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EXAM 1 > GOUT > Flashcards

GOUT Flashcards

1
Q

What is Gout?

A

Gout is a type of arthritis that causes sudden swelling and severe pain in the joints.

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2
Q

How does Gout come about?

A

Hyperuricaemia ( too much Uric acid that stays in the body. Hyperuricaemia causes uric acid to clump together in sharp crystals that settle in your joints = GOUT.

Can also build up in your kidneys and form kidney stones.

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3
Q

What is the name of the deposits that from the sharp crystals?

A

Deposition of monosodium urate monohydrate crystals in joints & soft tissues

Caused by increased production or decreased excretion or both

➔ acute inflammation & eventually tissue damage

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4
Q

What is the Epidemiology of Gout?

A

Prevalence (UK 2012) of gout = 2.49%

Incidence (UK) of gout = 1.77/1000/yr.

More common in men (30-60years) and in older people (rare in those under 20 years)
– Ratio – 4.3 : 1 (M:F)

More likely if FHx - genetic link

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5
Q

How is Uric acid synthesized?

A

Uric acid is end product of purine (adenine &
guanine) metabolism

Hypoxanthine - Xanthine
( xanthine oxidase)

Xanthine - Uric acid
(xanthine oxidase)

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6
Q

How is Uric acid Excreted?

A

Completely filtered by glomerulus

90-100% reabsorbed in proximal tubule
(URAT-1 specific anion transporter)

50% actively secreted in distal tubule
40-45% post secretary reabsorption
~ 5-10% of original glomerular load is
excreted

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7
Q

How much of the urate is excreted in the Urine?

A

2/3 of urate excreted in urine

1/3 of urate excreted in gastrointestinal tract

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8
Q

What is the Aetiology of GOUT?

A

Gout is caused by:

Increased rate of synthesis of Purine Precursors of Uric acid (10%)

Decreased Elimination of Uric acid by the Kidneys (90%)

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9
Q

What are the Classifications of Gout?

A

Primary:
– Due to rare inborn errors of metabolism or renal
excretion (not covered here)

Secondary:
– Occur due to drugs or consequence of other
disorder

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10
Q

How does Over- Consumption contribute to GOUT?

A

Over consumption of foods high in purines:

– Offal (liver, kidney, heart, sweetbreads), game,
oily fish (anchovies, herring, mackerel, sardines,
sprats, trout), seafood, yeast or meat extracts

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11
Q

How does Over- Production contribute to GOUT?

A

Only about 10% of cases

Excessive cell turnover (E.g: neoplastic
disease, psoriasis, haemolytic anaemias)

Cell lysis caused by cancer chemotherapy &
radiotherapy

Excessive synthesis of uric acid due to rare
enzyme mutation defects.

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12
Q

How does Under excretion contribute to GOUT?

A

Occurs in remaining 90% of cases

Hyperuricaemia ➔ large urate loads filtered
through glomerulus ➔ Increased urate reabsorption to avoid dumping of insoluble urate into urinary tract

Also decrease tubular secretion

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13
Q

What drug classes contribute to GOUT?

A

Renal failure

Alcohol (beer, red wine)

Drugs:
– Diuretics - Especially thiazides, furosemide
– aspirin, ciclosporin,, omeprazole, ethambutol,
pyrazinamide, niacin, didanosine, levodopa,
cytotoxics

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14
Q

What physical stress activities and other independent risk factors contribute to GOUT?

A

Physical Stress
– Tight shoes, hill walking, hiking, history of joint
trauma

Other independent risk factors: hypertension,
obesity hypertriglyceridemia

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15
Q

What is the pathophysiology of GOUT?

A

Hyperuricaemia is the most important risk factor
for gout

Uric acid levels:
– Formation and deposition of monosodium urate crystals is more likely to occur when levels are persistently > 380 micromol/mL (solubility limit)

HIGHER plasma urate level ➔ Increased incidence of gout

PROLONGED DURATION of increased urate levels ➔
increase likelihood of developing gout.

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16
Q

What acid is Uric acid and what happens to it at physiological PH?

A

Uric acid = weak acid (pKa 5.8)

At physiological pH ➔ ionised ➔ monosodium
urate (MSU)

If supersaturation occurs ➔ crystal formation

Solubility is influenced by:
– Temperature, pH, cation concentration, articular
dehydration and presence of nucleating agents (nonaggregate proteoglycans, insoluble collagens and chondroitin)

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17
Q

What happens to Crystal deposits for them to cause symptoms?

