4. Gout MT1

Question 1

this is an inflammatory disease associated with the deposition of monosodium urate crystals (MSU) in joints and soft tissues due to chronic hyperuricemia

Answer 1

gout

Question 2

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

Answer 2

hyperuricemia

Question 3

true/false: sustained elevation of serum urate is essential for the development of gout, but hyperuricemia does not always lead to gout

Answer 3

true

Question 4

what are some risk factors for developing gout?

Answer 4

• male gender
• increased age
• obesity, sedentary lifestyle
• consumption of alcohol, surgery beverages, and red meat (food high in purines)

Question 5

_______ is the final step in the degradation of purines. this has no physiological purpose, and it is a waste product.

Answer 5

uric acid

Question 6

our body makes these endogenously and we can also get them exogenously from food; makes up building blocks of DNA and RNA.

Answer 6

purines

Question 7

hyperuricemia will occur when there is either _______ or ________ of uric acid

Answer 7

overproduction or under excretion

Question 8

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

Answer 8

overproduction of uric acid

Question 9

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

Answer 9

under excretion of uric acid

Question 10

what are some common drugs than can modify filtration or uric acid or alter reabsorption

Answer 10

• alcohol
• cyclosporines
• diuretics: thiazide (HCTZ, chlorthalidone and indapamide) and loop (furosemide)
• tacrolimus

Question 11

what are the 4 different clinical spectrums of gout?

Answer 11

• asymptomatic hyperuricemia
• acute gouty arthritis (gouty flare)
• intercritical gout (prophylaxis of flares)
• chronic gouty arthritis

Question 12

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

Answer 12

asymptomatic hyperuricemia

Question 13

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

Answer 13

acute gouty arthritis (gouty flare)

Question 14

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)

Answer 14

presumptive diagnosis

Question 15

does this describe a presumptive or definitive diagnosis?
presence of crystals in the synovial fluid

Answer 15

definitive diagnosis

Question 16

treatment for an acute episode of gout should be treated within ____ hours of symptom onset

Answer 16

24

Question 17

what are the three options for treating an acute episode of gout?

Answer 17

• nsaids
• colchicine
• corticosteroids

Question 18

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

Answer 18

true BUT avoid the use of an oral steroid + NSAID due to increased risk of GI adverse effects

Question 19

true/false: you should not use NSAIDs concomitantly, even with low dose aspirin

Answer 19

false - can use with appropriately indicated low dose ASA

Question 20

what are the most commonly used NSAIDs for gout?

Answer 20

indomethacin
naproxen
ibuprofen
celecoxib

Question 21

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

Answer 21

5-8 days

Question 22

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

Answer 22

colchicine

Question 23

what is the dosing for a otherwise healthy patient of colchicine

Answer 23

1.6mg stat, then 0.6mg 1 hour later. then in 12 hours 0.6mg daily or BID until gout attack is resolved

Question 24

what is the dose of colchicine for elderly patients with decreased renal function or patients of p-glycoprotein inhibitors

Answer 24

0.6mg stat then 0.3mg PO every other day

Question 25

what are some common adverse effects of colchicine

Answer 25

n/v, abdominal pain and cramps, diarrhea

Question 26

what are some rare side effects of colchicine

Answer 26

neuropathy, myopathy, bone marrow suppression

Question 27

Colchicine may interact with ______ as it may increase HMG-CoA reductase inhibitors - monitor for muscle pain & weakness

Answer 27

statins

Question 28

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)

Answer 28

cyp3A4

Question 29

what is an auxiliary label + counselling point for patients when taking colchicine (dietary)

Answer 29

avoid grapefruit juice

Question 30

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.

Answer 30

corticosteroids

Question 31

what are some non-pharmacological measures for patients regarding prophylaxis of gout attacks

Answer 31

- 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

Question 32

when is urate lowering therapy (ULT) indicated?

Answer 32

- 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)

Question 33

this is the first line choice. when starting it, you should START LOW AND GO SLOW.

Answer 33

allopurinol

Question 34

allopurinol is started off at 100mg in an otherwise healthy individual. at what intervals should the dose be increased if necessary

Answer 34

q 2-4 weeks

Question 35

what is the maximum daily dose in allopurinol

Answer 35

800mg/day - should be in divided doses to decrease GI side effects

Question 36

what patients are at an increased risk of a hypersensitivity reaction

Answer 36

elderly, those with chronic kidney disease or hepatic impairment

Question 37

true/false: Allopurinol should be dose reduced in those with renal impairment

Answer 37

true

Question 38

what are some common (not serious) adverse effects of allopurinol

Answer 38

- maculopapular skin rash (non-life threatening - only seen in ~ 2% of patients) - GI upset (Take with food) - can precipitate a gout attack

Question 39

what are some serious adverse effects of allopurinol

Answer 39

- 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)

Question 40

if a patient experiences a itchy rash when taking allopurinol, what should you advise the patient to do?

Answer 40

stop taking the drug and contact HCP immediately

Question 41

what are some medications that interact with allopurinol?

Answer 41

- 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)

Question 42

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

Answer 42

febuxostat (ULORIC)

Question 43

true/false: febuxostat needs to be adjusted for those with compromised renal function

Answer 43

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

Question 44

true/false: febuxostat may cause more acute gout flares during initiation than allopurinol

Answer 44

true

Question 45

what drug interactions are there with febuxostat

Answer 45

- azathioprine & mercaptopurine (contraindicated)

Question 46

what are some adverse effects associated with febuxostat?

Answer 46

- abnormalities in LFTs - GI upset (N/D) - skin rash at higher doses (not life threatening) - may increase risk of MI & stroke?

Question 47

what should be monitored when patients are started on allopurinol and febuxostat?

Answer 47

- 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

Question 48

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

Answer 48

uricosuric agents

Question 49

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

Answer 49

probenecid

Question 50

these two medications have been used adjectivally with xanthine oxidase inhibitors (allopurinol and febuxostat) for prophylaxis of gout

Answer 50

fenofibrate and Losartan

Question 51

if a patient has renal impairment (CrCl < 90ml/min) what should be used and what should be avoided for acute treatment

Answer 51

- colchicine and corticosteroids preferred -avoid NSAIDs

Question 52

if a patient has renal impairment (CrCl < 90ml/min) what should be used for prophylaxis treatment and are dosage adjustments necessary?

Answer 52

- allopurinol: dosage adjustment with severe kidney disease - febuxostat: no dosage adjustment necessary if CrCl 30-90 ml/min

Question 53

if a patient has cardiovascular comorbidities, what should be used and what should be avoided for acute treatment

Answer 53

- 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

Question 54

if a patient has cardiovascular comorbidities, what should be used and what should be avoided for prophylaxis therapy?

Answer 54

- based on CARES trial? avoid febuxostat - allopurinol should be started at a low dose (50mg) and titrated slowly