Gout-DUan Flashcards

1
Q

What is the pH like in synovial tissues & leukocytes in patients with gout?

A

low pH b/c of high lactate production associated with inflammation
the low pH fosters further deposition of uric acid

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2
Q

What is the relationship w/ gout & kidneys?

A

uric acid as urate can be deposited in kidney & become kidney stones

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3
Q

Uric acid is positively correlated with which features in men?

A
height
weight
BUN/Creatinine
BP
Diabetes, Hyperlipidemia, Alcohol Consumption
Warm Climate 
Social Status
Intelligence
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4
Q

Which demographic has the highest prevalence of gout?

A

Men in their 70s

10% of them!

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5
Q

Describe the process of purine metabolism.

A

AMP–IMP–>Hypoxanthine–>Xanthine–>Uric Acid–>Urate

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6
Q

What is the enzyme that turns AMP to IMP in purine metabolism?

A

adenylate deaminase

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7
Q

What is the enzyme that recycles hypoxanthine back into IMP?

A

HPRT: hypoxanthine-guanine phosphoribosyl transferase

need this to work so that you don’t end up with quite as much uric acid!

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8
Q

What are the 2 forms of primary gout?

A

Adenosine deaminase deficiency
associated with SCID
HPRT deficiency associated with Lesch-Nyhan syndrome

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9
Q

What are the features associated with adenosine deaminase deficiency & SCID?

A

self mutilation
spasticity
choreoathetosis
retardation

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10
Q

What are the features associated with X-linked Lesch-Nyhan syndrome & HPRT deficiency?

A

hyperuricemia
nephrolithiasis
gout

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11
Q

What are normal uric acid levels in men? women?

A

Men: 3.4-7
women: 2.4-6

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12
Q

What are the 2 main categories of secondary gout?

A

Overproduction

Underexcretion

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13
Q

What are some ways that you can get overproduction of uric acid leading to secondary gout?

A

increased breakdown of blood cells–leukemia

chemo or radiation

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14
Q

What are some ways that you can get under excretion of uric acid leading to secondary gout?

A

alcohol use
thiazide diuretic
low dose aspirin

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15
Q

What is the disease progression of gout?

A
Asymptomatic Hyperuricemia
Acute Gout
Intercritical Period
Chronic Tophaceous Gout
Nephrolithiasis: kidney stones
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16
Q

What is the level of serum urate during asymptomatic hyperuricemia?

A

7mg/dl

people at risk for developing gout, but haven’t yet.

17
Q

What happens during the acute gout phase?

A

painful monoarticular arthritis

usu in 1st metatarsal joint

18
Q

What happens during the inter critical period in gout?

A

remission for indeterminate length

19
Q

What happens when you are experiencing chronic tophaceous gout?

A
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
20
Q

What is colchicine used for? How fast does it work?

A

acute gout attacks

relieves pain 12-24 hrs after oral administration

21
Q

T/F The MOA of colchicine includes increased renal excretion of uric acid, changing the serum concentration of urate.

A

False. This is NOT its MOA.

22
Q

What do we know about the MOA of colchicine?

A

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

23
Q

How is colchicine metabolized & excreted?

A

metabolized by CYP3A4 in liver
excreted in feces (mostly)
a little in urine

24
Q

Most patients experience adverse side effects when taking colchicine. What are they?

A
nausea
vomiting
abdominal pain
diarrhea
IV admin reduces this
rare cases: liver damage
25
Q

What is the MOA of uricosuric agents? What are 3 examples? Which one is also an NSAID?

A

**increase excretion of uric acid by kidneys by blocking its reabsorption
Probenecid
Sulfinpyrazone (NSAID)
Benzbromarone

26
Q

When should you use probenecid or sulfinpyrazone for gout?

A

when it is chronic gout

can be used in combo with colchicine

27
Q

What is one of the tricky things about taking probenecid & sulfinpyrazone with other meds when treating gout?

A

inhibit the excretion of other drugs that are secreted by renal tubules like penicillin, NSAIDs, cephalosporins, methotrexate

28
Q

What are some of the adverse side effects of probenecid & sulfinpyrazone? How can one of these be avoided?

A

kidney stones (potassium citrate-alkalinzation of urine or drink lots of water)
GI
dermatitis

29
Q

What is another name for allopurinol? WHat is its MOA for treating gout?

A

zyloprim

inhibits the synthesis of uric acid by inhibiting xanthine oxidase

30
Q

What are the common side effects of allopurinol? When should you NOT use it?

A

GI; dermatitis

not with patients who have liver disease or bone marrow depression

31
Q

What are the FDA approved NSAIDs to use with gout?

A

indomethacin
naproxen
sulindac

32
Q

T/F Corticosteroids are a frequently used & helpful treatment option for gout.

A

False. Usu not used.

33
Q

Febuxostate aka uloric is a treatment for gout. How does it work?

A

lowers uric acid levels

non-purine inhibitor of uric acid by forming a complex with an enzyme

34
Q

HOw is febuxostate aka uloric eliminated? WHat is its half life?

A

metabolized by CYP2C9
renal & hepatic elimination
t1/2=5-8 hrs

35
Q

When do you use febuxostate aka uloric? What are its potential side effects?

A

used for attacks, not for when patients are asymptomatic

liver toxicity & cardio problems are major side effects

36
Q

What is rasburicase aka elitek?

A

pediatric management of uric acid

usu for patients receiving chemo or experiencing tumor lysis syndrome–often experience hyperuricemia with cell turnover

37
Q

What is used to treat acute gout?

A
nonsalicylate NSAIDs (indomethacin, naproxne, sulindac)
sometimes colchicine for a few weeks
38
Q

What is used to treat chronic gout?

A
uricosuric agents (probenecid & sulfinpyrazone)
\+allopurinol
39
Q

What are maintenance drugs for patients with gout?

A

allopurinol, probenecid, sulfinpyrazone