A

Crystal deposition may continue for many
months or years without causing symptoms

Only cause symptoms when shed into bursa (small sacs of synovial fluid surrounding
joint) ➔ inflammatory reaction

Shedding can be triggered by e.g: – Trauma, dehydration, rapid weight loss, illness &
surgery

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18
Q

Urate crystals are directly able to initiate, amplify
and sustain inflammatory responses, through?

A

Humoral and cellular inflammatory mediators

Complement system

Overall this causes:
a proinflammatory cascade of cytokines, chemotactic factors, TNF

Inflammatory cell accumulation (monocytes and mast cells in
the early phase and neutrophils in the later phase)

IL-1beta has been shown to be critically related to
the inflammatory response in gout

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19
Q

What are the 5 stages of the clinical presentations of GOUT?

A

– Asymptomatic hyperuricaemia (long period before gout manifests)

– Acute gouty arthritis

– Interval gout/Intercritical gout

– Chronic tophaceous gout

– Gouty nephropathy

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20
Q

What is Acute Gouty Arthritis?

A

90% acute attacks monoarticular

80% first metatarsophalangeal joint of great toe (podagra)

Severe pain with hot, red, swollen and extremely painful joints

Begin abruptly – max intensity 8-12hrs, Weight bearing impossible, Erythema, Synovitis, Leucocytosis, Confusion in elderly

21
Q

What happens if Acute Gouty Arthritis is left untreated?

A

Left untreated last around 7 days ➔ desquamation of overlying skin

Attack at anytime but can be caused by trigger factors (E.g: food, alcohol, dehydration, starting diuretic)

22
Q

Facts about Intercritical Gout?

A

Time between acute attacks of gout

Variable intervals of months to years when there are no symptoms

23
Q

Facts about Chronic Tophaceous Gout?

A

Presence of tophi:

– White deposits of monosodium urate
– Nodule formation affecting joints
– Subcutaneous and periarticular areas
– Ear lobes, Achilles tendon, fingers

24
Q

Facts about Gouty nephropathy/ Hyperuricaemia
induced renal disease?

A

Crystals of urate deposited around renal tubules
➔ inflammatory response (interstitial nephritis)

Proteinuria & renal impairment

Renal stone formation

25
Q

What is the Diagnosis of GOUT?

A

Has to be based on clinical history and examination.

Uric acid levels can be useful but are not always raised when someone has an acute attack.

Joint fluid microscopy – presence of crystals and
absence of infection (to rule out septic arthritis)
– Not always done as it risks causing infection

Joint X-ray

Standard bloods – RF, lipids, glucose

26
Q

What are the aims of treatment for Gout?

A

Relieve pain/inflammation of acute attack

Terminate attack

Prevent further attacks

Prevent long term joint and organ damage

Avoid precipitating factors

27
Q

What is the treatment for Acute Gout?

A

Rest

Prompt treatment with full dose NSAIDs

Avoid ASPIRIN:
– Competes with uric acid for excretion and can
worsen attack

28
Q

What is the FIRST line treatment for GOUT and what does it do?

A

NSAIDS: Relieve pain & inflammation

Can abort acute attack if commenced early enough (patients should carry supplies)

Most important factor is how soon started rather than choice of NSAIDs

Full therapeutic high dose for 24-48hrs then
lower doses for 7-10 days until completely resolved

Consider gastroprotection e.g. lansoprazole

29
Q

What is the SECOND line treatment for GOUT and what does it do?

A

COLCHICINE: Used second line when NSAIDs contraindicated or ineffective

– Eg: CVD (HT, heart failure, diuretics), Renal disease
Gastrointestinal toxicity

Slower onset + high level of toxicity

Inhibits neutrophil migration into joint

30
Q

What is the Dose for Colchicine and why should you administer it ASAP?

A

Dose: 0.5mg 2-4 times a day until relief of joint pain or development of GI side effects or total 6mg taken – do not repeat course within 3 days

Lower dose of 0.5mg every 8 hrs in elderly and renal impairment

ADMINISTER DOSE ASAP as it is less effective over time

31
Q

What are the Colchicine times for response, pain relief and resolution?

A

Response after 6 hrs, pain relief after 12 hrs
and resolution after 48-72 hrs

32
Q

What are the Side-effects of Colchicine?

A

– Nausea & vomiting

– Abdominal pain

– Diarrhoea (stop therapy immediately)

– Rashes, peripheral neuropathy, blood dyscrasias

33
Q

What is the dose of Corticosteroids FOR Gout?

