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Flashcards in Gout Deck (57)
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1
Q

T/F: All individuals with hyperuricemia will at some point develop a clinical event from urate crystal deposition

A

FALSE

Most individuals w/ hyperuricemia may never develop a clinical event from urate crystal deposition

(so don’t tx hyperuricemia if no h/o gout!)

2
Q

Drugs active in gout inhibit what 2 things?

A
  1. Crystal phagocytosis
  2. PMN and macrophage release of inflammatory mediators
3
Q

Is it more common for a person to have overproduction or underexcretion of uric acid?

A

Underexcretion

4
Q

Where is 2/3 of the daily uric acid production excreted?

A

In the urine

5
Q

2/3 of the daily uric acid production is excreted in the urine, where is the remainder eliminated?

A

Through the GI tract after enzymatic degradation by colonic bacteria

6
Q

The following are examples of _____ rich foods:

  • Bacon
  • Beef
  • Chicken
  • Mushrooms
  • etc
A

Purine rich foods

7
Q

What is the definitive dx of gout?

A

tapping the joint and microscopic exam of uric acid crystals

8
Q

In the absence of a history of gout, does asymptomatic hyperuricemia require treatment?

A

no

9
Q

What is acute gout?

A

Attacks of joint inflammation

3-10 days

Usually affecting the 1st MTP

10
Q

Which toe does acute gout most commonly affect?

(how many days, area MCly affected?)

A

1st MTP- Podagra “foot pain”

11
Q

Chronic or acute gout?

  • Rheumatoid-like
  • Tophaceous Gout
A

Chronic gout

12
Q

What type of urate is in the soft tissues and joints in Tophaceous gout?

A

Monosodium urate

13
Q

What is non-pharmacological treatment for acute gout?

A

Local ice application

(most effective as adjunctive tx)

14
Q

What are the 3 acute gout first line treatments?

A
  1. NSAIDs (Indomethacin, naproxen and Sulindac)
  2. Corticosteroids
  3. Colchicine
15
Q

Within how many hours of acute gout attack onset should treatment (NSAIDs, colchicine, steroids) be taken and for how many days?

(red)

A

Within 24 hours

until complete resolution, ~5-8 days after initiating therapy

16
Q

Mechanism of which acute gout med?

  • Inhibition of microtubule assembly decreases macrophage migration and phagocytosis
  • Inhibits leukotriene B4 decreasing inflammation
A

Colchicine

17
Q

Acute Gout tx:

Colchicine must be used w/in ___ hrs of attack onset to be effective

(red)

A

36

18
Q

What are the 3 ADEs of Colchicine?

(red)

A
  1. N/V/D
  2. Myelosuppression (rare)
  3. Neuromyopathy (reversible)
19
Q

Dose adjustment of Colchicine is recommended when used with what 2 groups of meds?

(red)

A

selected CYP3A4 and P-glycoprotein inhibitors

(so don’t give w/ -azoles or -vir)

20
Q

Colchicine inhibits renal tubular secretion of what med?

A

Methotrexate

21
Q

When is intraarticular corticosteorid (TAC-Kenalog) administration acceptable in the tx of acute gout?

What meds should it be used in combo with?

A
  • When only 1 or 2 joints involved
  • Should be used in combo w/ NSAIDs, Colchicine or oral corticosteroids
22
Q

What 3 meds can be used for tx of chronic gout?

A
  • Colchicine
  • Probenicid
  • Allopurinol, Febuxostat
23
Q

Which med should be used for refractory cases of chronic gout?

A

Pegloticase (Biologic)

24
Q

What are the 2 xanthine oxidase inhibitors used to tx chronic gout?

A

Allopurinol

Febuxostat

25
Q

Which chronic gout med currently only has an indication for hyperuricemia in malignancy

A

Rasburicase

26
Q

What is the main side effect of Colchicine and is often difficult to tolerate?

A

Dose dependent diarrhea

27
Q

What are the 3 anti-inflammatory regimens that are needed during the initiation of urate-lowering therapy (ULT)?

A
  1. Colchicine

OR

  1. Low dose NSAIDs w/ PPI

OR

  1. Prednisone
28
Q

Anti-inflammatory regimens (Colchicine, NSAIDs w/ PPI or prednisone) are required during the initiation of urate lowering therapy.

How long should they be continued?

A

Continue at least 6 months

or

3-6 months after achieving target serum uric acid

29
Q

What are Xanthine osidase inhibitors (allopurinol/febuxostat) efficacious for?

A

prophylaxis of recurrent gout attacks in both underexcreters and overproducers of uric acid

(red)

30
Q

In what 4 for initiation of allopurinol or febuxostat?

