Module 1.3.2 (Therapeutic Management of Gout) Flashcards
What are the risk factors of gout?
- Age
- Renal disease —> body cannot get rid of uric acid
- Obesity
- Male
- Metabolic disorders including hypertension and insulin resistance
- Medication e.g. thiazide diuretics, cyclosporine, nicotinic acid, levodopa, low dose aspirin
What are the signs and symptoms of GOUT?
- Sudden onset of monoarticular arthritis (common in first metatarsophalangeal (MTP) joint)
> other joint(s) can be affected
- Rapid onset of pain or redness in the affected joint(s)
What are the laboratory findings in GOUT?
- Presence of characteristic urate crystals in the joint fluid by polarized light microscopy
- Patient has hyperuricemia
What are the THREE types of Gout Attack? Briefly describe what each type constitutes and the symptoms associated with it.
- Acute gouty arthritis
- first attack monoarticular (80% in big toe); 10% polyarticular (ankles, DIP joint, elbows, knees)
- severe pain in affected joint(s)
- red, hot, swollen joints and exquisitely tender
- resolve with drug treatment
- remission periods vary
- risk of permanent joint deformity if not treated
- Chronic tophaceous gout
- Tophi (uric acid crystal aggregates) deposits in joints
- Ongoing low-grade inflammation
- Joint deformity
- Gouty nephropathy
- deposition of uric acid crystals in renal tubules
- mononuclear cell infiltration, fibrosis, proteinuria +/or renal impairment
What is the treatment goal for;
A) Acute attack?
B) Chronic hyperuricaemia
A)
- Reduce inflammation , relieve pain and shorten duration of attack
- Commence tx within 24 hours of sx onset
B)
- Reduce serum urate levels to prevent acute attacks and joint destruction, disability, nephrolithiasis and renal disease
How to minimize exacerbating factors when using medications to treat comorbidities?
Stop using;
- Low dose aspirin
- Thiazide diuretics
What are some non-pharmacological management options for gout?
- Decrease weight
- Reduce alcohol, esp.beer –> contains purine which is a precursor to uric acid
- Diet –> significant source of urate precursors
> Decrease animal offal and seafood (shellfish, anchovies, sardines)- inconclusive evidence
> Decrease beverages sweetened with fructose i.e. soft drinks and fruit juices
For the treatment of acute gout, when to use;
A) NSAIDs?
B) Corticosteroids? What to ensure prior to starting corticosteroids?
C) Colchicine?
- NSAIDs –> DRUG OF CHOICE if not contraindicated
- Indomethacin, naproxen (least cardiovascular risk out of all NSAIDs)
- Usually effective within 3 to 5 days
- Corticosteroids
- If NSAIDS or colchicine contra-indicated e.g. in renal impairment, heart failure or in anticoagulated patients
- Make sure there is no infection in affected joints
- Oral (prednisolone)
- Intra-articular steroid injection for those with a single joint involvement
- Colchicine
- If NSAIDS and corticosteroids contra-indicated
- Anti-inflammatory effect
- Most effective if initiated early (70-90% response rate)
- Interim pain relief with paracetamol
- Caution in patients with hepatic or renal impairment
- 1mg initially, then 0.5mg 1 hour later (max of 1.5mg per course)
> do not repeat treatment within 3 days (if CrCL <30mL/min, this changes to 2 weeks between repeating treatment)
For colchicine;
A) What are some adverse effects?
B) What is there risk of in renal disease?
C) Which CYP… inhibitor to be cautious with as it increases the risk of colchicine toxicity?
D) What to avoid combinations with?
A)
- GI, blood dyscrasias, peripheral neuropathy
B)
- Risk of myelosuppression in renal disease
> Avoid or extend the interval between colchicine treatment courses to 2 weeks
C)
- CYP3A4 inhibitor –> protease inhibitors, erythromycin, verapamil, diltiazem, grapefruit juice
D)
- Avoid combination with statins – risk of rhabdomyolysis
Give FOUR reasons to start prophylactic tx (urate lowering therapy) in gout?
If the patient has at least ONE of the following:
- tophi (uric acid crystal aggregates)
- two or more acute gout attacks a year
- chronic kidney disease (stage 2 or worse)
- urolithiasis (uric acid stone in kidney)
What are some examples of long term urate-lowering treatment in gout? How to titrate the dose?
