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M&M Test 1 > B6-038 Gout & Hyperuricemia > Flashcards

B6-038 Gout & Hyperuricemia Flashcards

(84 cards)

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1
Q

the urate crystals present in tophi come from

A

purine breakdown

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2
Q

[….] is the only biochemical pathway that has urate as the end product

A

purine breakdown

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3
Q

the conversion of glutamine to glutamate is what type of reaction?

A

amidation

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4
Q

does amidation occur in purine or pyrimidine synthesis?

A

both :)

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5
Q

[…] provides the carbon backbones during the de novo synthesis of nucleotide bases

A

amino acids

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6
Q

synthesis of […] requires vitamin B9

A

purine bases

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7
Q

PRPP synthase is regulated by

A

purine and pyrimidine nucleotides (end product inhibition)

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8
Q

UTP inhibits […], which helps build the ring in pyrimidine synthesis

A

CAD complex

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9
Q

the first step of the salvage of purine bases is

A

addition of ribose

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10
Q

3 purine bases

A

hypoxanthine, adenine, guanine

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11
Q

loss of the enzyme HGPRT causes

A

Lesch-Nyhan syndrome

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12
Q

classic presentation: male child with motor symptoms, self-mutilation, gout

A

Lesch-Nyhan syndrome

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13
Q

Lesch-Nyhan syndrome is a defect in

A

purine salvage

causes excess de novo purine synthesis leading to excess uric acid

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14
Q

key enzyme in deoxynucleotide synthesis

A

ribonucleotide reductase

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15
Q

hydroxyurea and gemcitabine inhibit what enzyme?

A

ribonucleotide reductase

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16
Q

what enzyme is deficient in SCID?

A

adenosine deaminase

(involved in purine breakdown)

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17
Q

proper regulation of ribonucleotide reductase results in

A

the concentration of all four dNTPs in a cell being roughly equivalent

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18
Q

if dCTP is elevated, how might that effect ribonucleotide reductase?

A

dCTP would allosterically effect RNR resulting in increased production of ADP, UDP, and GDP

**always trying to ensure all four substrates are roughly equal in cell

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19
Q

primary hyperuricemia is caused by

A

in-born defects

**secondary is unrelated to genetics

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20
Q

in a patient with gout, prevalence of […] correlates with serum and urinary uric acid levels

A

nephrolithiasis

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21
Q

for the management of gout, the American College of Rheumatology recommends against

A

vitamin C supplementation

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22
Q

evidence of support for lifestyle/diet recommendations in the management of gout is [high or low]

A

low

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23
Q

standard of care diagnostic test for gout

A

synovial fluid aspirate

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24
Q

why do pre-menopausal females have lower serum uric acid levels than males?

