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Musculoskeletal 2 > Pharm - Gout > Flashcards

Pharm - Gout Flashcards

1
Q

Defne hyperuricemia

A
  • not gout but increases risk for gout
  • necessary for development of urate crystal deposition
  • elevated uric acid in the blood
  • uric acid level > 6 mg/dL
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2
Q

Define Gout

A
  • Arthritic condition resulting from deposition of monosodium urate (MSU) crystals in and/or around joints, bones, soft tissues following long-standing hyperuricemia
  • A clinical syndrome
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3
Q

Define Tophus/tophi

A
  • pathognomonic feature of gout

* Deposit of crystalline uric acid and other substances at surface of joint or in skin or cartilage

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4
Q

What food and drink should be avoided/limited to prevent gout

A

Avoid:
- BEER, alcohol overuse (>2/day men, >1/day women
- organ meets high in purines,
- high fructose corn syrup (soda, beverage, food)
Limit:
- beef, lamb, pork, seafood with high purine (sardines, shellfish)
- naturally sweetened fruit juice
- table sugar
- salt

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5
Q

What is goal of therapy when treating acute gout attack

A

Prompt and safe termination of pain and disability

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6
Q

What is the timeline for treating an acute gout attack

A
  • Sudden in onset, severe debilitating pain with max intensity within 8-12 hrs
  • Initiate treatment as soon as possible, preferably within several hours of sx onset
  • Continue tx for duration of attack
  • Continue tx until the pt has been sx free for 2-3 days
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7
Q

What factors should modify the selection of anti-inflammatory drug for acute gout attack tx

A
  • Renal function
  • CVD (HF and poorly controlled HTN)
  • GI disease, including peptic ulcer disease
  • Drug allergy
  • Poorly controlled DM
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8
Q

Indications for us of glucocorticoid in the tx of acute gout attack

A

Mild to moderate pain, attack only affects one or a few small joints or 1-2 lrg joints

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9
Q

what is the amount of intra-articular glucocorticoid in the treat of acute gout attack based on?

A

The size of the joint

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10
Q

What can occur when oral glucocorticoid tx is withdrawn?

A

rebound gout attack

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11
Q

What is the role of NSAID in the tx of acute gout attack?

A
  • Mild to moderate pain, attack only affects one or a few small joints or 1-2 lrg joints
  • Good alternative to glucocorticoids esp if <60, no renal dz, no CVD, no active GI dz
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12
Q

Who should NOT receive NSAIDs for tx of acute gout attack (7)

A
  • Hx of peptic ulcer dz (duodenal or gastric)
  • Hx of GI bleeding
  • Predisposed to gastritis
  • Renal insufficiency (CrCl <60)
  • Abnl heaptic fn
  • Use anticoagulants
  • Limit in elderly due to CNS effects
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13
Q

Duration of NSAID when tx acute gout attack

A
  • Start within 12-24 hours of attack beginning
  • Start at highest dose for 2-3 days, then decrease over approx. 2 weeks
  • Continue for at least 48 hours after resolution of sx
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14
Q

Role of colchicine in tx of acute gout

A
  • If pt has contraindication to NSAIDs (mod-severe chronic kidney dz, active peptic ulcer disease, or hx of NSAID intolerance)
  • May abort attacks of gout if used as soon as pt perceives the first sign of an attack.
  • May be an alternative to glucocorticoids or NSAIDs for flare tx if it has worked in past
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15
Q

What are the contraindications to colchicine

A

Concomitant use of a strong CYP3A4 inhibitor or a P-glycoprotein inhibitor if pt has renal or liver impairment

**Amiodarone, PPI, SSRI, CaCB, macrolides)

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16
Q

What is the dosing regimen for the treatment of colchicine for an acute gout attack

A

Day 1:
• 1.2 mg at first sign of flare, 1 hour later a single dose of 0.6 mg (max 1.8 within one hour) OR
• 0.6 mg TID on first day of flare (max total dose 1.8 mg on day 1)
• If already receiving prophylactic colchicine, resume prophylaxis dosing 12 hours after initial treatment (results in higher doses being administrated on day 1)

Day 2:
• 0.6 mg once or twice daily until flare resolves

17
Q

What are the indications for uric acid lowering therapy (6)

A
  • Tophaceous deposits in soft tissue or subchondral bone (IDed via clinical exam or imaging)
  • Clinical or radiographic signs of chronic gouty joint disease (gouty arthropathy)
  • Frequent gout attacks of acute gout arthritis (≥2 attacks/yr)
  • Chronic kidney disease stage 2 or worse (CrCl <60 mL/min)
  • Hx of uric acid renal stones
  • Urinary uric acid excretion exceeding 1100 mg/day in men <25 or premenopausal woman (increased risk of uric acid stones)
18
Q

What is the uric acid treatment target when using uric acid lowering tx?

