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MSK Pharm > Gout and Hyperuricemia > Flashcards

Gout and Hyperuricemia Flashcards

1
Q

uric acid formation and disposition

A
  • major product of purine metabolism
  • biosyn of urate via XO
  • kidney- filtered urate is reabsorbed via URAT1
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2
Q

Uric acid- description

A
  • low water solubility

- forms sharp needle-like crystals- deposited in joints, kidneys, or soft tissues

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3
Q

Hyperuricemia (necessary but not sufficient to produce gout)- factors contributing to gout attacks in the 1st metatarsal-phalangeal joint

A
  • lower T
  • low pH
  • joint dehydration
  • altered matrix proteins, exposed cartilage fragments, and nucleating debris (joint trauma)
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4
Q

Gout- molecular etiology

A
  • producing too much uric acid

- excreting too little uric acid

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5
Q

Gout- stages

A
  • hyperuricemia (asx)
  • acute flare (joint infl)
  • intercritical period (asx)
  • advanced/chronic gout (constant joint pain, infl, tophi)
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6
Q

medications for gout

A
  • Anti-infl drugs- termination of acute gout attack, prevent recurrences of acute gout
  • anti-hyperuricemic drugs
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7
Q

gout- drug classes

A
  • anti-infl
  • re-uptake inhibitors, enhanced excretion
  • syn inhibitors (inhibit XO)
  • uricosolytics
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8
Q

Anti-infl- drugs

A
  • NSAIDs
  • colchicine
  • corticoids
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9
Q

Re-uptake inhibitors, enhanced excretion- drugs

A
  • Probenecid

- Sulfinpyrazone

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10
Q

Syn inhibitors (XO inhibitor)- drugs

A
  • Allopurinol

- Febuxostat

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11
Q

Uricosolytics- drugs

A

-Rasburicase
-Pegloticase
(enhance urate metabolism)

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12
Q

NSAIDs

A
  • mainstay of tx for acute attacks of gout (no contraindication!!)
  • caution in pts w ulcers, HTN, coronary dz, fluid retention
  • inhibit COX
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13
Q

Colchicine- moa

A
  • binds to tubulin, depolymerizes MTs, and impairs migration of granulocytes- blunts infl
  • specific tx for acute gout!!!
  • not an analgesic
  • does not modify uric acid levels
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14
Q

Corticosteroids

A

(prednisone, methylprednisolone)

  • for gout attacks
  • long-term risks- osteoporosis, infection!!!!
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15
Q

Hyperuricemia- drugs

A
  • Xanthine oxidase inhibitors- inhibit biosyn
  • Uricosuric agents (URAT1 inhibitors)- enhance excretion
  • Recombinant urate oxidase enzyme- enhance metabolism
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16
Q

1st line urate lowering therapy (ULT)

A

XOIs

  • allopurinol
  • febuxostat
17
Q

what’s after 1st line??

A
  • oral ULT w oral uricosuric agent

- ULT w urate oxidase recombinant enzyme

18
Q

Allopurinol- moa

A
  • inhibit XO
  • Purine-> Hypoxanthine–XO-> Xanthine–XO-> Uric acid
  • active metabolite- oxypurinol
19
Q

Febuxostat- moa

A
  • inhibit XO

- can be used in pts with renal dz

20
Q

initial phase of ULT- paradox??

A
  • early inc in acute gout attacks- due to remodeling of articular urate crystal deposits
  • due to initiation of ULT!!
  • admin oral colchicine or NSAIDs in beginning of ULT to dec acute gout!!!
21
Q

Allopurinol and Febuxostat- complications

A

inhibit Xanthine drugs:

  • 6-Mercaptopurine
  • Azathioprine
  • Theophylline
  • reduced metabolism
22
Q

Allopurinol- compilication

A

hypersensitivity!! (black box warning)

-HLA-B*5801 (high allele freq in chinese, Thai descent- should be screened)

23
Q

Oral ULT w oral Uricosuric agent

A

(probenecid)

24
Q

Uricosuric agent- moa

A
  • promote renal clearance of uric acid
  • inhibit urate-anion exchanges in proximal tubule that mediates urate reabsorption
  • block URAT1 (urate transporter)!!!
25
Q

Uricosuric agent- avoid in who?

A

-risk/hx of nephrolithiasis or uric acid nephropathy

26
Q

Urate-lowering therapies- no benefit for?

A

-acute gout!!- shouldnt be initiated during an acute attack

27
Q

Aspirin- paradox?

A
  • do NOT use standard dose as an anti-infl agent for acute gout attacks- blocks tubular secretion!
  • high dose- reduces urate levels!
28
Q

thiazide and loop diuretics- do what?

A

-cause uric acid retention

29
Q

ULT w urate oxidase recombinant enzyme- moa

A

(pegloticase, rasburicase)

-augment metabolic degradation of uric acid into allantoin

30
Q

Pegloticase- indication

A

hyperuricemia assoc with malignancy (tumor lysis syndrome)!!!

MSK Pharm (10 decks)

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