEA –> has been replaced by NSAIDS sorta
MOA:
1) binds to TUBULIN, inhibiting its polymerization and preventing formation of microtubules
–> disrupts mobility of granulocytes, decreasing their migration into the affected area
2) colchicine BLOCKS CELL DIVISION by DISRUPTING the MITOTIC SPINDLE
3) Inhibits synthesis and release of leukotrienes
AEs: nausea, vomiting, abdominal pain, diarrhea
- chronic administration may cause myopathy, neutropenia, aplastic anemia, and alopecia
- should NOT be used in pregnancy
- should be used with CAUTION in patients with HEPATIC, RENAL, or CV disease
Note: NSAIDS have replaced colchicine because of the troublesome DIARRHEA associated with colchicine therapy
GLUCOCORTICOIDS
ACUTE GOUT TREATMENT
- have ANTI-INFLAMMATORY and IMMUNOSUPPRESSIVE effects
- when an acute attack of gout occurs in a single joint and is unresponsive to NSAIDS, or colchicine,
DEPOT PREPARATIONS OF A GLUCOCORTICOID can be injected directly into the site of inflammation
ALLOPURINOL
CHRONIC GOUT: AGENTS THAT DECREASE PLASMA URATE CONCENTRATION
MOA: is a PURINE analog that INHIBITS XANTHINE OXIDASE
–> facilitates the dissolution of tophi by lowering uric acid plasma concentration
-the incidence of acute attacks of gouty arthritis may increase during early months of therapy with allopurinol –> is d/t MOBILIZATION of TISSUE STORES of uric acid
–>**** an NSAID or colchicine is coadminsitered during the first 4-6 months of allopurinol therapy to red_uce the chance of an acute gout attack ****_
ALLOPURINOL ADVERSE EFFECTS
ALLOPURINOL –> see steven johnson syndrome b/c is the most PURE white names (along with AL). White people often get skin rashes/hypersensititivy reactions
- is well tolerated in most patients
- get HYPERSENSITIVITY REACTIONS, especially SKIN RASHES, are the most common adverse effects
- in rare instances the rash may progress to STEVEN-JOHNSON SYNDROME
–> all patients who develop a cutaneous reaction to allopurinol should discontinue the drug
ALLOPURINAL DRUG INTERACTIONS
1) MERCAPTOPURINE (anticancer drug) and
2) AZATHIOPRINE (immunosuppresent) are both PURINE ANALOGUES which are metabolized by XANTHINE OXIDASE
–> inhiibitoin of xanthine oxidase by allopurinal can result in TOXIC LEVELS of coadminstered mercaptopurine or azathioprine
-therefore, DOSE REDUCTION of these drugs is required
PROBENECID
URICOSURIC AGENT
PROBENICID –> is the PRO BENDER –> bends around in the kidneys and competes with the urate for transport exchanger, inhibiting urate’s absorption
- 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, thus uricosuric drugs compete with urate for the transporter, therby inhibiting its reabsorptoin
NOTE: Colchicine or NSAIDS are give nearly in the therapy to avoid precipitating an attack of gout
-probenecid should nOT be used in gouty patients with
- 1) NEPHROLITHIASIS or
- 2) with OVERPRODUCTION of URIC ACID
ADVERSE EFFECTS: KNOW THESE!!!
1) mild GI irritation
2) hypersensitivity reactions; usually mild. Serious hypersensitiviy is extremely rare –> RASH + FEVER!!!! (occurs more with this drug than sulfinpyrazone, so may ask it here)
- a liberal _fluid intake should be maintained to minimize risk of renal stones **_
SULFINPYRAZONE
URICOSURIC AGENT
- 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, thus uricosuric drugs compete with urate for the transporter, therby inhibiting its reabsorptoin
NOTE: Colchicine or NSAIDS are given early in the therapy to avoid precipitating an attack of gout
AE: KNOW THESE!!!!!
1) GI irritation
2) HYPERSENSITIVIY REACTIONS, usually a RASH WITH FEVER, occur less fequently than with probenecid
3) DEPRESSION OF HEMATOPOIESIS
4) Should NOT be used by patients with UNDERLYING BLOOD DYSCRASIAS
–> a liberal fluid intake should be maintained to minimize risk of renal stones
SULFINPYRAZONE DRUG INTERACTIONS
-inhibits WARFARIN METABOLISM
sulfinPYRAzone –> is a PYRO that’s why it inhibits the WARfarin
RASBURICASE
RASBURICASE –> comes from RASPERBERRY CASES (aspergillosis) –> oxidizes uric acid to ALLANTOIN (all ant’s all ove rthe raspberry bush)
-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 –> 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
- a recombinant versin of ASPERGILLUS URICASE is available in the US
