Gout

Question 1

Gout occurs when what accumulates in joint?

Answer 1

Uric acid

Question 2

How does the body break down uric acid?

Answer 2

Dissolves in blood and passes through kidneys

Question 3

Purines have a (single/double) ring structure

Answer 3

Double

Question 4

Pyrimadines have a (single/double) ring structure

Answer 4

Single

Question 5

Which nitrogenous bases are pyrimadines?

Answer 5

Cytosine, thymine, uracil

Question 6

Uric acid forms when what breaks down?

Answer 6

Purines

Question 7

What enzyme is required to breakdown xanthine into uric acid?

Answer 7

Xanthine oxidase

Question 8

Uric acid is a (weak/strong) acid

Answer 8

Weak. Pka = 5.3

Question 9

Which class of medications are first line for gout?

Answer 9

Xanthine oxidase inhibitors

Question 10

Examples of xanthine oxidase inhibitors

Answer 10

Allopurinol, febuxostat

Question 11

Which classes of medication are second line for gout?

Answer 11

.UA degradation
.Increase renal urate excretion

Question 12

Which compound is an analogues of hypoxanthine and xanthine?
a. Febuxostat
b. Allopurinol
c. Benzbromarone
d. probenecid

Answer 12

b. Allopurinol

Question 13

Which compound is NOT a XO inhibitor
a. Febuxostat
b. Allopurinol
c. Oxypurinol
d. Allantoin

Answer 13

d. Allantoin

Question 14

True or false: Allopurinol is structurally similar to hypoxanthine and it competitively binds at xanthine receptors.

Answer 14

True

Question 15

How many oxygen atoms in uric acid?

Answer 15

3

Question 16

Which way is NOT good for the treatment of hyperuricemia?
a. Inhibiting Xanthine Oxidation
b. Inhibiting Uric acid reabsorption
c. Inhibiting Uric acid oxidation
d. Converting Uric acid to Allantoin

Answer 16

c. Inhibiting Uric acid oxidation

Question 17

Which metal atom in the active site of xanthine oxidase?

Answer 17

Molybdenum

Question 18

Uricosurics MOA

Answer 18

Increase renal urate excretion by inhibiting URAT1 and GLUT9 transporters

Question 19

Examples of uricosurics

Answer 19

.Benzbromarone (pulled from market due to death from hepatic failure)
.Probenecid

Question 20

Cautions with probenecid

Answer 20

Has many significant drug interactions (NSAIDs, beta-lactams, heparin, etc.)

Question 21

List two important transporters for Uric acid reabsorption

Answer 21

URAT1 and GLUT9

Question 22

Which part of kidney is important for uric acid reabsorption?

Answer 22

Proximal convoluted tubule

Question 23

What is the function of Uricase (Pegloticase)?

Answer 23

Convert uric acid to allantoin via oxidation

Question 24

Which form, uric acid or urate, is predominant at pH 7.4?

Answer 24

Urate

Question 25

Hyperuricemia Hyperuricemia is defined as uric acid levels above:

Answer 25

7 mg/dL for men 6 mg/dL women

Question 26

True or false: Hyperuricemia always causes gout

Answer 26

False. Hyperuricemia can be asymptomatic

Question 27

Medications that alter urate balance

Answer 27

. Diuretics . Ethanol . Salicylates . Nicotinic acid . Pyrazinamide . Cyclosporin

Question 28

Signs/symptoms of gout

Answer 28

.Intense pain .Erythema .Warmth .Fever .Tophi .Inflammation of joint: toes, knees, fingers, elbows, ankles

Question 29

Possible causes of gout flare

Answer 29

.Dehydration .Stress .Excessive alcohol intake .Excessive intake of purine rich foods .Increased physical activity .Use of uric acid lowering agents .Use of medications that increase uric acid levels

Question 30

Chronic tophaceous gouty arthropathy (CTGA) severity

Answer 30

.Mild: 1 joint, stable .Moderate: 2-4 joints, stable .Severe: 4 or more joints or unstable, complicated, tophi present)

Question 31

Non-pharmacological modifications for gout

Answer 31

* Limit purine rich foods (meats, seafood) * Limit alcohol intake (i.e. beer, fortified wines/liquors) * Limit high-fructose corn syrup * Maintain adequate hydration * Weight loss * Ice therapy

Question 32

Which NSAIDs are FDA approved for acute gout treatment?

Answer 32

.Sulindac .Indomethacin .Naproxen

Question 33

True or false: Selective COX-2 inhibitors should be avoided in significant CAD history

Answer 33

True. Associated with increased risk of CV events

Question 34

Contraindications for NSAIDs

Answer 34

.Decompensated HF .CrCL less than or equal to 30mL/min

Question 35

True or false: Corticosteroids may be administered when the patient has an active systemic infection

Answer 35

False. Corticosteroids are immunosuppressive

Question 36

Colchicine dosing

Answer 36

Initial - Day 1: 1.2mg PO once. Day 2: After 12hrs Maintenance: 0.6mg po 1hr later. 0.6mg PO qd or bid

Question 37

When should colchicine be initiated?

Answer 37

.12-36 hours after onset of symptoms .36+ hrs: consider alternative therapy

Question 38

Colchicine contraindications

Answer 38

.Hepatic failure .CrCl of 10mL/min or less .Severe cardiac/GI disease .Blood dyscrasias

Question 39

Urate level goal

Answer 39

< 6mg/dL

Question 40

True or false: ULT may be initiated during an acute flare

Answer 40

Yes, as long as overlapping prophylaxis is also initiated. And it is not the patient's first flare

Question 41

ULT is recommended when?

Answer 41

.Tophi .2 or more gout flares a year

Question 42

True or false: BID dosing of colchicine is more effective

Answer 42

False. BID dosing has same efficacy, but more side effects

Question 43

How long should treatment be with tophi present?

Answer 43

6-12 months

Question 44

How long should treatment be without tophi present?

Answer 44

3-6 months

Question 45

Testing for which allele prior to initiating allopurinol is recommended for those of Southeast Asian descent and African American

Answer 45

HLA-B*5801

Question 46

True or false: Uricosurics are often initiated as monotherapy

Answer 46

False. Rarely used monotherapy, however can if XOI is contraindicated or ineffective

Question 47

Uricosuric contraindications

Answer 47

.Moderate-severe renal impairment (don't use in stage 3 or worse CKD) .Salicylates may impact probenecid concentrations

Question 48

Pegloticase, a recombinant uricase from a modified strain of E. coli, should be initiated as (monotherapy/ adjunct therapy)

Answer 48

Monotherapy ONLY, not with other ULT therapy

Question 49

When to d/c pegloticase

Answer 49

Serum urate still over 6 after first administration

Question 50

Alternative gout therapies

Answer 50

.Fenofibrate - increase hypoxanthine and xanthine clearance .Losartan - inhibits tubular resorption of uric acid/increases excretion