Gout Treatment

Question 1

Outline the phases of gout

Answer 1

Asymptomatic hyperuricaemia –> acute gout attack –> sporadic acute attacks —> recurrent flares w/ asymptomatic ‘intercritical period’ –> chronic gouty arthritis

Question 2

What are Tophi?

Answer 2

Macroscopic urate deposits = composed of monosodium urate crystals surrounded by macrophages and mast cells covered in connective tissue

Question 3

What are some complications of gout?

Answer 3

Gouty arthritis = disabling

Nephrolithiasis = formation of kidney stones

Chronic urate nephropathy

Question 4

What can cause gout? (Meds/food/cells)

Answer 4

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

Question 5

What are the treatment goals for gout?

Answer 5

Manage symptoms of an acute attack

Reduce freq of acute flares

Prevent progressive joint destruction and tophaceous deposition

Question 6

What are the main drugs used in gout?

Answer 6

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

Question 7

What are the first line therapies for an acute gout attack?

Answer 7

local corticosteroid = max two to affected site

NSAID orally = until sx improve

prednis(ol)one = until sx improve

colchicine

Question 8

How are corticosteroids useful in gout?

Answer 8

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

Question 9

How are NSAIDs useful in gout?

Answer 9

All NSAID except aspirin and salicylates = work for acute attack

Inhibit prostaglandin synthetase

Inhibit urate crystal phagocytosis

Question 10

Why is aspirin use not indicated for gout?

Answer 10

Causes renal retention of uric acid at low doses

Question 11

What is the mechanism of colchicine in gout?

Answer 11

Inhibit leukocyte and phagocytosis, formation of leukotriene B4

0.5mg once or twice a day

Question 12

When should urate lowering treatment be started?

Answer 12

Person >/=2 acute attacks within one year

Has evidence of bony changes or tophi consistent with gout

hyperuricaemia should not be treated

Question 13

How long do people remain on urate lowering therapy?

Answer 13

Lifelong, without breaks

W/drawal of therapy causes relapse in 1/2 of pts in 2 yrs

Question 14

What are the drugs used in urate lowering therapy?

Answer 14

Xanthine oxidase inhibitor = allopurinol, febuxostat

Question 15

What does allopurinol do?

Answer 15

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)

Question 16

What are some ADRs associated with allopurinol?

Answer 16

LFT abnormality

Skin Rash

Allopurinol hypersensitivity syndrome = steven johnsons, fever, organ damage

Question 17

What drugs interact with allopurinol?

Answer 17

Anything metabolised by xanthine oxidase = azathioprine, theophylline, 6-mercaptopurine

Will inc cyclosporine and warfarin

Thiazides influence renal clearance

Question 18

What is febuxostat? (what is? role?)

Answer 18

Xanthine oxidase inhibitor = structurally diff from allopurinol

used if allopurinol is not effective/sensitivities

Hepatic and renal clearance

Question 19

What are the risks/ADRs of febuxostat?

Answer 19

Inc CVD risk - not recommended in HF or IHD

Inc TSH

Question 20

What is probenecid? (what is? ADRs?)

Answer 20

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

Question 21

What commonly happens when ULT are started?

Answer 21

rapid dec in serum uric acid –> mobilisation of uric acid deposits and flares

Used NSAIDs = 3-6 months or colchicine

Question 22

How is a gout flare treated in someone stable on ULT?

Answer 22

Treat using acute treatment strategies and continue preventative medication

Question 23

Outline the therapies (in order) used in ULT flare prophylaxis

Answer 23

1) Colchicine - 1-2 daily

2) NSAID - lower end of dosing range

3) prednis(ol)one

Question 24

How long should ULT flare prophylaxis be used for?

Answer 24

6 months

OR

Until patient has no further attacks and target serum uric acid concentration achieved

Question 25

What are some high purine foods?

Answer 25

Offal, venison, turkey, bacon

Shellfish

small oily fish

yeast-rich food

Question 26

What are some low purine foods?

Answer 26

Soft drinks, coffee

Fruits

Bread, grains

eggs

dairy

sugar

veges

Question 27

What is uricase -pegloticase?

Answer 27

Pegylated porcine-like recombinant uricase

Used in severe tophaceous gout

Question 28

What is rasburicase used for?

Answer 28

treatment of tumour lysis syndrome

Question 29

What are some risks/ADRs of uricase - pegloticase?

Answer 29

Anaphylaxis

Antibody development

Initial gout flare in >80%, despite prophylaxis with NSAIDs or colchicine

Used in tumour lysis syndrome

Question 30

Name some moderate purine foods

Answer 30

Beef/beef stock

ham

chicken, duck

mushrooms, asparagus, spinach

kidney beans