Lecture 8 - Gout

Question 1

hyper-uricemia is defined as serum urate > ___ mg/dl=L. above this concentration, uric acid exceeds ____

Answer 1

6.8;

solubility

Question 2

Gout is more common in what gender?

Answer 2

men

Question 3

_____ is painful MTP joint of big toe.

_____ are deposits of monosodium urate cartilage i.e. external ear, olcrenon bursa, ____ tendon

Answer 3

podagra;
tophi;
achilles

Question 4

gout is more common in upper or lower joints?

due to ___ temperature here

Answer 4

lower;

low = increased precipitation

Question 5

gout complications:

nephrolithiasis that precipitates at ___ pH. radio____ on X-ray. ____ shaped.

Answer 5

decreased;
radiolucent;
rhomboid shaped

Question 6

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

Answer 6

urine;
leukemia;

protein

Question 7

why does alcohol precipitate gout?

why does red meat?

Answer 7

ETOH = competes for same excretion sites, also increases purine catabolism and increases acidity of blood;

meat: has lots of purines in it

Question 8

secondary gout occurs due to increased cell ____. hit me with an example

Answer 8

turnover/death

chemo, leukemias,

Question 9

besides chemo, name another drug that can precipitate acute gout?

Answer 9

thiazide/loop diuretics;

also salicylates, L-dopa, cyclosprine,

Question 10

uric acid is formed from metabolism of purines or pyrimidines?

what enzyme is involved in this metabolism?

Answer 10

purines;
xanthine oxidase

e.g. hypoxanthine –> xanthine –> uric acid

Question 11

isonine is converted to hypozanthine by ______;

IMP is converted to hypoxanthine by _____

Answer 11

PRPP (purine nucleoside phosphorylase);

HGPRT (i’m not typing that out)

Question 12

decreased HGPRT activity, such as in _____, results in excess uric acid production

Answer 12

Lesch-Nyan syndrome

Question 13

monosodium urate deposition activates _____, which release inflammatory cytokines

Answer 13

PMNs

Question 14

colchicine:
binds and stabilizes _____, inhibiting _____;
impairs PMN ____ and ____;
decreased _____ (a cytokine) formation

Answer 14

tubulin, polymerization;
degranulation, chemotaxis;
LTB4

Question 15

colchicine:
most common side effect is _____;
can rarely cause ______

Answer 15

diarrhea (and other GI probs);

bone marrow suppression

Question 16

colchicine is metabolized by ___ and ____

Answer 16

CYP3A4, P-glycoprotein;

interactions with protease inhibitors, azoles, anti-fungals, macrolides

Question 17

besides colchicine, what other 2 drugs are used for acute gout?

which should you avoid tho

Answer 17

NSAIDS, corticosteroids

avoid aspirin

Question 18

probenecid:

inhibits _____ of uric acid in the ______

Answer 18

reabsorption;

PCT

Question 19

probenicid blocks urinary secretion of other drugs ie _____

Answer 19

penicillin

Question 20

2 side effects of probenecid:

Answer 20

sulfa allergy, can precipitate calculi

Question 21

why shouldn’t aspirin be used for acute gout?

Answer 21

can decrease uric acid excretion (compete at anionic transporter)

Question 22

allopurinol is an isomer of _____. it _____ inhibits ______

Answer 22

hypoxanthine;
competitively inhibits xanthine oxidase

inhibits reduced form, not oxidized form

Question 23

allopurinol:

causes increased concentrations of ____ and _____ by decreasing metabolism

Answer 23

6-MP, azathioprine

Question 24

allopurinol side effects:
rash, ____ (derm thing);
_____ syndrome;
test for HLA-B5801 in ____ patients

Answer 24

SJS/TENS;d
DRESS;
chinese

Question 25

allopurinol is used in leukemia and lymphoma to prevent ____

Answer 25

tumor lysis syndrome

Question 26

febuxostat: ______ inhibitor of xanthine oxidase;

extensively metabolized in _____ so use in patients with ____ problems

Answer 26

non-purine (both reduced and oxidized form);
liver;
kidney

Question 27

pegloticase:

is a recombinant ____ that catalyzes metabolism of uric acid to ____, which is more ____ soluble

Answer 27

uricase;
allantoin;
water

used IV for refractory gout

Question 28

side effects of pegloticase

Answer 28

hemolysis if G6PD deficient;

anaphylaxis

Question 29

rasburicase is a recombinant ______. given IV to prevent _____

Answer 29

uricase;

tumor lysis syndrome (leukemia patients)