4. Gout MT1 Flashcards
this is an inflammatory disease associated with the deposition of monosodium urate crystals (MSU) in joints and soft tissues due to chronic hyperuricemia
gout
this is when the serum is saturated with monosodium urate. concentrations are above/around 416 micromols/L for men and 357 micromols/L for women
hyperuricemia
true/false: sustained elevation of serum urate is essential for the development of gout, but hyperuricemia does not always lead to gout
true
what are some risk factors for developing gout?
- male gender
- increased age
- obesity, sedentary lifestyle
- consumption of alcohol, surgery beverages, and red meat (food high in purines)
_______ is the final step in the degradation of purines. this has no physiological purpose, and it is a waste product.
uric acid
our body makes these endogenously and we can also get them exogenously from food; makes up building blocks of DNA and RNA.
purines
hyperuricemia will occur when there is either _______ or ________ of uric acid
overproduction or under excretion
this is the less common cause of hyperuricemia; is occurs when there is an issue with the enzyme systems that regulate purine metabolism (increase in PRPP synthase which is a key determinant of purine synthesis in the body and a decrease in HGPRT); usually seen in blood cancers where there is an excessive rate of cell turnover
overproduction of uric acid
this is a more common cause of hyperuricemia and gout; 90% of gout patients have a relative decrease in the renal excretion of uric acid for an unknown reason; sodium reapsorbtion may also be linked to this (dehydration - body saves Na which in turn saves uric acid and therefore not as much is excreted); drug can also hinder excretion
under excretion of uric acid
what are some common drugs than can modify filtration or uric acid or alter reabsorption
- alcohol
- cyclosporines
- diuretics: thiazide (HCTZ, chlorthalidone and indapamide) and loop (furosemide)
- tacrolimus
what are the 4 different clinical spectrums of gout?
- asymptomatic hyperuricemia
- acute gouty arthritis (gouty flare)
- intercritical gout (prophylaxis of flares)
- chronic gouty arthritis
this is not an indication for uric acid lowering therapy
- try to identify possible cause and eliminate medications that could be contributing
- encourage lifestyle modifications
asymptomatic hyperuricemia
this is a rapid localized onset of excruciating pain, swelling and inflammation. the attack is usually monoarticular - most often in the metatarsophalangeal joint (big toe)
insteps > ankles>heels>knees>wrists>fingers>elbows
fever and elevated WBCs may be seen
acute gouty arthritis (gouty flare)
does this describe a presumptive or definitive diagnosis?
for typical presentation clinical diagnosis is alone reasonable (elevated serum uric acid + inflammation/pain of the big toe)
presumptive diagnosis
does this describe a presumptive or definitive diagnosis?
presence of crystals in the synovial fluid
definitive diagnosis
treatment for an acute episode of gout should be treated within ____ hours of symptom onset
24
what are the three options for treating an acute episode of gout?
- nsaids
- colchicine
- corticosteroids
ture/false: treatment options (e.g. NSAIDS, colchicine and corticosteroids) can be combined in order to treat an acute episode of gout in those with severe gout
true BUT avoid the use of an oral steroid + NSAID due to increased risk of GI adverse effects
true/false: you should not use NSAIDs concomitantly, even with low dose aspirin
false - can use with appropriately indicated low dose ASA
what are the most commonly used NSAIDs for gout?
indomethacin
naproxen
ibuprofen
celecoxib
if a patient is taking an NSAID for an acute gout flare, how long after starting the NSAID should they wait to see a HCP if the pain doesn’t get better
5-8 days
this medication is only effective if its started within 36 hours of symptoms, with the greatest efficacy seen in the first 24 hours of symptom onset
colchicine
what is the dosing for a otherwise healthy patient of colchicine
1.6mg stat, then 0.6mg 1 hour later. then in 12 hours 0.6mg daily or BID until gout attack is resolved
what is the dose of colchicine for elderly patients with decreased renal function or patients of p-glycoprotein inhibitors
0.6mg stat then 0.3mg PO every other day
what are some common adverse effects of colchicine
n/v, abdominal pain and cramps, diarrhea
what are some rare side effects of colchicine
neuropathy, myopathy, bone marrow suppression
Colchicine may interact with ______ as it may increase HMG-CoA reductase inhibitors - monitor for muscle pain & weakness
statins
decrease dose and monitor for colchicine toxicity (e.g. GI symptoms, fever, leukopenia) if also taking known inhibitors of ______ (e.g. antiretrovirals, macrolides, itraconazole, ketoconazole, verapamil) or p-glycoprotein inhibitors (e.g. cyclosporine)
cyp3A4
what is an auxiliary label + counselling point for patients when taking colchicine (dietary)
avoid grapefruit juice
this medication for an acute gout flare is usually reserved for patients who can’t take NSAIDs or can tolerate colchicine/it doesn’t work.
corticosteroids
what are some non-pharmacological measures for patients regarding prophylaxis of gout attacks
- switch/eliminate medications that induce hyperuricemia
- encourage weight loss
- limit alcohol intake (especially avoid during acute attacks or if gout is poorly controlled)
- exercise regular
- smoking cessation
- avoid organ meats high in protein (e.g. liver, kidney)
- avoid food and beverages high in fructose and corn syrup
- limit intake of beef, lamb, pork &n seafood high in purines (sardines and shellfish)
- limit consumption of table salt, table sugar and desserts
- encourage low fat or non-fat dairy products
when is urate lowering therapy (ULT) indicated?
