Gout-DUan Flashcards
What is the pH like in synovial tissues & leukocytes in patients with gout?
low pH b/c of high lactate production associated with inflammation
the low pH fosters further deposition of uric acid
What is the relationship w/ gout & kidneys?
uric acid as urate can be deposited in kidney & become kidney stones
Uric acid is positively correlated with which features in men?
height weight BUN/Creatinine BP Diabetes, Hyperlipidemia, Alcohol Consumption Warm Climate Social Status Intelligence
Which demographic has the highest prevalence of gout?
Men in their 70s
10% of them!
Describe the process of purine metabolism.
AMP–IMP–>Hypoxanthine–>Xanthine–>Uric Acid–>Urate
What is the enzyme that turns AMP to IMP in purine metabolism?
adenylate deaminase
What is the enzyme that recycles hypoxanthine back into IMP?
HPRT: hypoxanthine-guanine phosphoribosyl transferase
need this to work so that you don’t end up with quite as much uric acid!
What are the 2 forms of primary gout?
Adenosine deaminase deficiency
associated with SCID
HPRT deficiency associated with Lesch-Nyhan syndrome
What are the features associated with adenosine deaminase deficiency & SCID?
self mutilation
spasticity
choreoathetosis
retardation
What are the features associated with X-linked Lesch-Nyhan syndrome & HPRT deficiency?
hyperuricemia
nephrolithiasis
gout
What are normal uric acid levels in men? women?
Men: 3.4-7
women: 2.4-6
What are the 2 main categories of secondary gout?
Overproduction
Underexcretion
What are some ways that you can get overproduction of uric acid leading to secondary gout?
increased breakdown of blood cells–leukemia
chemo or radiation
What are some ways that you can get under excretion of uric acid leading to secondary gout?
alcohol use
thiazide diuretic
low dose aspirin
What is the disease progression of gout?
Asymptomatic Hyperuricemia Acute Gout Intercritical Period Chronic Tophaceous Gout Nephrolithiasis: kidney stones
What is the level of serum urate during asymptomatic hyperuricemia?
7mg/dl
people at risk for developing gout, but haven’t yet.
What happens during the acute gout phase?
painful monoarticular arthritis
usu in 1st metatarsal joint
What happens during the inter critical period in gout?
remission for indeterminate length
What happens when you are experiencing chronic tophaceous gout?
gouty arthritis crystals in synovium chalky mass called tophus erosion of bone **caused by continued precipitation of sodium urate crystals during attacks of acute gout
What is colchicine used for? How fast does it work?
acute gout attacks
relieves pain 12-24 hrs after oral administration
T/F The MOA of colchicine includes increased renal excretion of uric acid, changing the serum concentration of urate.
False. This is NOT its MOA.
What do we know about the MOA of colchicine?
binds to tubulin, messes with mitotic spindles
depolymerization of microtubules in granulocytes
inhibits granulocytes from migrating to inflamed area & goin’ crazy
less release of lactic acid
INHIBITS the release of histamine granules from mast cells
How is colchicine metabolized & excreted?
metabolized by CYP3A4 in liver
excreted in feces (mostly)
a little in urine
Most patients experience adverse side effects when taking colchicine. What are they?
nausea vomiting abdominal pain diarrhea IV admin reduces this rare cases: liver damage
What is the MOA of uricosuric agents? What are 3 examples? Which one is also an NSAID?
**increase excretion of uric acid by kidneys by blocking its reabsorption
Probenecid
Sulfinpyrazone (NSAID)
Benzbromarone
When should you use probenecid or sulfinpyrazone for gout?
when it is chronic gout
can be used in combo with colchicine
What is one of the tricky things about taking probenecid & sulfinpyrazone with other meds when treating gout?
inhibit the excretion of other drugs that are secreted by renal tubules like penicillin, NSAIDs, cephalosporins, methotrexate
What are some of the adverse side effects of probenecid & sulfinpyrazone? How can one of these be avoided?
kidney stones (potassium citrate-alkalinzation of urine or drink lots of water)
GI
dermatitis
What is another name for allopurinol? WHat is its MOA for treating gout?
zyloprim
inhibits the synthesis of uric acid by inhibiting xanthine oxidase
What are the common side effects of allopurinol? When should you NOT use it?
GI; dermatitis
not with patients who have liver disease or bone marrow depression
What are the FDA approved NSAIDs to use with gout?
indomethacin
naproxen
sulindac
T/F Corticosteroids are a frequently used & helpful treatment option for gout.
False. Usu not used.
Febuxostate aka uloric is a treatment for gout. How does it work?
lowers uric acid levels
non-purine inhibitor of uric acid by forming a complex with an enzyme
HOw is febuxostate aka uloric eliminated? WHat is its half life?
metabolized by CYP2C9
renal & hepatic elimination
t1/2=5-8 hrs
When do you use febuxostate aka uloric? What are its potential side effects?
used for attacks, not for when patients are asymptomatic
liver toxicity & cardio problems are major side effects
What is rasburicase aka elitek?
pediatric management of uric acid
usu for patients receiving chemo or experiencing tumor lysis syndrome–often experience hyperuricemia with cell turnover
What is used to treat acute gout?
nonsalicylate NSAIDs (indomethacin, naproxne, sulindac) sometimes colchicine for a few weeks
What is used to treat chronic gout?
uricosuric agents (probenecid & sulfinpyrazone) \+allopurinol
What are maintenance drugs for patients with gout?
allopurinol, probenecid, sulfinpyrazone
