Gout Flashcards

1
Q

Gout

A

Inflammatory Arthritis
Purines (from diet / tissue breakdown) -> Uric Acid
Uric Acid - (uricase not in humans) -> allantoin

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2
Q

Uric Acid Levels

A

Uric Acid (UA) is soluble at concentrations < 6.7 mg/dL
Crystals deposit in joints
• Phagocytosed triggering an immune response

Excess serum uric acid caused by:
Overproduction of urate
Underexcretion of urate

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3
Q

*Gout and Disease States

A

Should Know

The following diseases promote hyperuricemia:
• Insulin resistance (DM)
• Hyperlipidemia
• Obesity
• Renal insufficiency/Chronic Kidney Disease
• Hypertension
• Organ transplantation
• CHF

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4
Q

Diet and Gout - Hyperuricemic Foods

A

Meat (particularly organ meats)
Seafood
Beer and Liquor (particularly beer and spirits > wine)
Soft Drinks (high sugar)
Fructose (also high fructose corn syrup)

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5
Q

Diet and Gout - Uricosuric Foods

A

Uricosuric = LOWER Uric acid levels

Coffee
Dairy
Vitamin C

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6
Q

Medications and Gout - Hyperuricemic Agents

A

Thiazide Diuretics
Loop Diuretics
Nicotinic Acid
Aspirin (<1g/day)
Cyclosporine, Tacrolimus, Pyrazinamide, Levadopa, Ethambutol

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7
Q

Medications and Gout - Uricosuric Agents

A

Uricosuric = Uric Acid LOWERING agents

Losartan
Fenofibrate

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8
Q

Podagra

A

First metatarsophalangeal (Big toe) joint involvement most common

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9
Q

Gout flare (attack)

A

Rapid onset (within 24 hours) of severe pain, erythema and swelling in a single or multiple joints

Podagra

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10
Q

Tophi

A

Mass of urate deposits in bone, cartilage, joints or tissues

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11
Q

Gout Diagnosis

A

Diagnosed by synovial fluid aspiration and identification of monosodium urate crystals (not routinely done in outpatient)
• Associated with a serum uric acid > 6.8 mg/dL
• However, serum uric acid may not be elevated in an acute attack
• Not all patients with hyperuricemia will develop gout
Flare/attack presentation generally confirms diagnosis - doesn’t require synovial fluid aspiration

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12
Q

Acute Gout

A

Goals of therapy: Reduce pain and duration of attacks

Anti-inflammatory agents:
• NSAIDs
• Colchicine
• Corticosteroids
• Oral, intraarticular

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13
Q

NSAIDs

A

COX inhibition
One not more efficacious than another
-Indomethacin, naproxen and sulindac have FDA approved labeling for gout
Timing of administration (<24 hours) more important to treatment success than choice of agent
Resolution of symptoms usually within 5-8 days of initiation

Avoid use in:
• Renal insufficiency/failure
• Bleeding disorders/anticoagulated patients
• Peptic ulcer disease
• CHF
• Older adults (≥75 years)

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14
Q

Colchicine

A

MOA: inhibition of β-tubulin polymerization into microtubules (part of regular cell division). Also prevents activation, degranulation, and migration of neutrophils
Dosage: 1.2 mg (2 tabs) po x 1 then 0.6 mg 1 hour later
Adverse Effects: Often causes GI symptoms
• Hematologic abnormalities
Rhabdomyolysis
• Renal dysfunction and elderly patients are at increased risk
• Concomitant use of 3A4 inhibitiors, P-gp inhibitors, fibrates, and statins may increase the risk of myopathy
• Dose adjust in renal/hepatic impairment
• CrCl < 30 ml/min
• Hepatic impairment

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15
Q

Colchicine Interactions

A

Concomitant CYP 3A4 and P-gp inhibitor users
• Dose adjustments necessary
Concurrent use of colchicine and P-gp or strong CYP3A4 inhibitors is contraindicated in renal impairment &/or hepatic impairment

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16
Q

Strong CYP3A4 Inhibitors - Recognize DDI with what Gout therapy?

A

DDI with Colchicine

Only including must knows:
Clarithromycin
Darunavir/ritonavir
Itraconazole
Ketoconazole

Acute Gout Flares: Single 0.6-mg dose followed by 0.3 mg 1 hour later; dose to be repeated no earlier than 3 days

Prophylaxis of Gout Flares: 0.3 mg once every other day to 0.3 mg once daily

17
Q

Moderate CYP3A4 Inhibitors - Recognize DDI with what Gout therapy?

A

DDI with Colchicine
Must knows:
Diltiazem
Erythromycin
Fluconazole
Verapamil

Acute Gout Flares: Single 1.2-mg dose; dose to be repeated no earlier than 3 days

Prophylaxis of Gout Flares: 0.3-0.6 mg daily (0.6-mg dose may be given as 0.3 mg twice daily)

18
Q

P-glycoprotein inhibitors - DDI with which Gout medication?

