Gout Flashcards
1
Q
Gout
A
- Disease spectrum including hyperuricemia and recurrent attacks of acute painful inflammatory arthritis
- