4. Gout Flashcards
Define: Gout
Heterogenous disorder that results in deposition of uric acid salts and crystals in and found joints and crystallisation of uric acid in urinary joint
Describe the two different types of Gout
- Uric acid is the normal end product for the degradation of purine compounds
- Humans cannot break down uric acid into more soluble for Allantoin
- Hyperuricaemia - metabolic disorder
- Defined as 2SD above 7.0mg/dL - conc is limit of solubility for MSU in plasma - at high levels, MSU precipitates in tissues
What is the name of the enzyme that cannot break down uric acid?
Enzyme Uricase
When is peak incidence most probable with Gout?
5th decade - but it can occur in any age
Males
however incidence in women increase after menopause
What is gout?
excess production or reduced excretion of uric acid leading to deposition of uric acid crystals
What is the root cause of Gout?
What is it commonly associated with?
Hyperuricaemia
commonly associated with obesity, diabetes, hypertension, CHD, renal insufficiency and inc triglycerides
The formation of urate crystals leads too..
formation of tophaceous deposits
What is the most painful manifestation of Gout?
Gouty arthritis - caused berate crystals interact with neutrophils triggering an inflammatory response
What are the two types of hypereuricaemia?
Uric acid overproduction
- Genetic disorders: under regulation of purine nucleotide synthesis
- Hypoxanthine-guanine phosphoribzosyltransferase
Uric acid under-excretion
- Accounts for over 90% of hyperuricaemia
- Diminished tubular secretory rate, inc tubular reabsorption , diminished uric acid filtration
Name 5 of 6 drug groups that can cause gout
Why do they cause it?
- ACE inhibitors - Reduced rate renal clearance
- Cytotoxic chemo - Cisplatin - Rapid cell lysis - breakdown of cells causes more purines
- Ciclosporin - Dec grate clearance, defc GFR
- Diuretics - inc uric acid retention
- Ethanol - Inc uric acid production due to adenine nucleotide turnover
- Levodopa - Inhibition urate secretion
How is inflammation caused in joints?
Urate crystals are phagocytised by synovicytes
- Release PGs, lysosomal enzymes and IL-1
- These attract and activates polymorphonuclear leukocytes and mononuclear phagocytes
- PMN and MNPs migrate to joint space and amplify inflammation
- In the later phases of an attack, macrophages digest rate crystals and release more inflammatory mediators
4 stages of gout
- asymptomatic hyperuricaemia - leading to progressive urate crystal deposition
- acute gouty arthritis
- intercritical gout - the period between gouty attacks
- Chronic tophaceous gout
What can precipitate gouty attacks?
- Trauma
- Surgery
- Excessive alcohol consumption
- drugs
- purine rich food
How do we investigate gout?
- Serum Urea and Creatinine - renal impairment
- Joint fluid microscopy - long needle shaped crystals that are negatively birefringement (glow) in polarised light
Name some purine rich foods?
- All meats - gravy, anchovies, sardines, herring
- Mushrooms, lentil, kidney beans and asparagus
- Beer
What is acute gout?
- Associated with big toe
- Pain and inflammation b y uric acid crystal deposition
- More common in men, obesity, HPT
- Sudden symptoms - appear overnight
- Red and painful
How do we aim treat the different kinds of gout?
- Acute - Pain and inflammation
- Chronic - Attack prevention
- Lifestyle advice
What caution should we take with long term drugs
DO NOT give during acute attack
It exacerbates the pain and inflammation
How do we do lifestyle management?
Weight loss
Dietary modification
First line treatment for acute gout
- First line - NSAIDs
- Diclofenac - 100mg start, then 50mg tds for 2 days then 50mg bds for 8 days
- Indometacin - 75-100mg bds then reduce dose after 5 days
- Naproxen - 750mg start then 250mg ads
- Piroxicam 40mg daily then 10-20mg daily
- Etoricoxib - only COX2 - 120mg daily
Second Line treatment for acute gout
Dose?
Colchicine
- administer ASAP
- 1mg initially followed by by 0.5mg every 2-3 hours until pain, GI symptoms
- 6mg max dose
Corticosteroids - IA injections. Oral prednisolone 30mg/day for 7 days
Chronic treatment for gout - 1st line
Xanthine oxidase inhibitors
- Allopurinol and febuxostat
- 100mg daily and inc 3-4 weeks
- Maintenance dose 100-600mg daily
- Febuxostat is given 40-80mg daily
Chronic treatment of gout - 2nd
Uricosuric drugs
- Probenecid - 500mg-1g twice daily
- Sulphinpyrazone - - 100mg tds-qds
Not useful in patients over-producing uric acid or with poor renal functions
How do uricosuric drugs work?
- They act on URAT1 to prevent re-uptake or uric acid and thus increase its renal excretion
What is Lesinurad?
- Selective uric acid reabsorption inhibitor (SURI) that inhibits the URAT1 transporter
How does Lesinurad work?
- Inhibit URAT1, lesinurad increases uric acid excretion and thereby lowers serum uric acid (sUA)
- It also inhibits OAT4, a uric acid transporter involved in diuretic-induced hyperuricaemia
What do we monitor with Lesinurad?
Renal function
What drug can be given during chemo?
- Rasburicase
What is the enzyme responsible for converting uric acid to allantoin?
- Uricase
What are the common side effects of Rasburicase and Uricase?
- Fever
Why can we not use pegloticase?
- Side effects - anaphylactic reactions with the production of antibodies that neutralise uricase enzyme activity
- cost effectiveness
What is canakinumab? why don’t we use it?
anti IL-1 therapy
- far too expensive
