Gout and Hyperuricemia Flashcards
uric acid formation and disposition
- major product of purine metabolism
- biosyn of urate via XO
- kidney- filtered urate is reabsorbed via URAT1
Uric acid- description
- low water solubility
- forms sharp needle-like crystals- deposited in joints, kidneys, or soft tissues
Hyperuricemia (necessary but not sufficient to produce gout)- factors contributing to gout attacks in the 1st metatarsal-phalangeal joint
- lower T
- low pH
- joint dehydration
- altered matrix proteins, exposed cartilage fragments, and nucleating debris (joint trauma)
Gout- molecular etiology
- producing too much uric acid
- excreting too little uric acid
Gout- stages
- hyperuricemia (asx)
- acute flare (joint infl)
- intercritical period (asx)
- advanced/chronic gout (constant joint pain, infl, tophi)
medications for gout
- Anti-infl drugs- termination of acute gout attack, prevent recurrences of acute gout
- anti-hyperuricemic drugs
gout- drug classes
- anti-infl
- re-uptake inhibitors, enhanced excretion
- syn inhibitors (inhibit XO)
- uricosolytics
Anti-infl- drugs
- NSAIDs
- colchicine
- corticoids
Re-uptake inhibitors, enhanced excretion- drugs
- Probenecid
- Sulfinpyrazone
Syn inhibitors (XO inhibitor)- drugs
- Allopurinol
- Febuxostat
Uricosolytics- drugs
-Rasburicase
-Pegloticase
(enhance urate metabolism)
NSAIDs
- mainstay of tx for acute attacks of gout (no contraindication!!)
- caution in pts w ulcers, HTN, coronary dz, fluid retention
- inhibit COX
Colchicine- moa
- 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
Corticosteroids
(prednisone, methylprednisolone)
- for gout attacks
- long-term risks- osteoporosis, infection!!!!
Hyperuricemia- drugs
- Xanthine oxidase inhibitors- inhibit biosyn
- Uricosuric agents (URAT1 inhibitors)- enhance excretion
- Recombinant urate oxidase enzyme- enhance metabolism
1st line urate lowering therapy (ULT)
XOIs
- allopurinol
- febuxostat
what’s after 1st line??
- oral ULT w oral uricosuric agent
- ULT w urate oxidase recombinant enzyme
Allopurinol- moa
- inhibit XO
- Purine-> Hypoxanthine–XO-> Xanthine–XO-> Uric acid
- active metabolite- oxypurinol
Febuxostat- moa
- inhibit XO
- can be used in pts with renal dz
initial phase of ULT- paradox??
- 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!!!
Allopurinol and Febuxostat- complications
inhibit Xanthine drugs:
- 6-Mercaptopurine
- Azathioprine
- Theophylline
- reduced metabolism
Allopurinol- compilication
hypersensitivity!! (black box warning)
-HLA-B*5801 (high allele freq in chinese, Thai descent- should be screened)
Oral ULT w oral Uricosuric agent
(probenecid)
Uricosuric agent- moa
- promote renal clearance of uric acid
- inhibit urate-anion exchanges in proximal tubule that mediates urate reabsorption
- block URAT1 (urate transporter)!!!
Uricosuric agent- avoid in who?
-risk/hx of nephrolithiasis or uric acid nephropathy
Urate-lowering therapies- no benefit for?
-acute gout!!- shouldnt be initiated during an acute attack
Aspirin- paradox?
- do NOT use standard dose as an anti-infl agent for acute gout attacks- blocks tubular secretion!
- high dose- reduces urate levels!
thiazide and loop diuretics- do what?
-cause uric acid retention
ULT w urate oxidase recombinant enzyme- moa
(pegloticase, rasburicase)
-augment metabolic degradation of uric acid into allantoin
Pegloticase- indication
hyperuricemia assoc with malignancy (tumor lysis syndrome)!!!
