Gout EXAM 4 Flashcards
What is the Pathophysiology of Gout?
inflammatory arthritis caused by hyperuricemia crystal deposition in joints and tissues
Which drugs can worsen Gout or lead to an acute gout flare?
-diuretics
-low-dose aspririn (still use it if indicated)
-cyclosporin, tacrolismus
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
What is the MOA of Allopurinol?
Xanthine Oxidase inhibitors
blocks the conversion of hypoxanthine -> xanthine -> uric acid
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
What is the starting dose of allopurinol for patients with CKD stage 3 or higher or CrCl <30?
50 mg daily
Which side effects are associated with Allopurinol?
alllopurinol hypersensitivity syndrome
-severe rash (epidermal necrolysis, erythema multiforme, dermatitis)
-hepatitis
-interstitial nephritis
-eosinophilia (high eosinophil level)
Which DDI are associated with Allopurinol?
Azathioprine & 6-Mercaptopurine (6-MP)
Warfarin
Cyclophosphamide
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
What is required before starting Allopurinol?
HLA-B*5801 allele testing
What is the brand name of Allopurinol?
Lopurin, Zyloprim
What is the MOA of Febuxostat?
Xanthine Oxidase inhibitors
blocks the conversion of hypoxanthine -> xanthine -> uric acid
What is the brand name of Febuxostat?
Uloric
What are the side effects of Febuxostat?
Liver enzymes elevation
nausea
arthralgia
rash
What are the common DDis of Febuxostat?
Azathioprine
6-MP
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
What is the dose of Febuxostat for Hyperuremic treatment in gout?
start with 40 mg daily
then 40-80 mg daily
What is the MOA of Probenecid?
increases the elimination of uric acid
uricosuric agent
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