A

Colchicine DDI
Must know agents for exam:
Cyclosporine
Amiodarone
Ranolazine

Acute Gout Flares: Single 0.6-mg dose; dose to be repeated no earlier than 3 days

Prophylaxis of Gout Flares: 0.3 mg once every other day to 0.3 mg once daily

19
Q

Corticosteroids

A

MOA: Reduces polymorphonuclear leukocyte migration, suppresses
the lymph system
• Immune suppression and anti-inflammatory effects
Similar efficacy to NSAIDs in trials
Prednisone 30-60mg po qd for 2 days with taper over 10 days
Methylprednisolone dose pack

20
Q

MUST KNOW: Intra-articular triamcinolone doses

A

• Large joint (eg, knee): 40 mg as a single dose

• Medium joint (eg, wrist, ankle, elbow): 30 mg as a single dose

• Small joint (eg, toe, finger): 10 mg as a single dose

21
Q

Corticosteroids Use Populations

A

Consider alternative if DM, CHF or severe GERD or PUD
- Increases BG
Safe for use in renal impairment

22
Q

Chronic Therapy Agents/Goals

A

Goals of therapy: Prevent future attacks and hyperuricemic sequlae by maintaining SUA < 6.0

Xanthine - (xanthine oxidase) -> Uric Acid - (uricase) -> Allantoin

Xanthine Oxidase Inhibitors: Allopurinol, Febuxostat
Uricosurics: Probenecid
Synthetic Uricase: Pegloticase

23
Q

Allopurinol

A

Xanthine Oxidase Inhibitor
Can be used regardless of whether there is overproduction
ADRs:
Rash
• Occurs in ~2% of patients
Potentially increased by coadministration with amoxicillin, ampicillin, thiazides, ACE-I
Probably best to d/c the drug
• Mild rash can progress to Stevens Johnson Syndrome
Allopurinol Hypersensitivity (DRESS syndrome)
• Drug Rash with Eosinophilia and systemic symptoms
• Rash + fever + eosinophilia + hepatitis
• Occurs in 0.1% of patients
• Rate of death 20-25%
• Immediately d/c the drug

24
Q

Allopurinol DDI and Dosing

A

Warfarin - can still use but monitor INR for increased bleed risk
6-MP, azathioprine, theophylline - these meds not used often
amoxicillin, ampicillin, thiazides, ACE-I - increase risk of rash

Dosing:
Starting dose: 50-100 mg qday
• 100 mg po qd starting dose: normal renal function
• 50 mg po qd in CKD stage 4 or worse
• Increase q 2-5 weeks to target < 6 mg/dL
• May have to increase up to 800mg to achieve target SUA
• Can go above 300mg po qday even in renal impairment despite renal dosage adjustment PI recommendations - would just have to monitor more carefully

25
Q

Febuxostat (Uloric)

A

Chemically engineered, selective xanthine oxidase inhibitor
• Not structurally related to allopurinol

Dosing: 40 mg once daily; may increase to 80 mg once daily in patients who do not achieve a serum uric acid level <6 mg/dL after 2 weeks
• No dosage adjustments required for mild-moderate renal or hepatic impairment
• Severe hepatic impairment or CrCl< 30 ml/min
• Not studied, caution for use
If a gout flare occurs, febuxostat does not need to be discontinued (neither does allopurinol)

26
Q

Febuxostat (Uloric) ADR/CI

A

Most common ADRs: Headache, arthralgias, abdominal pain, nausea, abnormal LFTs, flushing and dizziness
BBW: Cardiovascular death: Febuxostat should only be used in patients who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or when treatment with allopurinol is not advisable
CI: Patients concurrently receiving 6-MP, azathioprine and theophylline (same 3 as allopurinol because xanthine oxidase is involved in their metabolism)

27
Q

Probenecid

A

MOA: Competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby promoting its excretion and reducing serum uric acid levels
Dosing: 250 mg twice daily for 1 week; may increase to 500 mg twice daily; if needed, may increase to a maximum of 2 g/day (increase dosage in 500 mg increments every 4 weeks).
Renal dosing
Avoid use in CrCl < 50 ml/min
Avoid with history of nephrolithiasis

Avoid concomitant use of probenicid and:
• Penicillin, Methotrexate, Carbapenems (Doripenem, Meropenem)
• Increased concentration due to decreased renal secretion
• Salicylates (aspirin)
• Decreased efficacy of probenecid

28
Q

Pegloticase

A

Pegylated recombinant uricase
I.V. 8 mg every 2 weeks over at least 2 hours
Infusion related reactions common (Black box warning)
• Anaphylaxis and infusion reactions during and after therapy
• Generally, occur within first 2 hours
• Pre-med with antihistamines and corticosteroids

29
Q

Chronic Therapy - Who? When?

A

Not all patients require chronic therapy solely because elevated UA level
Lifestyle modification recommended for all patients, regardless of disease activity
Chronic Therapy = UA lowering therapy + Flare prophylaxis
• UA lowering therapy initiation can illicit flares
• Prophylactic flare therapy should be given concomitantly with UA lowering therapy (ULT)
Chronic therapy should not be stopped during flare

Indications for pharmacologic treatment:
• ≥1 subcutaneous tophi, radiographic evidence of damage attributable to gout; OR frequent flares (≥2/year)

May consider treatment:
• History of >1 attack, but <2 attacks per year
• Those with first gout flare with the following characteristics
• CKD stage ≥3
• [UA] > 9 mg/dL
• Urolithiasis

30
Q

Gout Flare - Oral Prednisone Dose

A

0.5mg/kg for 5-10 days then stop

31
Q

See slides for treatment algorithm images, but most content is here

A

See slides