- Allopurinol and febuxostat (uricostatic) –> reduce uric acid production –> xanthine oxidase inhibitor
- Probenecid (urocosuric) –> increase urinary acid excretion
Start low, increase the dose slowly, continue longterm – do not stop during an acute attack if the patient is already on it
For Allopurinol (long term ULT);
A) Is it 1st line?
B) How to start the dose and adjust from there?
C) How does eGFR < 30mL/min change the answer in part B?
D) When to stop treatment in patients who have tophi and normal patients?
E) What are some precautions?
F) Can it be started during an acute attack?
G) What are some adverse effects?
A)
- Yes
B)
- Start at 100mg daily for one month and increase the daily dose by 50mg every 2-4 weeks until target serum uric acid conc is reached
- Dose range: 300 to 900mg daily
C)
- In renal impairment (eGFR < 30mL/min) start the patient on a very low dose (1.5 mg per mL eGFR) with very gradual up-titrating (25–50 mg per month)
D)
Treat to target
- A target serum uric acid of <0.30 mmol/L when tophi are present
- < 0.36 mmol/L in all other patients
E)
- Asian descent (develop hypersensitivity) and previous hypersensitivity reaction to allopurinol
> hypersensitivity = fever, the onset of acute dermatitis, renal and hepatic dysfunction
F)
- Yes but only if COMBINED with acute gout treatment
G)
- Acute gout attack, hypersensitivity reactions, hepatotoxicity, altered taste, drowsiness, nausea and diarrhoea
For Febuxostat (long term ULT);
A) Who is it used for?
B) Can it be started during an acute gout attack?
C) What is the dose equivalence with allopurinol?
D) How to treat to target?
E) Precautions?
F) A/Es?
A)
- Reserved for patients who cannot tolerate allopurinol
B)
- Not initiated during an acute gout attack
C)
- 40 mg per day is clinically equivalent to allopurinol 300 mg in efficacy
D)
- Start at 40 mg once daily
- Assess serum urate at 2-4 weeks; if > 0.36 mmol/L increase dose to 80 mg once daily
E)
- Ischaemic heart disease, heart failure, hypersensitivity to allopurinol or febuxostat, CrCl <30 mL/min, hepatic impairment
F)
- Acute gout attack, hypersensitivity reactions, hepatotoxicity
For Probenecid (long term ULT);
A) MOA
B) Can be started during acute attack?
C) CI?
D) Ensure patient is …. to prevent formation of renal stones
E) Dose?
F) A/E
G) Drug interactions?
A)
- Enhance renal clearance of uric acid
- Reduced efficacy when renal clearance < 50mL/min
B)
- Not initiated during an acute gout attack
C)
- C/I in patients with kidney stones
D)
- Well hydrated
E)
- Treat to target
- Start at 250 mg bd for 1 week
- Maintenance dose: 500 mg bd to 2 g ddd
F)
- Rash, nausea, vomiting, uric acid kidney stone (prevent by ensuring adequate fluid intake)
G)
- Aspirin
> Does not apply to low dose aspirin for antiplatelet treatment
There is an increased risk of acute gout attack due to fluctuations in serum urate levels when starting treatment with URT and when changing the dose. What to use for prophylaxis (include doses)?
- low-dose colchicine (0.5mg od-bd)
- NSAIDs (indomethacin 25mg bd or naproxen 250 mg bd) for at least 6 months)
Provide a summary for GOUT
- Initiate pharmacologic therapy asap at the onset of acute gout attack while continuing urate-lower therapy without interruption (if already on ULT).
- Otherwise, ULT should NEVER be commenced during an acute attack with the exception of allopurinol
- NSAIDs is the first-line treatment for acute gout. Corticosteroids or colchicine can be an option if NSAID is contraindicated
- Prophylactic treatment with ULT for gout is only indicated in certain patients
- Allopurinol as first line treatment ULT for prevention of future episode of gout– start low go slow
- Low dose colchicine or NSAID is required for at least 6 months to prevent an acute flare when introducing prophylactic tx with ULT in gout
- Lifestyle modification (including dietary intake) is important to prevent recurrent gout
