Gout Flashcards
Gout
Inflammatory Arthritis
Purines (from diet / tissue breakdown) -> Uric Acid
Uric Acid - (uricase not in humans) -> allantoin
Uric Acid Levels
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
*Gout and Disease States
Should Know
The following diseases promote hyperuricemia:
• Insulin resistance (DM)
• Hyperlipidemia
• Obesity
• Renal insufficiency/Chronic Kidney Disease
• Hypertension
• Organ transplantation
• CHF
Diet and Gout - Hyperuricemic Foods
Meat (particularly organ meats)
Seafood
Beer and Liquor (particularly beer and spirits > wine)
Soft Drinks (high sugar)
Fructose (also high fructose corn syrup)
Diet and Gout - Uricosuric Foods
Uricosuric = LOWER Uric acid levels
Coffee
Dairy
Vitamin C
Medications and Gout - Hyperuricemic Agents
Thiazide Diuretics
Loop Diuretics
Nicotinic Acid
Aspirin (<1g/day)
Cyclosporine, Tacrolimus, Pyrazinamide, Levadopa, Ethambutol
Medications and Gout - Uricosuric Agents
Uricosuric = Uric Acid LOWERING agents
Losartan
Fenofibrate
Podagra
First metatarsophalangeal (Big toe) joint involvement most common
Gout flare (attack)
Rapid onset (within 24 hours) of severe pain, erythema and swelling in a single or multiple joints
Podagra
Tophi
Mass of urate deposits in bone, cartilage, joints or tissues
Gout Diagnosis
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
Acute Gout
Goals of therapy: Reduce pain and duration of attacks
Anti-inflammatory agents:
• NSAIDs
• Colchicine
• Corticosteroids
• Oral, intraarticular
NSAIDs
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)
Colchicine
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
Colchicine Interactions
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
Strong CYP3A4 Inhibitors - Recognize DDI with what Gout therapy?
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
Moderate CYP3A4 Inhibitors - Recognize DDI with what Gout therapy?
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)
P-glycoprotein inhibitors - DDI with which Gout medication?
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
Corticosteroids
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
MUST KNOW: Intra-articular triamcinolone doses
• 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
Corticosteroids Use Populations
Consider alternative if DM, CHF or severe GERD or PUD
- Increases BG
Safe for use in renal impairment
Chronic Therapy Agents/Goals
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
Allopurinol
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
Allopurinol DDI and Dosing
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
Febuxostat (Uloric)
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)
Febuxostat (Uloric) ADR/CI
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)
Probenecid
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
Pegloticase
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
Chronic Therapy - Who? When?
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
Gout Flare - Oral Prednisone Dose
0.5mg/kg for 5-10 days then stop
See slides for treatment algorithm images, but most content is here
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