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Gout Flashcards

1
Q

What is gout and its cause?

A
  • Gout is a type of arthritis caused by a buildup of uric acid (UA) crystals, primarily in the joints
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2
Q

How is UA produced?

A
  • UA is produced as an end-product of purine metabolism
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3
Q

T/F: Purines are present in many foods, and they make up one of the base pairs of DNA

A
  • True
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4
Q

When UA builds up in the blood, the patient can remain __ or the UA can __ in the joints, resulting in a __ gout attack

Fill in the blanks

A
  • Asymptomatic
  • Crystallize
  • Painful
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5
Q

What are the characteristics of a gout attack?

A
  • Sudden onset
  • Typically in one joint
  • Most often in metatarsophalangeal joint (MTP, the big toe)
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6
Q

What is used to identify UA crystals in the body?

A
  • A sample of synovial (joint) fluid
  • Evaluating UA level in the body
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7
Q

What are the risk factors for gout?

A
  • Male sex
  • Obesity
  • Excessive alcohol consumption
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8
Q

List drugs that increase UA

A
  • Aspirin, lower doses
  • Calcineurin inhibitors (tacrolimus and cyclosporin)
  • Diuretics (loops and thiazides)
  • Niacin
  • Pyrazinamide
  • Select chemotherapy (with tumor lysis syndrome)
  • Select pancratic enzyme products
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9
Q

T/F: Asymptomatic hyperuricemia is not treated with drugs

A
  • True
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10
Q

The drugs used for acute attacks target __ and __.

Fill in the blanks

A
  • Pain
  • Inflammation
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11
Q

Why prophylactic drugs are used?

A
  • Used to lower UA levels with a goal UA level of < 6 mg/dL
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12
Q

Which anti-inflammatory drugs are used to treat acute pain?

A
  • Colchicine
  • Steroids (including intra-articular injections)
  • NSAIDs (often with a high starting dose)
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13
Q

Once gout has struck, which medications are used to chronically treat to prevent future attacks?

A

Xanthine oxidase inhibitor (XOI):
* Allopurinol (preferred)

  • Febuxostat
  • An acute gout flare can occur when an XOI is started, so give initially with colchicine or an NSAID

If XOI didn’t work well and UA remains >6 mg/dL:
* Add on probenecid or lesinurad to daily XOI

  • Replace the XOI with IV pegloticase (Krystexxa)
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14
Q

How do you initially treat acute gout attack?

A
  • It should be treated with a single drug, either an NSAID, a systemic steroid or colchicine
  • If severe, combination treatment should be initiated. Thiis included colchicine with either an NSAID or an oral steroid
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15
Q

What can be helpful if the gout attack is localized to one or two joints?

A
  • An intra-articular steroid injection which is injected into joint/s
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16
Q

T/F: The ULT treatment should be continued if an acute attack occurs in a patient using ULT

ULT: allopurinol, febuxostat

17
Q

Colchicine - brand/generic, dosing, CIs, warnings, SEs

A

Colchicine (Colcrys)

Dosing (Treatment):
* Start within 36 hours of symptom onset

  • Wait 12 hours after a treatment dose before resuming prophylaxis dosing
  • 1.2 mg PO followed by 0.6 mg in 1hr
  • Do not exceed a total of 1.8 mg in 1 hr or 2.4 mg/day

Contraindications:
* Do not use in combination with a P-gp or strong CYP3A4 inhibitor with renal and/or hepatic impairment

Warnings:
* Myelosuppression

  • ↑ myopathy risk

Side effects:
* Diarrhea, nausea, myopathy, neuropathy

18
Q

NSAIDs - medications

A
  • Indomethacin (Indocin)
  • Naproxen (Aleve)
  • Celecoxib (Celebrex)
19
Q

Avoid use of NSAIDs in severe __ disease and __ risk.

Fill in the blanks

20
Q

Steroids - formulations, SEs

A

Formulations:
* Steroids are given PO, IM, IV, intra-articular or as ACTH (adrenocorticotropic hormone), which triggers endogenous glucocorticoid secretion

SEs:
* ↑BG,↑BP, ↑ appetite, insomnia

21
Q

Steroids: medications

A
  • Prednisone/Prednisolone
  • Methylprednisolone (Medrol, Solu-Medrol)
22
Q

T/F: Methylprednisolone should be initiated intra-articularly if 1-2 large joints involved

23
List colchicine DIs
Fatal toxicity: CYP3A4 inhibitors or strong P-gp inhibitors
24
What is the first-line prophylactic treatment for gout?
**Chronic ULT** * Initiate if one or more gout attacks are experienced or joint damage or tophi has occured * Allopurinol, xanthine oxidase inhibitor (XOI) is the first line drug * XOI stops the production of UA and it should be titrated up slowly to lower UA level of <6 mg/dL * High risk of allopurinol hypersensitivity reaction: HLA-B * 5801 allele screening **Colchicine, NSAIDs** or **steroids** * Used as prophylaxis when starting ULT to reduce the risk of attacks
25
What is the second-line prophylactic treatment for gout?
**Probenecid** * Uricosuric that is used when XOIs are contraindicated or not tolerated or can be added when the UA level is not at goal despite maximum doses of XOIs * It inhibits reabsorption of UA in the proximal tubule of the nephrone and requires adequate renal function to be effective **Lesinurad** * Uricosuric that is taken with the XOI **Pegloticase** * Recombinat uricase enzyme that converts UA to an inactive metabolite that can be easily excreted * It is reserved for severe, refractory disease
26
Allopurinol - brand/generic, MOA, warnings, SEs
Allopurinol **(Zyloprim, Aloprim)** **MOA:** * Decrease uric acid production **Warnings:** * Hypersensitivity reactions (severe rash, including SJS/TEN, DRESS); HLA-B * 5801 testing prior to use if high risk and do not use if positive * Hepatotoxicity **Side effects:** * Rash, acute gout attacks, nausea Use with colchicine or an NSAID for the first 3-6 months due to the high rate of gout attacks
27
Febuxostat - brand/generic, MOA, BW, warnings, SEs
Febuxostat **(Uloric)** **MOA:** * Decrease UA production **Boxed warnings:** * Use should be limited to those who cannot tolerate allopurinol as there is an increased risk of CV death compared to allopurinol in patients with CV disease **Warnings:** * Hepatotoxicity * Serious skin reactions (SJS/TEN, DRESS) **Side effects:** * Increased LFTs Use with colchicine or an NSAID for the first 3-6 months due to the high rate of gout attacks
28
Uricosurics - MOA, brand/generic
**Probenecid** * Increases beta-lactam levels **Lesunurad** * Taken with allopurinol or febuxostat **MOA:** * Inhibit reabsorption of UA in the kidneys, which increases UA excretion
29
XOI - DIs
* They increase the concentration of mercaptopuriine, the active metabolite of azathioprine
30
Probenecid - DIs
* ADRs can occur when used with beta-lactams to increase the concentration
31
Recombinant Uricase - MOA, BWs, CIs
Pegloticase **(Krystexxa)** **MOA:** * Converts UA to allantoin, which is excreted **Boxed warnings:** * Anaphylactic reactions - premedicate with antihistamines and steroids **Contraindications:** * G6PD deficiency * Do not use in combination with allopurinol, febuxostat or probenecid (increases risk of anaphylaxis)
32
Which medication is used to treat tumor lysis syndrome (TLS)?
* Rasburicase (Elitek) - a urate-oxidase enzyme
33
When is the use of rasburicase contraindicated?
* G6PD deficiency

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