60. Gout Flashcards by Yerin M

Gout is a type of arthritis caused by a buildup of____ primarily in the joints

uric acid (UA) crystals

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Uric acid is produced as an end-product of ____ metabolism

Purine

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Gout typically occurs in 1 joint, most often the ___ joint

Metatarsophalangeal joint (MTP, the big toe)

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In addition to a uric acid level, ___ can be evaluated to identify if UA crystals are present

sample of synovial (joint) fluid

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Risk factors for gout

Male sex
Obesity
Excessive alcohol consumption (particularly beer)
Others: HTN, CKD, lead intoxication, advanced age, and using meds that increase UA levels

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Drugs that increase uric acid

Aspirin, lower doses
Calcineurin inhibitors (tacrolimus, cyclosporine)
Diuretics (loop and thiazides)
Niacin
Pyrazinamide
Select chemotherapy (with tumor lysis syndrome)
Select pancreatic enzyme products

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Foods to avoid to lower risk of gout

Organ meats
High-fructose corn syrup
Alcohol

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T/F: treat hyperuricemia with drugs even if asymptomatic

False - asymptomatic hyperuricemia is not to be treated with drugs

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Ppx gout drugs are used to lower UA levels, with a goal UA level of < ___

6mg/dL

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What meds can be used to treat gout acute pain

Colchicine
Steroids (often intra-articular injections)
NSAIDs (often high starting dose)

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What meds can be used as gout ppx?

Xanthine oxidase inhibitor (XOI): allopurinol (preferred) or febuxostat

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An acute gout flare can occur when an XOI is started so give initially with ___ or ___

colchicine or an NSAID

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If XOI didn’t work well enough and UA remains > 6 mg/dL, what can you add on?

Add on probenecid or lesinurad to daily XOI
Replace XOI with IV pegloticase (Krystexxa)

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Colchicine (Colcrys) treatment dosing

Two 0.6mg tablets followed by 0.6mg in 1 hr (do NOT exceed total of 1.8mg in 1 hr)

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When using colchicine, do NOT exceed total of ___mg in 1 hr

1.8mg in 1 hr

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Contraindications for colchicine

Do NOT use in combo with P-gp or strong CYP3A4 inhibitor with renal and/or hepatic impairment

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Warnings for colchicine

Myelosuppression
Do not use with cyclosporin, diltiazem, verapamil, gemfibrozil, or statins – increase myopathy risk

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Side effects for colchicine

Diarrhea, nausea, myopathy, neuropathy (dose-dependent), decrease vit B12

Use colchicine within ___hrs of symptom onset (for treatment)
Wait ___ hrs after treatment dose before resuming prophylaxis dosing

36 hrs
12 hrs

Which NSAIDs are used in gout?

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

Which steroids are used in gout?

Prednisone, prednisolone
Methylprednisolone (Medrol, Solu-Medrol)

Methylprednisolone (Medrol, Solu-Medrol) can be used intra-articular if ___large joints are involved

1-2

Acute side effects of steroids

Increased BG, BP, insomnia, appetite

Fatal toxicity can occur if colchicine is combined with strong CYP ___ inhibitors or strong P-gp inhibitor

3A4
Colchicine is major substrate of 3A4 and p-gp

When starting chronic uric acid lowering treatment, ____ should be used as prophylaxis to reduce risk of attacks

colchicine, steroids, or NSAIDs

Pharmacogenomic consideration with allopurinol use

HLA-B*5801 allele screening should be done for pts at high risk of severe hypersensivity reaction (including certain Asian groups)

____ is a uricosuric and a second-line treatment that can be used if XOIs are contraindicated or not tolerated or added when UA level is not at goal

Probenecid Alternative lesinurad (taken WITH XOI)

Probenecid MOA

inhibits reabsorption of UA in the proximal tubule of the nephron (increase UA excretion) Requires adequate renal function to be effective

____ a recombinant uricase enzyme, is reserved for severe, refractory disease

Pegloticase

Xanthine oxidase inhibitors MOA

decrease uric acid production

Warnings for allopurinol (Zyloprim, Aloprim)

Hypersensitivity reactions, including severe rash (SJS/TEN, DRESS) HLA-B*5801 testing prior to use if high risk (esp for Asian pts), do not use drug if + ) Hepatotoxicity, bone marrow suppression

Side effects of allopurinol (Zyloprim, Aloprim)

Rash, acute gout attacks, nausea, diarrhea, increased LFTs

D/t high rate of gout attacks when beginning allopurinol or febuxostate, use with colchicine (0.6mg once or twice daily) or an NSAID for the first ____

3-6 months

Febuxostat (Uloric) Boxed warning

Increased risk of CV death compared to allopurinol in pts with established CV disease Use should be limited to those who cannot tolerate allopurinol or if not effective

Uricosurics MOA

inhibit reabsorption of uric acid in the kidneys, increase UA excretion

Probenecid can be used to (increased/decrease) beta-lactam levels

Increase levels by decreasing beta-lactam renal excretion

Recombinant uricase MOA

Converts uric acid to allantoin (excreted)

Pegloticase (Krystexxa) dosing frequency

IV every 2 weeks

Boxed warning for pegloticase (Krystexxa)

Anaphylactic reactions - premedicate with antihistamines and steroids (higher risk with UA > 6) Life-threatening hemolytic reactions and methemoglobinemia may occur with G6PD deficiency

Contraindications for pegloticase (Krystexxa)

G6PD deficiency

Do NOT use pegloticase (Krystexxa) in combo with ____ (increased risk of anaphylaxis)

allopurinol, febuxostat, or probenecid

Do not use ___ or ___ with febuxostat and use caution combining these with allopurinol

Mercaptopurine (active metabolite of azathioprine) or azathioprine Allopurinol and febuxostat increase conc of mercaptopurine

___ is a urate-oxidase enzyme used in the treatment of tumor lysis syndrome (TLS). Contraindicated with ___ deficiency.

Rasburicase (Elitek) G6PD