A

< 6 ml/dL

19
Q

What are the drugs of choice for the prevention of gout

A

1st line: Xanthine Oxidase inhibitor (XOI)
• Allopurinol (cheaper)
• Febuxostat (Uloric)
Second Line (XOI is contra-indicated or not tolerated)
• Probenecid (Benemid)
• Lesinurad (Zurampic)
• Alternative uricosuric agents

20
Q

What is the risk for an acute gout attack when initiating uric acid lowering therapy

A
  • Tx acutely lowers uric acid in blood, mobilizing urate cyrstals from body tissues and joints, precipitating a gout attack!
  • Wait two weeks min after acute attack to start uric acid lowering therapy may reduce risk
21
Q

What is the role of colchicine in acute gout prophylaxis

A

1st line for acute gout attack prophylaxis (0.6 mg once or twice daily)
• Note: 1st line prophylaxis is colchicine OR NSAID with PPI

22
Q

What is MoA of colchicine

A
  • anti-inflammatory.
  • Reduces inflammatory response to deposited cyrstals by diminishing the ability of white blood cells to phagocytize crystals and blocks cellular response to deposited crystals.
  • Inhibits polymerization of tubulin in microtubules, preventing ability of cell to move in body. Why have to initiate treatment early, before WBC reach the site of inflammation.
23
Q

What is the duration of tx for acute gout prophylaxis when starting uric acid lowering agent?

A
  • Continue if gout signs and sx persist
  • If no signs or sx of gout:
    • Continue for min 6 months OR
    • Treat for 3 months after achieving target serum urate and no tophi detected on PE
    • Treat for 6 months after achieving target serum urate if 1+ tophi detected on PE
24
Q

What are the two xanthine oxidase inhibitors

A
  • Allopurinol

- febuxostat

25
Q

What is the MoA of xanthine oxidase inhibitors

A

prevents the conversion of hypoxanthine to uric acid

26
Q

What is the starting dose of allopurinol in pts with adequate renal function?

A

100 mg/day

27
Q

What patients are at highest risk for hypersensitivity to allopurinol?

A
  • Han Chinese, Thai, Korean heritage who have a CrCl <60 mL/min
28
Q

What testing is required for pts at high risk for allopurinol hypersensitivity?

A

HLA testing: HLA-B 5801

29
Q

What are the three uricoseric agents?

A
  • probenecid
  • Lesinurad
  • pegloticase
30
Q

What is the uricoseric MoA of Probenecid and lesinurad

A

Increases renal excretion of uric acid by inhibiting anionic transport sites (URAT transporters) in the renal PCT

*Lesinurad also OAT4

31
Q

Best candidate for probenecid therapy

A
  • Younger, <60 yo
  • Underexcreter of uric acid
  • Good renal function CrCl > 60 mL/min
  • No hx of kidney stones
  • Do not require aspirin or diuretic therapy
32
Q

Contraindications for probenecid therapy

A
  • History of urolithiasis
  • Indications of uric acid overproduction
  • Renal fn <60 mL/min
  • Might need high dose ASA or diuretic therapy
33
Q

What is the major drug interaction with probenecid?

A

high dose ASA antagonizes the action of probenecid

34
Q

What is the place in therapy for lesinurad

A

In combo with XOI in pts who have not achieved target serum uric acid levels with XOI alone

35
Q

What gout drug should never be used as mono therapy?

A

Lesinurad

36
Q

What is the MoA for pegloticase

A
  • Modified version of uricase, an enzyme that catalyzes the oxidation of uric acid to allantoin which is water soluble and easily eliminated
  • Lowers serum uric acid level to improve or reverse the course of severe, crippling gout
37
Q

What is the major contraindication associated with pegloticase

A

Pts with G6PD deficiency

- Use by these pts = increased risk of hemolysis and methemoglobinemia

38
Q

What are the two major ADR of colchicine

A
  • diarrhea

- abd cramps

Musculoskeletal 2 (14 decks)

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