Gout Treatment Flashcards
Outline the phases of gout
Asymptomatic hyperuricaemia –> acute gout attack –> sporadic acute attacks —> recurrent flares w/ asymptomatic ‘intercritical period’ –> chronic gouty arthritis
What are Tophi?
Macroscopic urate deposits = composed of monosodium urate crystals surrounded by macrophages and mast cells covered in connective tissue
What are some complications of gout?
Gouty arthritis = disabling
Nephrolithiasis = formation of kidney stones
Chronic urate nephropathy
What can cause gout? (Meds/food/cells)
Uric acid formed in the liver due to purine breakdown (food, beer, cell death, fructose sweetener) –> excreted by kidney (2/3) and gut (1/3)
thiazides, loop diuretics, ciclosporin = dec uric acid excretion from kidney
*we are unable to breakdown uric acid further
What are the treatment goals for gout?
Manage symptoms of an acute attack
Reduce freq of acute flares
Prevent progressive joint destruction and tophaceous deposition
What are the main drugs used in gout?
Allopurinol = inhibit uric acid formation
Colchicine = less/supress immune response to crystals
Probenecid = prevent reabsorption of uric acid in kidney
NSAIDs = acute attack pain/inflammation relief
What are the first line therapies for an acute gout attack?
local corticosteroid = max two to affected site
NSAID orally = until sx improve
prednis(ol)one = until sx improve
colchicine
How are corticosteroids useful in gout?
Suppress aspects of inflammatory process
Reduce neutrophil migration
Inhibit macrophage phagocytosis
Reduce macrophage production of IL-1, TNF_a, MMPs, tPA
Reduce expression of CoX-2
How are NSAIDs useful in gout?
All NSAID except aspirin and salicylates = work for acute attack
Inhibit prostaglandin synthetase
Inhibit urate crystal phagocytosis
Why is aspirin use not indicated for gout?
Causes renal retention of uric acid at low doses
What is the mechanism of colchicine in gout?
Inhibit leukocyte and phagocytosis, formation of leukotriene B4
0.5mg once or twice a day
When should urate lowering treatment be started?
Person >/=2 acute attacks within one year
Has evidence of bony changes or tophi consistent with gout
hyperuricaemia should not be treated
How long do people remain on urate lowering therapy?
Lifelong, without breaks
W/drawal of therapy causes relapse in 1/2 of pts in 2 yrs
What are the drugs used in urate lowering therapy?
Xanthine oxidase inhibitor = allopurinol, febuxostat
What does allopurinol do?
Reduces production of uric acid from precursors
Effective in both ‘over-producers’ and ‘under-excretors’
Eliminated renally (adjust dose and caution in acute kidney injury)
What are some ADRs associated with allopurinol?
LFT abnormality
Skin Rash
Allopurinol hypersensitivity syndrome = steven johnsons, fever, organ damage
What drugs interact with allopurinol?
Anything metabolised by xanthine oxidase = azathioprine, theophylline, 6-mercaptopurine
Will inc cyclosporine and warfarin
Thiazides influence renal clearance
What is febuxostat? (what is? role?)
Xanthine oxidase inhibitor = structurally diff from allopurinol
used if allopurinol is not effective/sensitivities
Hepatic and renal clearance
What are the risks/ADRs of febuxostat?
Inc CVD risk - not recommended in HF or IHD
Inc TSH
What is probenecid? (what is? ADRs?)
uricosuric agent, ineffective in renal impairment
Long term use = GI complaints and rash
Risk/ADRs = rash, uric acid kidney stones
Used when target serum uric acid cannot be reached with allopurinol
What commonly happens when ULT are started?
rapid dec in serum uric acid –> mobilisation of uric acid deposits and flares
Used NSAIDs = 3-6 months or colchicine
How is a gout flare treated in someone stable on ULT?
Treat using acute treatment strategies and continue preventative medication
Outline the therapies (in order) used in ULT flare prophylaxis
1) Colchicine - 1-2 daily
2) NSAID - lower end of dosing range
3) prednis(ol)one
How long should ULT flare prophylaxis be used for?
6 months
OR
Until patient has no further attacks and target serum uric acid concentration achieved
