Rx Gout Flashcards
what level of urate is considered hyperuriemia?
> 6.8 mg/dL
Patients can be hyperuricemic may not develop clinical gout symptoms - the treatment of leukemia and lymphomas increase the risk of hyperuricemia and gout.
Characteristics of chronic gouty arthritis include
Uric acid deposits in the kidney
Tophi - deposits in the skin
Gout pathophysiology
Purine metabolism -> urate crystals
Most gout patients are under-excretors
The crystals trigger neutrophils and an inflammatory response
which gender is gout more common in?
Male - 6.9% prevalence
Female - 2% prevalence
What type of substances reduce excretion of uric acid?
diuretics - loop and thiazides
nicotinic acid
Salicylates at 2g per day (hard to meet) - a gout patient with MI history should stay on their aspirin
Calcineurin inhibitors - cyclospoine, tacrolimus (immunosuppressive drugs)
explain the inflammation associated with Gout
happens 10-30 years after asymptomatic hyperuricemia
urate crystals are ingested by macrophages and synoviocytes, this leads to the activation of NLRP3 inflammasome and secretion of Il-1beta
Neutrophils are recruited, the major driving force on inflammation.
crystals of uric acid
needle-like
negatively birefringent
Acute Gouty Arthritis
usually in the first MTP joint - podagra - can also affect other joints of the lower limbs
can be accompanied by fever, chills and malaise
inflammation resolves spontaneously over 10 to 14 days
serum uric acid may not be elevated during an acute episode
Chronic Gouty Arthritis
tophi - larger aggregates of Uric acid crystal deposition (in skin). Can grow between attacked.
Chronic inflammation erodes bone and cartilage - appear like osteoarthritis
10 or more years after acute intermittent gout
it’s chronic gout when the inbetween periods are no longer pain free
kidney damage
kidneys and gout - what is the damage?
nephrolithiasis
stones - some uric acid stones, calcium stones are 10x more common in gout patients
what type of things should gout patients avoid?
avoid organ meats, high fructose corn syrup, and when uncontrolled - alcohol
what type of things should gout patients limit?
servings of beef, pork, lamb, sardines and shellfish
servings of naturally sweet fruit juices
sugar, salt
alcohol
whats the first line treatment of acute gout?
NSAIDS
Corticosteriods - has many side effects, not preferred
colchicine - anti-gout, anti-inflammatory
ACTH
main therapeutic goal is to control inflammation
Urate-lowering therapy
aim to reduce serum uric acid
xanthine oxidase inhibitors - allopurinol and febuxostat
uricosuric drugs - Probenecid, (sulfinpyrazone), lesinurad
what is transition therapy in gout?
administration of anti-inflammatory and ULT
If a patient is on ULT and has an acute attack how should their prescription change?
ULT should not be discontinued but the anti-inflammatory should be added on
NSAIDs
MOA - inhibits prostaglandin synthesis and urate crystal phagocytoses
used for acute management of gout
toxicties include GI ulcers and bleeding
can be poorly tolerated in elderly, renal insufficiency or GI disorders.
Corticosteroids
MOA - suppression of immune response
used for the acute management of gout and also 2nd line for transition to ULT
toxicities - insomnia, mood changes, hyperglycemia and fluid retention
gout requires a larger dose, oral is most common
Colchicine
MOA - inhibits inflammatory response by inhibiting microtubule polymerization
clinical use - acute management of gout, transition, rarely long lerm propholaxis
toxicities - nausea, vomiting, diarrhea; continued use leads to neuropathy and bone marrow suppression
A LOT of drug interactions
Rx needs to be initiated within 36 hours of onset
ACTH
for patients that cannot take oral therapy
25-40 IU subQ
expensive
what are the common doses for NSAIDs when treating Gout?
Indomethacin 50 mg 3 times daily
Naproxen 750 mg at first, then 3 times daily
Ibuprofen 800 mg three times a day
Dosage of Colchicine
- 2 mg starting dose
0. 6 mg in an hour
treatment for severe acute attack
Gout - combination therapy for intense pain or polyarticular
colchicine + NSAIDs
colchicine + oral steroids
intra-articular steroids + anything
NSAIDS and Oral Steroids should NOT be prescribed because of synergistic GI toxicities
What are the indications for ULT?
An established dx of Gout and:
Tophi
frequent attacks
Chronic Kidney Disease - stage 2
History of urolithiasis
when should ULT be started?
After an acute attack has resolved or during asymptomatic periods
goal is for serum urate is < 6mg/dL
initiation of prophylaxis
first line is low dose colchicine and NSADS
second line is low dose prednisone
treatment for at least 6 mo, depends on finding on PE
Allopurinol - MOA, Use and Metabolism
MOA - reduces uric acid formation through competitive inhibition of xanthine oxidase
used for the chronic management of gout or cancer related hyperuricemia
metabolized to oxypurinol, which also inhibits xanthine oxidase
Febuxostat
MOA - nonpurine inhibitor of xanthine oxidase
for chronic management of gout
inactive metabolite - no renal adjustments
Uricosuric agents
compete with uric acid for the transporter which inhibits reabsorption, avoid in uric acid over-produces
Probenecid
used for chronic management of gout
causes rash, precipitation of gouty arthritis and nephrolithiasis
Lesinurad
Required to be given with Allopurinol
MOA - inhibits URAT1 and OAT4
used for hyperuricemia
toxicities- headache, increased serum creatine and GERD
interacts with CYP2C9 inhibitors and CYP2C9 inducers and REDUCES EFFICACY OF HORMONAL CONTRACEPTIVES
Allopurinol - toxicities, dose, drug interactions and monitorings
toxicities - dyspepsia, headache, diarrhea and pruritic maculopapular rash
hypersensitivity - HLAB58:01
initial dose - 100 mg/day, titrate as needed, adjust in renal insuffeiciency
interacts with acathioprine and mercaptopurine (immunosuppresants)
monitor liver function and serum creatinine and CBC
Febuxostat - toxicities
toxicities - nausea, msk pain, rash, increased risk for thromboembolic events in patients with history of CV events
Febuxostat - toxicities and interactions
toxicities - nausea, msk pain, rash, increased risk for thromboembolic events in patients with history of CV events
interacts with azathioprine and mercaptopurine
IL-1 Inhibitors
Anakinra
Rilonacept
Canakinumab
alternatives for gout …. somehow.
Uricase
pegloticase
Rasburicase
enzyme for digesting uric acid