A

Oral: e.g. Prednisolone 30-35mg daily (or equivalent)

Pred 35mg daily for 5 days as effective as naproxen
500mg BD for 5 days for flare treatment.
Pred 30mg daily for 5 days has analgesic effectiveness
equivalent to indomethacin

Articular: e.g. Triamcinolone = good safety profile
– Consider particularly in monoarthritis of easily
accessible joint

34
Q

What is Combination therapy for Gout?

A

NSAID with colchicine or corticosteroid

35
Q

You traditionally do not start prophylaxis during an acute attack?

A

TRUE

36
Q

You should treat Hyperuricaemia lasting several years immediately?

A

FALSE

Changes (DECREASE ) serum uric acid levels ➔ mobilisation of uric acid stores ➔ may prolong attack or precipitate another

37
Q

What drug did small trials indicate that its initiation did not prolong duration or worsen severity of GOUT attack?

A

Allopurinol

38
Q

What does Urate lowering Therapy do?

A

– Reduces frequency of flare

– Once crystals dissolved avoids recurrence

– Reduces size and number of tophi

– Facilitates tophi disappearance: IMPROVED QoL

39
Q

All ULT should be started at a low dose and titrated upwards?

A

TRUE

– Monitor and titrate to serum uric acid (sUA) target

40
Q

What is the Prophylaxis (ULT) for GOUT?

A

first 6-months of
ULT or during a dose titration

Colchicine – first line
– 0.5-1mg daily
– Reduce in renal impairment

Where contraindicated or not tolerated
– Low dose NSAID or coxib should be considered
(consider cautions etc.)

With gastroprotection

41
Q

What is the first line drug choice for prophylaxis of Gout?

A

ALLOPURINOL

Controls symptoms

Some improvement in tophi (usually after about 6 months treatment)

Xanthine oxidase inhibitor

Pro-drug ➔ undergoes hepatic metabolism
to active metabolite, oxipurinol

42
Q

What is the Dosing of Allopurinol?

A

Start 100mg daily
– Increase every 3-4 weeks according to response to achieve decreased serum urate levels (target sUA <300µmol/L)

– Usual maintenance 300mg daily (100-600mg)

– Accumulate in renal impairment (Dose 50-100mg
daily)

43
Q

What are the side effects of Allopurinol?

A

– Rashes

– Hypersensitivity reactions

– Gastrointestinal disturbances

44
Q

When should you start taking Allopurinol?

A

Start 1-2 weeks after acute attack subsided

If patient already on Allopurinol at onset of
acute attack ➔ continue & treat acute attack

Allopurinol can be used for prevention of diuretic induced hyperuricaemia if no alternative

45
Q

What is the ALTERNATIVE/ C.I to Allopurinol?

A

Febuxostat: Non-purine selective inhibitor of xanthine oxidase

Dose: 80mg od (↑ to 120mg if uric acid levels >357μmol/l after 2-4 weeks)

Continue if acute attack occurs during prophylaxis

Side-effects: G.I., headache, ↑LFTs, oedema, rash

Rare but serious hypersensitivity reactions

46
Q

What is the second line ALTERNATIVE to Allopurinol/ Febuxostat?

A

URICOSURIC AGENTS (Eg: Sulfinpyrazone)

Increase uric acid excretion by direct action on renal
tubule

Avoid in urate nephropathy

Ineffective in poor renal function (CrCl <20-30
ml/min)

Need to maintain high fluid intake to Reduce risk of stone formation

47
Q

What drug is Canakinumab?

A

Recombinant monoclonal antibody ( S/C injection)

Target interleukin-1ᵝ associated with inflammatory response induced by urate crystals

Severe, refractory tophaceous gout (NICE,2013)

C/I in current infection – due to risk of sepsis

48
Q

What others could reduce Uric acid but they are not licensed by NICE?

A

Pegloticase (Pegylated uricase, catalysing the oxidation of uric acid into
allantoin (more soluble end product)

Anakinra (IL-1 receptor antagonist)…… Licensed RA

Rilonacept (IL-1alpha/beta antagonist and IL-1R antagonist)

49
Q

What IMPORTANT INTERACTION does Allopurinol have with another drug?

A

ALLOPURINOL+AZATHIOPRINE

Azathioprine metabolised to mercaptopurine

Mercaptopurine metabolised by Xanthine oxidase

Allopurinol causes accumulation ➔ Potentially fatal bone marrow suppression

EXAM 1 (14 decks)

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