- more than 2 gout attacks per year
- presence of tophus/tophi
- presence or history of uric acid stones
- reduced kidney function (Cr less than 90 mL/min)
this is the first line choice. when starting it, you should START LOW AND GO SLOW.
allopurinol
allopurinol is started off at 100mg in an otherwise healthy individual. at what intervals should the dose be increased if necessary
q 2-4 weeks
what is the maximum daily dose in allopurinol
800mg/day - should be in divided doses to decrease GI side effects
what patients are at an increased risk of a hypersensitivity reaction
elderly, those with chronic kidney disease or hepatic impairment
true/false: Allopurinol should be dose reduced in those with renal impairment
true
what are some common (not serious) adverse effects of allopurinol
- maculopapular skin rash (non-life threatening - only seen in ~ 2% of patients)
- GI upset (Take with food)
- can precipitate a gout attack
what are some serious adverse effects of allopurinol
- Skin reactions usually accompanied by fever, eosinophilia, hepatic and renal dysfunction and rash such as:
1. allopurinol hypersensitivity syndrome
2. Steven-Johnson syndrome
3. toxic epidermal necrosis
4. drug rash with eosinophilia & systemic symptoms (DRESS)
if a patient experiences a itchy rash when taking allopurinol, what should you advise the patient to do?
stop taking the drug and contact HCP immediately
what are some medications that interact with allopurinol?
- azathioprine & mercaptopurine - thiopurine toxicity = bone marrow suppression
- amoxicillin/ampicillin (maculopapular rash)
- thiazides (maculopapular rash)
- antacids (maculopapular rash)
- ACEi (maculopapular rash)
- warfarin (increased INR)
- cyclophosphamide (oncology drug - increased risk for toxicity)
this prophylaxis agent is usually used in patients with renal insufficiency or if desired symptom control is not achieved with allopurinol; significantly more expensive that allopurinol
febuxostat (ULORIC)
true/false: febuxostat needs to be adjusted for those with compromised renal function
false - no adjustment necessary for those with compromised renal function, but there is no information on use in those with renal function less than 30ml/min
true/false: febuxostat may cause more acute gout flares during initiation than allopurinol
true
what drug interactions are there with febuxostat
- azathioprine & mercaptopurine (contraindicated)
what are some adverse effects associated with febuxostat?
- abnormalities in LFTs
- GI upset (N/D)
- skin rash at higher doses (not life threatening)
- may increase risk of MI & stroke?
what should be monitored when patients are started on allopurinol and febuxostat?
- Uric acid levels and renal function
every 2-4 weeks during dose titration and then every 3-6 months after target reached
if on febuxostat, LFTs should be monitored every 2-4 months and then periodically
this prophylaxis agent increases the renal clearance of uric acid by inhibiting renal tubular reabsorption of uric acid; the use of this class of drugs should be avoided in patients with a history of urolithiasis (formation of stony concretions in the bladder or urinary tract) and if their CrCL is < 50 mL/min
uricosuric agents
this prophylaxis agents is a uricosuric agent that is usually only used when allopurinol/febuxostat therapy has failed or is contraindicated. it is only available throughout the healthy Canada special access program
probenecid
these two medications have been used adjectivally with xanthine oxidase inhibitors (allopurinol and febuxostat) for prophylaxis of gout
fenofibrate and Losartan
if a patient has renal impairment (CrCl < 90ml/min) what should be used and what should be avoided for acute treatment
- colchicine and corticosteroids preferred
-avoid NSAIDs
if a patient has renal impairment (CrCl < 90ml/min) what should be used for prophylaxis treatment and are dosage adjustments necessary?
- allopurinol: dosage adjustment with severe kidney disease
- febuxostat: no dosage adjustment necessary if CrCl 30-90 ml/min
if a patient has cardiovascular comorbidities, what should be used and what should be avoided for acute treatment
- colchicine preferred
- avoid NSAIDs and avoid steroids in patients with heart failure
- remember if pt has high blood pressure, and NSAIDs are acute tx - MONITOR BP
if a patient has cardiovascular comorbidities, what should be used and what should be avoided for prophylaxis therapy?
- based on CARES trial? avoid febuxostat
- allopurinol should be started at a low dose (50mg) and titrated slowly