A
  • 2+ gout attacks per year
  • presence of 1+ tophus
  • CKD (stage 2 or worse)
  • history of urolithiasis
31
Q

What is the goal serum urate concentration level?

A

< 6mg/dL

or < 5 if signs of gout persist

32
Q

What is the first line Urate Lowering Therapy?

(red)

A

Xanthine Oxidase Inhibitor (Allopurinol)

33
Q

MOA of which chronic gout med?

  • Active metabolite irreversibly inhibits xanthine oxidase and lowers production of uric acid
A

Allopurinol

(Xanthine Oxidase Inhibitor)

34
Q

When prescribing Allopurinol, what do you need to educate patients about?

(red)

A

Acute Hypersensitivity syndrome

(highest risk in first few months of therapy)

35
Q

ADEs of which med?

  • Pruritis
  • rash
  • Elevated LFTs
  • Acute Hypersensitivey Syndrome
A

Allopurinol

36
Q

Which 2 high risk populations should you consider genetic testing for due to increased concern for Acute Hypersensitivity Syndrome while taking Allopurinol?

(red)

A
  • •Koreans with CKD
  • •Han Chinese and Thai irrespective of renal function
37
Q

Which Xanthine Oxidase Inhibitor is a reversible inhibitor of xanthine but is very expensive?

A

Febuxostat

38
Q

Febuxostat is contraindicated with what?

A

azathioprine

39
Q

Febuxostat:

  • •No dose adjustments in patients with mild to moderate _____ or ____ impairment
    *
A

Renal or hepatic

40
Q

What are the 4 ADEs of Febuxostat?

A

–Liver enzyme elevation

–Nausea

–Arthralgias

–Rash

41
Q

What are 2 things that you must monitor in a patient taking Febuxostat due to concern for toxicity?

A
  • Liver Function tests
  • Renal function
42
Q

T/F: Fubuxostat Can be used in both urate overproduction and urate under excretion

A

true

43
Q

Febuxostat:

  • No dosage adjustment necessary for patients with _______renal dysfunction (creatinine clearance ____–____ mL/min)
A

Mild to moderate

30-89

44
Q

What are the 2 Uricosouric Therapy options (increase uric acid excretion)?

A
  1. Probenecid
  2. XOI + fenofibrate or losartan
45
Q

For Probenecid, copious amounts of what is needed?

A

copious water consumption

46
Q

What are the 2 instances Probenecid should not be used?

A
  1. CC < 50mL/min
  2. h/o urolithiasis
47
Q

What does the following Uricosouric Therapy do:

XOI + fenofibrate or losartan

A

Augments uric acid excretion

48
Q

Which patients is the following Uricosouric Therapy beneficial for:

XOI + fenofibrate or losartan

A

Patients with other disorders

49
Q

Which med is used for patients refractory to conventional therapies?

A

Pegloticase

(Biologic)

50
Q

Which med should you consider prescribing in a patient with heavy disease burder w/ chronic tophaceous disease?

A

Pegloticase

(Biologic)

51
Q

MOA of which med?

  • Recombinant porcine-like uricase which then metabolizes uric acid to allantoin
  • Lowers uric acid levels and reduces deposits of uric acid crystals
A

Pegloticase

(Biologic)

52
Q

MOA of which med?

  • Inhibits function of transporter proteins involved in renal uric acid reabsorption (uric acid transporter 1-URAT1) and organic anion transporter 4 (OAT4)
  • Lowers serum uric acid levels and increases renal clearance and fractional excretion of uric acid
A

Lesinurad

53
Q

Which med is reserved for patients with hyperuricemia a/w gout who do not achieve target serum uric acid levels with conventional therapies?

(can be used in both overproducers or underproducers)

A

Lesinurad

54
Q

Lesinurad must be used in combo w/ a ______ due to increased risk of ________ with monotherapy

(know!)

A

Lesinurad must be used in combo w/ a Xanthine Oxidase Inhibitor (like Allopurinol) due to increased risk of Renal Failure with monotherapy

55
Q

ADEs of which med?

  • Acute gout attack during treatment initiation
  • Headache
  • GERD
  • Major adverse cardiovascular observed - causal relationship has not been established
  • Renal function toxicity
A

Lesinurad

56
Q

The following are off-labeled options, which are ______ inhibitors:

  • Anakinra
  • Canakinumab
  • Rilonacept
A

Interleukin-1 inhibitors

57
Q

Do you initiate monotherapy or combo therapy if a patient is complaining of severe pain during an acute gout attack?

A

Use combo therapy (ex: colchicine + NSAID)

(mild-moderate pain you could use monotherapy)