Lecture 8 - Gout Flashcards
hyper-uricemia is defined as serum urate > ___ mg/dl=L. above this concentration, uric acid exceeds ____
6.8;
solubility
Gout is more common in what gender?
men
_____ is painful MTP joint of big toe.
_____ are deposits of monosodium urate cartilage i.e. external ear, olcrenon bursa, ____ tendon
podagra;
tophi;
achilles
gout is more common in upper or lower joints?
due to ___ temperature here
lower;
low = increased precipitation
gout complications:
nephrolithiasis that precipitates at ___ pH. radio____ on X-ray. ____ shaped.
decreased;
radiolucent;
rhomboid shaped
gouty nephropathy:
acutely, due to ____ flow blockage by precipitation of crystals. see in paitents with what kind of cancer?
chronically, causes _____ in the urine and renal failure
urine;
leukemia;
protein
why does alcohol precipitate gout?
why does red meat?
ETOH = competes for same excretion sites, also increases purine catabolism and increases acidity of blood;
meat: has lots of purines in it
secondary gout occurs due to increased cell ____. hit me with an example
turnover/death
chemo, leukemias,
besides chemo, name another drug that can precipitate acute gout?
thiazide/loop diuretics;
also salicylates, L-dopa, cyclosprine,
uric acid is formed from metabolism of purines or pyrimidines?
what enzyme is involved in this metabolism?
purines;
xanthine oxidase
e.g. hypoxanthine –> xanthine –> uric acid
isonine is converted to hypozanthine by ______;
IMP is converted to hypoxanthine by _____
PRPP (purine nucleoside phosphorylase);
HGPRT (i’m not typing that out)
decreased HGPRT activity, such as in _____, results in excess uric acid production
Lesch-Nyan syndrome
monosodium urate deposition activates _____, which release inflammatory cytokines
PMNs
colchicine:
binds and stabilizes _____, inhibiting _____;
impairs PMN ____ and ____;
decreased _____ (a cytokine) formation
tubulin, polymerization;
degranulation, chemotaxis;
LTB4
colchicine:
most common side effect is _____;
can rarely cause ______
diarrhea (and other GI probs);
bone marrow suppression
colchicine is metabolized by ___ and ____
CYP3A4, P-glycoprotein;
interactions with protease inhibitors, azoles, anti-fungals, macrolides
besides colchicine, what other 2 drugs are used for acute gout?
which should you avoid tho
NSAIDS, corticosteroids
avoid aspirin
probenecid:
inhibits _____ of uric acid in the ______
reabsorption;
PCT
probenicid blocks urinary secretion of other drugs ie _____
penicillin
2 side effects of probenecid:
sulfa allergy, can precipitate calculi
why shouldn’t aspirin be used for acute gout?
can decrease uric acid excretion (compete at anionic transporter)
allopurinol is an isomer of _____. it _____ inhibits ______
hypoxanthine;
competitively inhibits xanthine oxidase
inhibits reduced form, not oxidized form
allopurinol:
causes increased concentrations of ____ and _____ by decreasing metabolism
6-MP, azathioprine
allopurinol side effects:
rash, ____ (derm thing);
_____ syndrome;
test for HLA-B5801 in ____ patients
SJS/TENS;d
DRESS;
chinese
allopurinol is used in leukemia and lymphoma to prevent ____
tumor lysis syndrome
febuxostat: ______ inhibitor of xanthine oxidase;
extensively metabolized in _____ so use in patients with ____ problems
non-purine (both reduced and oxidized form);
liver;
kidney
pegloticase:
is a recombinant ____ that catalyzes metabolism of uric acid to ____, which is more ____ soluble
uricase;
allantoin;
water
used IV for refractory gout
side effects of pegloticase
hemolysis if G6PD deficient;
anaphylaxis
rasburicase is a recombinant ______. given IV to prevent _____
uricase;
tumor lysis syndrome (leukemia patients)