A

estrogen impact activity of renal uric acid transporters

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25
what part of the renal tubule regulates uric acid?
PCT
26
inhibits xanthine oxidase, directly reducing the production of uric acid
allopurinol
27
inhibits OAT transporters
probenecid
28
inhibits URAT1 transporter
lesinurad
29
inhibits reabsorption of urate from urine [2]
probenecid, lesinurad
30
inhibits ribonucleotide reductase, preventing the synthesis of deoxyribonucleotides
hydroxyurea
31
promotes degradation of urate in serum
pegloticase
32
third line treatment for persistent gout, very expensive
pegloticase
33
inhibits tubulin polymerization, used to treat inflammatory conditions
colchicine
34
inhibits de novo pyrimidine base synthesis preventing cell division making it useful in the treatment of rheumatoid disease
leflunomide **not helpful for gout as it's for pyrimidine synthesis, not purine
35
hydroxyurea prevents
deoxyribonucleotide synthesis
36
allopurinol and febuxostat MOA
purine breakdown
37
key enzyme in purine breakdown inhibition of this reduces the production of uric acid
xanthine oxidase
38
is there strong evidence for managing gout with diet?
no **despite this, remains "gold standard". balance QOL with patient goals and evidence
39
crucial enzyme for synthesis of all nucleotides
PRPP synthetase **also involved in purine salvage pathway
40
inhibits dihydrofolate reductase
methotrexate
41
best treatment for acute nephrolithiasis caused by tumor lysis syndrome
pegloticase
42
how does an in-born error in G6P cause an elevated risk of hyperuricemia?
glucose-6-phosphate builds up in liver --> shunts into PPP --> produces more nucleotides --> catabolized --> high levels of uric acid
43
limited in use of treatment of gout due to impact on excretion of other drugs in kidney
probenecid
44
inhibits reabsorption of uric acid by URAT1 in PCT
lesinurad **no longer manufactured
45
recombinant PEGylated-urate oxidase converts urate to allantoin
pegloticase
46
drugs for gout that do NOT impact nucleotide metabolism [3]
pegloticase lesinurad (d/c) probenecid
47
inhibit xanthine oxidase to directly reduce uric acid production, specifically treating gout
allopurinol febuxostat
48
drugs that inhibit cell division by reducing nucleotide availability used to treat autoimmune disorder and cancer, not necessarily gout [3]
lefunomide (arthritis) hydroxyurea (cancer) methotrexate
49
transporters in PCT that may be responsible for association of gout and high fructose sodas
GLUT9
50
"priming" of uric acid reabsorption is dependent on [...] loading the PCT cells with anions
sodium
51
gout is defined as both [...] and [...]
crystal formation and inflammation
52
adenosine deaminase deficiency causes
SCID
53
how does adenosine deaminase deficiency cause SCID?
prevents adenosine breakdown --> adenosine builds up, inhibiting RNR --> reduces dNTP pool --> immune cells are very mitotically active so they are very sensitive to this
54
unbalanced dNTPs can lead to
ds breaks in DNA
55
ribonucletotide reductase inhibitors
hydroxyurea, gemcitabine
56
condition resulting from defective purine salvage
Lesch-Nyhan
57
can be given prophylactically to help prevent tumor lysis syndrome caused by chemotherapy
allopurinol
57
converts ribose to PRPP
PRPP synthetase
57
how does tumor lysis syndrome cause hyperuricemia?
high levels of nucleotide catabolism
58
gout is caused by the precipitation of [....] crystals in joints
monosodium urate
59
needle shaped crystals under polarized light
gout
60
treatment for ACUTE gout [3]
NSAIDs, glucocorticoids, colchicine
61
preventative treatment for chronic gout [2]
allopurinol febuxostat
62
allopurinol and febuxostat competitively inhibit
xanthine oxidase
63
allopurinol can be used concurrently with chemotherapy to prevent
tumor lysis associated urate nephropathy
64
allopurinol can increase the concentrations of [2]
azathioprine 6-MP
65
recombinant uricase catalyzing uric acid to allantion
pegloticase
66
inhibits reabsorption of uric acid in PCT
probenecid
67
probenecid can also inhibit the secretion of
penicillin
68
can precipitate uric acid calculi or lead to sulfa allergies
probenecid
69
binds and stabilizes tubulin to inhibit microtubule polymerization
colchicine
70
colchicine inhibits [....], causing impaired neutrophil [...] and [...]
microtubule polymerization chemotaxis degranulation
71
rate determining enzyme of the HMP shunt
G6PD
72
rate limiting enzyme of de novo purine synthesis
PRPP
73
inhibits ribonucleotide reductase
hydroxyurea
74
inhibits dihydrofolate reductase in humans
methotrexate
75
lesch-nyhan is caused by
defective purine salvage
76
one of the major causes of autosomal recessive SCID
adenosine deaminase deficiency
77
what enzyme is absent in Lesch-Nyhan?
HGPRT
78
key enzyme in the purine salvage pathway
HGPRT
79
which pathway operates at a higher rate in children with Lesch-Nyhan?
de novo purine synthesis
80
leflunomide inhibits [....] synthesis
pyrimidine
81
medication that inhibits dihydoorotate dehydrogenase
leflunomide
82
leflunoamide is used to treat
rheumatoid arthritis

M&M Test 1 (15 decks)

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