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Flashcards in GOUT Deck (13)
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1
Q

PATHOPHYSIOLOGY OF GOUT

A
  • 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
Q

2 MAIN STRATEGIES for Tx of GOUT

A

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

3
Q

ACUTE GOUT DRUGS

A

DRUGS THAT SUPPRESS LEUKOCYTE RECRUITMENT + ACTIVATION

1) NSAIDS
2) COLCHICINE
3) GLUCOCORITCOIDS

4
Q

NSAIDS: WHICH DRUG USED?

A
  • 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

5
Q

COLCHICINE

A

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 has been replaced by NSAIDS sorta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

6
Q

GLUCOCORTICOIDS

A

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

7
Q

ALLOPURINOL

A

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 ****_

8
Q

ALLOPURINOL ADVERSE EFFECTS

A

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

9
Q

ALLOPURINAL DRUG INTERACTIONS

A

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

10
Q

PROBENECID

A

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 **_

11
Q

SULFINPYRAZONE

A

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

12
Q

SULFINPYRAZONE DRUG INTERACTIONS

A

-inhibits WARFARIN METABOLISM

sulfinPYRAzone –> is a PYRO that’s why it inhibits the WARfarin

13
Q

RASBURICASE

A

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