CPT2: GOUT Flashcards
What is GOUT?
Gout is a disorder of purine metabolism characterized by a raised uric acid level in the blood (hyperuricaemia) and the deposition of urate crystals in joints and other tissues, such as soft connective tissues or the urinary tract.
The urate crystals formed in the joins can cause severe episodes of pain, tenderness, redness, warmth and swelling
What stages of GOUT is there
What causes hyperuricameia?
Three distinct phases:
- Asymptomatic hyperuricaemia
- Prolong period of rasied uric acid in blood but no symptoms
- Acute attacks followed by intervals of no symptoms
- Chronic tophaceous gout
Hyperuricaemia caused by undersecretion (in 90%) or over production (10%)
Prevelance?
- Most common in older people and men
Risk factors?
- Other risk factors:
- Diet
- Alcohol
- Menopausal women
- Renal disease
- Obesity
- Metabolic syndrome
- Dyslipidaemia
- Use of certain medications (e.g. low-dose aspirin, ciclosporin, diuretics, ethambutol, nicotinic acid, pyrazinamide, tacrolimus)
- Trauma
- Genetics
Why is diet a risk factor?
Uric acid is made in the body from a breakdown of purines that come from the diet, therefore a diet containing foods high in purine may lead to hyperuricaemia.
Foods high in purine:
- Offal – liver, heart, kidneys and sweetbreads
- Game – pheasant, rabbit, venison
- Oily fish – anchovies, herring, mackerel, shellfish, fish roe, caviar
- Meat and yest extracts – Marmite, Bovril, beer
Why is alcohol a risk factor?
- Many beers contain large quantities of purines from the fermenting process, and alcohol stimulates the production of uric acid by the liver.
- More importantly, alcohol is converted in the body to lactic acid which interferes with the removal of uric acid from the body by the kidneys.
- Government guidelines for alcohol consumption – both men and women are advised not to regularly drink more than 14 units a week.
What are causes of overproduction or uric acid and undersecretion?
Underexcretion of uric acid:
- Renal failure and drugs
- Alcoholism
- Primary idiopathic gout
- Rarely, familial hyperuricaemia nephropathy
Overproduction of uric acid:
- Excessive turnover of nucleoproteins (neoplastic disease), polycythaemia, chronic myeloid leukaemia
- Excessive dietary intake of purines
- Acute tumour lysis
- Chemotherpay causes cells to be broken down quickly and contents released into the circulation
Symptoms of GOUT
- Tends to attack joints which are cold so crystals can precipitate.
- Normally mono-articular - affects only one joint
- Severe pain in a joint – most commonly the metatarsophalangeal joint of big toe
- Red, hot to touch, painful and swollen.
- In chronic gout (develop around 10 years after onset) Tophi can form– these are large urate crystal filled lumpy nodules which occur under the skin most commonly form in the fingers, toes and helix of the ear. Normally appear white under skin and not normally painful
What does the diagnosis involve?
Upper limits?
- The ‘gold standard’ is demonstration by microscopy of urate crystals in synovial fluid or tophi, however this is often not practical.
- Based on clinical history and examination.
- Clinical history:
- Previous attacks
- Age of onset
- Under 30 probs more complex disease
- Possible risk factors
- Associated co-morbidity
- joints affected, how quick onset of symptoms (typically max after 24hr)
- Clinical history:
- •Serum uric acid is usually measured 4-6 weeks after an acute attack as urate levels can often fall during an acute attack
- Upper limits:
- 420micromol/L for males
- 360micromol/L for females
- Hyperuricaemia may be present without gout and vice versa.
What is the aims of treatment for prophylaxis of acute gout and treament of acute gout?
Differs depending on if treating acute or chronic gout:
- Prophylaxis of gout – reduce serum urate, prevent acute attacks and long-term joint damage and renal impairment
- Acute gout – reduce pain, inflammation and reoccurrence
Drugs for prophylaxis dont work for an attack but if taking them should continue during the attack
- Eliminate/ reduce risk factors
- Patients should be educated on risk factord e.g. alcohol and diet
- Also review medicine
During an acute attack what should a patient do?
Self-care:
- Rest and elevate the limb. (reduce swelling)
- Avoid trauma to the affected joint.
- Keep the joint exposed and in a cool environment.
- Consider the use of an ice-pack.
What is the uric acid renal pathway?
After glomerular filtration, uric acid is almost completely resorbed in the proximal tubule.
At the same time, there is secretion in the opposing direction in the proximal tubule.
Active process and is shared by other weak acids (e.g. low dose aspirin) and therefore these can interfere with uric acid excretion.
- Uric acid excretion is affected by:
- Tubular absorption – inhibited by high dose aspirin, uricosurics
- Tubular secretion – inhibited by low dose aspirin, thiazide diuretics
Competition for active transport mechanisms causes a fluctuation in plasma uric acid levels.
What is first line treatment in acute gout attacks?
First-line agents:
- NSAIDs – start at maximum dose as early as possible and continue until 1-2 days after attack has resolved (see OA lecture for prescribing advice).
- Aspirin is not indicated in gout as analgesic doses interfere with uric acid excretion.
- Colchicine - if NSAIDs not suitabl for patient
- Stop taking when symptoms stop or after a total of 6mg has been taken
Colchicine
MOA
Dose
Contraindications
Cautions
- Mode of action: not clearly understood – considered to act against the inflammatory response to urate crystals, by possibly inhibiting the migration of granulocytes into the inflamed area.
- Dose: 500 micrograms 2-4 times a day (reduce dose in renal impairment, contraindicated if eGFR <10mL/min/1.72m2).
- Contraindications: blood disorders, significant renal impairment, pregnancy, breastfeeding.
- Cautions: cardiac disease, elderly, GI disease.
Side effects
Drug interactions
Interactions:
- Possible risk of colchicine toxicity when concomitantly used with amiodarone, azithromycin, clarithromycin, diltiazem, erythromycin, grapefruit juice, verapamil.
- Possible risk of myopathy when concomitantly used with digoxin, fibrates, statins.
- Anti HIV med: itraconazole, ketocomozole
- Ciclosporin - risk of nephrotoxicty and myotocisty
- Side-effects: abdominal pain, nausea, vomiting, diarrhoea.
- First symptoms of toxiicty therefore stop or reduce dose
