Gout EXAM 4 Flashcards by o e

What is the Pathophysiology of Gout?

inflammatory arthritis caused by hyperuricemia crystal deposition in joints and tissues

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Which drugs can worsen Gout or lead to an acute gout flare?

-diuretics
-low-dose aspririn (still use it if indicated)
-cyclosporin, tacrolismus

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Which dietary components can trigger or worsen a gout flare?

-excess Alcohol (especially beer and spirits)
-non-diet sodas
-high fructose corn syrup

purine-rich foods
-red meat
-shellfish

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What is the MOA of Allopurinol?

Xanthine Oxidase inhibitors

blocks the conversion of hypoxanthine -> xanthine -> uric acid

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What is the common dose of Allopurinol for gout treatment?

What is the goal serum urate level?

start with 100 mg daily !! (risk for hypersensitivity if starter too high)
then: 100-800 mg daily

goal urate concentration <6 mg/dl

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What is the starting dose of allopurinol for patients with CKD stage 3 or higher or CrCl <30?

50 mg daily

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Which side effects are associated with Allopurinol?

alllopurinol hypersensitivity syndrome
-severe rash (epidermal necrolysis, erythema multiforme, dermatitis)
-hepatitis
-interstitial nephritis
-eosinophilia (high eosinophil level)

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Which DDI are associated with Allopurinol?

Azathioprine & 6-Mercaptopurine (6-MP)
Warfarin
Cyclophosphamide

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Which patients are at higher risk for allopurinol hypersensitivity syndrome?

-female
-age over 60y
-allopurinol starting dose more than 100 mg/daily
-using allopurinol for asymptomatic hyperuricemia
-kidney disease
-CVD
-HLA-B*5801 allele

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What is required before starting Allopurinol?

HLA-B*5801 allele testing

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What is the brand name of Allopurinol?

Lopurin, Zyloprim

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What is the MOA of Febuxostat?

Xanthine Oxidase inhibitors

blocks the conversion of hypoxanthine -> xanthine -> uric acid

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What is the brand name of Febuxostat?

Uloric

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What are the side effects of Febuxostat?

Liver enzymes elevation
nausea
arthralgia
rash

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What are the common DDis of Febuxostat?

Azathioprine
6-MP

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In which patient population should febuxostat be avoided?

What does the BBW say?

patients with cardiovascular disease
-due to increased all-cause mortality

FDA Black Box warning:
-reserve Febuxostat for patients who can’t tolerate allopurinol

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What is the dose of Febuxostat for Hyperuremic treatment in gout?

start with 40 mg daily
then 40-80 mg daily

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What is the MOA of Probenecid?

increases the elimination of uric acid
uricosuric agent

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What is the brand name of Probenecid?

Probalan

What is the dose of Probenecid in Hyperuricemia treatment?

250 mg BID for 1 week
then 500-2000 mg daily

target serum urate <6 mg/dl

What are the side effects of Probenecid?

-Urolithiasis (kidney stone)
-GI irritation
-rash/hypersensitivity
-gouty arthritis

What are the DDIs of Probenecid?

Aspirin (interferes with the MOA of Probenecid -> treatment failure; may use baby aspirin with caution)

reduced excretion:
-Penicillin
-Cephalosporins
-Sulfonamides
-Indomethacin

Methotrexate

Who should avoid Probenecid?

patients with a history of kidney impairment
counsel on sufficient fluid intake

What are the side effects of NSAIDs?

GI bleeding
kidney injury
sodium and fluid retention -> HTN
headache

What are the side effects of Corticosteroids?

-injection pain -rebound arthritis -osteoporosis -Hypothalamic–pituitary axis suppression -cataracts -muscle deconditioning -can worsen diabetes -GI problems -bleeding need taper if d/c

Which of the following has a risk for rebound gout flare when stopping steroid therapy? Systemic steroid administration Intraarticular (into the joint) administration

Systemic administration -> therefore need taper !!

What is the dose of prednisone when used for acute gout?

<10 mg daily

What is the MOA of Colchicine?

prevents microtubule polymerization in neutrophils -> reduces neutrophil migration into inflamed joints

What is the dose of Colchicine?

1.2 mg initially -> 0.6 mg 1hour later

What is the brand name of Colchicine?

Colcrys

What are the side effects of Colchicine?

dosedependent: -GI adverse effects: including nausea, vomiting, and diarrhea -neutropenia -axonal neuromyopathy (worse when taken with statin, or kidney dysfunction)

What is the MOA of Pegloticase?

Recombinant uricase -hydrolyzes uric acid to allantoin

What are the side effects of Pegloticase?

infusion reaction anaphylaxis patients need treatment with antihistamines and corticosteroids before therapy -IV infusion 2x week given over 2h

What is the place in therapy for Pegloticase?

severe gout and hyperuricemia (>8 mg/dl) who have failed or have contraindication to allopurionol

What is the place in therapy for intra-articular or intramuscular corticosteroids?

intraarticular: acute gout on one or two joints intramuscular: for patients with multiple affected joints who are unable to take oral therapy

Which drugs are used for acute gout (gout flares)?

1st line: NSAIDs -Indomethacin -Naproxen -Sulindac may use Corticosteroids

What is the dose of Indomethacin for Gout?

50 mg TID

What is the dose of Naproxen for Gout?

750 mg followed by 250 mg every 8 hours until the attack has subsided

What is the initial dose for Ibuprofen?

400 mg TID

After how many gout episodes is Urate-lowering treatment (ULT) indicated based on the ACR guidelines? What are other indications for ULT

2 or more attacks per year others: -the presence of 1 or more tophus and radiographic evidence of damage caused by gout tophus: deposit of monosodium urate (MSU) crystals

Which conditions require shared decision-making before starting gout treatment?

-more than 1 gout attack with infrequent flares (less than 2x a year) -1st flare with CKD (stage 3 or higher), uric acid level >9 mg/dl -Urolithiasis (kidney stone)

What is the 1st line therapy for Hyperuricemia in Gout?

Allopurinol 2nd line: Febuxostat 3rd line: Xanthin inhibitor + uricosuric agent (probenecid) Last line: pegloticase

How do we treat gout in patients with impaired renal function?

-allopurinol or febuxostat -> if it doesn't work try pegloticase -reduced dose of colchicine or corticosteroids (short-term for acute gout) avoid NSAIDs, Uricosurics (probenecid), Lesiurad

How do we treat gout in patients with GI disease?

-corticosteroids (intraarticular if only joint is affected -Colchicine can cause GI upset and diarrhea -NSAIDs increase risk of GI bleeding or ulceration

How do we treat gout in patients with heart failure and HTN?

-colchicine for acute gout or prophylaxis -may use losartan for HF or HTN due to is uricosuric properties -avoid NSAIDs and diuretics (increases serum urate) -if a diuretic is necessary, initiate allopurinol

Which drugs are used in patients who use CYP3A4 inhibitors or P-glycoprotein inhibitors? Name common P-glycoprotein inhibitors.

-NSAIDs or corticosteroid are preferred DDI between CYPs and colchicine (so dose-adjust) P-glycoprotein inhibitors: -Cyclosporine, Ranolazine