Gout Flashcards
Who is susceptible for gout?
Men aged 30-60, genetic link is possible
What happens for a patient to get gout?
1) Hypoxanthine
2) Xanthine
3) Uric acid
*Each step is facilitated by Xanthine Oxidase
How are uric acid levels during gout?
Formation and deposition of monosodium urate crystal are more likely to occur when levels are persistently above 380 micromol/ml
How are crystals formed from gout?
pH of 7.4 uric acid is ionised making monosodium urate, if supersaturation occurs crystals are formed
When do symptoms of gout occur?
When the crystals shed into the bursa this causes an inflammatory reaction, can be triggered by trauma, dehydration, weight loss, illness or surgery.
How is an inflammatory response initiated, amplified and sustained in gout?
-Humoural and cellular inflammatory mediators and the complement system causes
-Cascade of TNF/cytokines
-Inflammatory cell accumulation
What early cells respond in gout?
Monocytes, mast cells
What late cells respond in gout?
Neutrophils
What is stage 1 of gout?
Asymptomatic hyperuricaemia
What is stage 2 of gout?
Acute gouty arthritis
-Skin sheds after 7 days untreated
-Severe, red, hot, swollen, painful
-Starts abruptly
-Synovitis
-WBC increased
-Confusion
What is stage 3 of gout?
Interval / Inter-critical gout
*can be months/years between attacks
What is stage 4 of gout?
Chronic tophaceous gout
-White deposits of monosodium urate, nodule formation which effects the joints
-subcutaneous and periarticular areas (ear lobes, achilles tendon,fingers)
What is stage 5 of gout?
Gouty nephropathy
-Crystals deposited around renal tubules - inflammatory response
-Proteinuria - renal impairment, kidney damage, kidney stones,
-Protein in urine +++
Are uric acid levels always high in a gout attack?
No
What are 10% of gout cases caused by?
Overproduction
What are 90% of cases of gout caused by?
Under excretion
-Causes large urate loads to be filtered through the glomerulus , this increases urate reabsorption in proximal tubules meaning insoluble urate isn’t dumped into the urinary tract.
-This decreases tubular secretion and reduced urate secretion
What is primary gout?
Rare and inborn errors of metabolism or renal excretion
What is secondary gout?
Caused by drugs or consequence of another disorder.
Can overconsumption of high purine foods cause gout?
YES
Can renal failure cause gout?
Yes, as uric acid isn’t being expelled
Can drinking alcohol cause gout?
Yes, as they contain high levels of purines, = under excretion, breaks the purine and uric acid is formed
What drugs can cause gout?
Diuretics, Aspirin, Ciclosporin, Omeprazole, Niacin, Levodopa
What should be done in an acute attack of gout?
Rest
Full dose of NSAID
What NSAID should be avoided in gout?
Aspirin
What is first line for acute gout?
NSAID + PPI
What is second line for gout?
Colchicine
0.5mg 2-4 times a day until relief
If a patient has colchicine how many days do they have to wait until they have a repeat course?
No repeat course within 3 days!
If a patient can’t have Colchicine, what should be offered?
Corticosteroids - prednisolone 30-35mg OD for 5 days
If pain is persistent in gout what injection can be given?
Triamcinolone
What is the triple therapy for gout?
NSAID + Colchicine + PPI
If a patient on Colchicine has GI disturbances what must happen?
It must be stopped, could be a sign of toxicity!
What is given for prophylaxis of gout?
1st line Allopurinol 00mg OD then titrate to 300mg-600mg OD
If intolerant swap to Febuxostat 80mg OD and increase to 120mg if uric levels above 357mmol/l after 2-4 weeks!
What is second line prophylaxis for gout?
Uricosuric agents ‘ones’
-If renal impairment avoid
If pt has severe gout what can be offered?
Canakinumab
What is the MOA of Allopurinol?
Interferes with synthesis of uric acid, Xanthine Oxidase Inhibitor!
What can there be a build up of when someone is on allopurinol?
Hypoxanthine and Xanthine - this is harmless and easily excreted!
What is allopurinol metabolised to?
Oxypurinol
What drug is better than Allopurinol?
Febuxostat
What is the MOA of Febuxostat?
Binds to channel at active site of Xanthine Oxidase and blocks entry, this is very effective as it binds to oxidised reduced from
What does taking Allopurinol and Azathioprine together do?
FATAL BONE MARROW SUPPRESSION!!!!!
Why?
-Azathioprine metabolised to mercaptopurine
-Mercaptopurine is metabolised by Xanthine oxidase
-Allopurinol causes accumulation
