Gout

Question 1

What is gout and its cause?

Answer 1

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

Question 2

How is UA produced?

Answer 2

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

Question 3

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

Answer 3

• True

Question 4

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

Answer 4

• Asymptomatic
• Crystallize
• Painful

Question 5

What are the characteristics of a gout attack?

Answer 5

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

Question 6

What is used to identify UA crystals in the body?

Answer 6

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

Question 7

What are the risk factors for gout?

Answer 7

• Male sex
• Obesity
• Excessive alcohol consumption

Question 8

List drugs that increase UA

Answer 8

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

Question 9

T/F: Asymptomatic hyperuricemia is not treated with drugs

Answer 9

• True

Question 10

The drugs used for acute attacks target __ and __.

Fill in the blanks

Answer 10

• Pain
• Inflammation

Question 11

Why prophylactic drugs are used?

Answer 11

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

Question 12

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

Answer 12

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

Question 13

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

Answer 13

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)

Question 14

How do you initially treat acute gout attack?

Answer 14

• 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

Question 15

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

Answer 15

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

Question 16

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

ULT: allopurinol, febuxostat

Answer 16

• True

Question 17

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

Answer 17

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

Question 18

NSAIDs - medications

Answer 18

• Indomethacin (Indocin)
• Naproxen (Aleve)
• Celecoxib (Celebrex)

Question 19

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

Fill in the blanks

Answer 19

• Renal
• CVD

Question 20

Steroids - formulations, SEs

Answer 20

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

SEs:
* ↑BG,↑BP, ↑ appetite, insomnia

Question 21

Steroids: medications

Answer 21

• Prednisone/Prednisolone
• Methylprednisolone (Medrol, Solu-Medrol)

Question 22

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

Answer 22

• True

Question 23

List colchicine DIs

Answer 23

Fatal toxicity: CYP3A4 inhibitors or strong P-gp inhibitors

Question 24

What is the first-line prophylactic treatment for gout?

Answer 24

**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

Question 25

What is the second-line prophylactic treatment for gout?

Answer 25

**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

Question 26

Allopurinol - brand/generic, MOA, warnings, SEs

Answer 26

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

Question 27

Febuxostat - brand/generic, MOA, BW, warnings, SEs

Answer 27

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

Question 28

Uricosurics - MOA, brand/generic

Answer 28

**Probenecid** * Increases beta-lactam levels **Lesunurad** * Taken with allopurinol or febuxostat **MOA:** * Inhibit reabsorption of UA in the kidneys, which increases UA excretion

Question 29

XOI - DIs

Answer 29

* They increase the concentration of mercaptopuriine, the active metabolite of azathioprine

Question 30

Probenecid - DIs

Answer 30

* ADRs can occur when used with beta-lactams to increase the concentration

Question 31

Recombinant Uricase - MOA, BWs, CIs

Answer 31

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)

Question 32

Which medication is used to treat tumor lysis syndrome (TLS)?

Answer 32

* Rasburicase (Elitek) - a urate-oxidase enzyme

Question 33

When is the use of rasburicase contraindicated?

Answer 33

* G6PD deficiency