Gout Flashcards
Gout occurs when what accumulates in joint?
Uric acid
How does the body break down uric acid?
Dissolves in blood and passes through kidneys
Purines have a (single/double) ring structure
Double
Pyrimadines have a (single/double) ring structure
Single
Which nitrogenous bases are pyrimadines?
Cytosine, thymine, uracil
Uric acid forms when what breaks down?
Purines
What enzyme is required to breakdown xanthine into uric acid?
Xanthine oxidase
Uric acid is a (weak/strong) acid
Weak. Pka = 5.3
Which class of medications are first line for gout?
Xanthine oxidase inhibitors
Examples of xanthine oxidase inhibitors
Allopurinol, febuxostat
Which classes of medication are second line for gout?
.UA degradation
.Increase renal urate excretion
Which compound is an analogues of hypoxanthine and xanthine?
a. Febuxostat
b. Allopurinol
c. Benzbromarone
d. probenecid
b. Allopurinol
Which compound is NOT a XO inhibitor
a. Febuxostat
b. Allopurinol
c. Oxypurinol
d. Allantoin
d. Allantoin
True or false: Allopurinol is structurally similar to hypoxanthine and it competitively binds at xanthine receptors.
True
How many oxygen atoms in uric acid?
3
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
c. Inhibiting Uric acid oxidation
Which metal atom in the active site of xanthine oxidase?
Molybdenum
Uricosurics MOA
Increase renal urate excretion by inhibiting URAT1 and GLUT9 transporters
Examples of uricosurics
.Benzbromarone (pulled from market due to death from hepatic failure)
.Probenecid
Cautions with probenecid
Has many significant drug interactions (NSAIDs, beta-lactams, heparin, etc.)
List two important transporters for Uric acid reabsorption
URAT1 and GLUT9
Which part of kidney is important for uric acid reabsorption?
Proximal convoluted tubule
What is the function of Uricase (Pegloticase)?
Convert uric acid to allantoin via oxidation
Which form, uric acid or urate, is predominant at pH 7.4?
Urate
Hyperuricemia Hyperuricemia is defined as uric acid levels above:
7 mg/dL for men
6 mg/dL women
True or false: Hyperuricemia always causes gout
False. Hyperuricemia can be asymptomatic
Medications that alter urate balance
. Diuretics
. Ethanol
. Salicylates
. Nicotinic acid
. Pyrazinamide
. Cyclosporin
Signs/symptoms of gout
.Intense pain
.Erythema
.Warmth
.Fever
.Tophi
.Inflammation of joint: toes, knees, fingers, elbows, ankles
Possible causes of gout flare
.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
Chronic tophaceous gouty arthropathy (CTGA) severity
.Mild: 1 joint, stable
.Moderate: 2-4 joints, stable
.Severe: 4 or more joints or unstable, complicated, tophi present)
Non-pharmacological modifications for gout
- 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
Which NSAIDs are FDA approved for acute gout treatment?
.Sulindac
.Indomethacin
.Naproxen
True or false: Selective COX-2 inhibitors should be avoided in significant CAD history
True. Associated with increased risk of CV events
Contraindications for NSAIDs
.Decompensated HF
.CrCL less than or equal to 30mL/min
True or false: Corticosteroids may be administered when the patient has an active systemic infection
False. Corticosteroids are immunosuppressive
Colchicine dosing
Initial - Day 1: 1.2mg PO once. Day 2: After 12hrs
Maintenance: 0.6mg po 1hr later. 0.6mg PO qd or bid
When should colchicine be initiated?
.12-36 hours after onset of symptoms
.36+ hrs: consider alternative therapy
Colchicine contraindications
.Hepatic failure
.CrCl of 10mL/min or less
.Severe cardiac/GI disease
.Blood dyscrasias
Urate level goal
< 6mg/dL
True or false: ULT may be initiated during an acute flare
Yes, as long as overlapping prophylaxis is also initiated. And it is not the patient’s first flare
ULT is recommended when?
.Tophi
.2 or more gout flares a year
True or false: BID dosing of colchicine is more effective
False. BID dosing has same efficacy, but more side effects
How long should treatment be with tophi present?
6-12 months
How long should treatment be without tophi present?
3-6 months
Testing for which allele prior to initiating allopurinol is recommended for those of Southeast Asian descent and African American
HLA-B*5801
True or false: Uricosurics are often initiated as monotherapy
False. Rarely used monotherapy, however can if XOI is contraindicated or ineffective
Uricosuric contraindications
.Moderate-severe renal impairment (don’t use in stage 3 or worse CKD)
.Salicylates may impact probenecid concentrations
Pegloticase, a recombinant uricase from a modified strain of E. coli, should be initiated as (monotherapy/ adjunct therapy)
Monotherapy ONLY, not with other ULT therapy
When to d/c pegloticase
Serum urate still over 6 after first administration
Alternative gout therapies
.Fenofibrate - increase hypoxanthine and xanthine clearance
.Losartan - inhibits tubular resorption of uric acid/increases excretion
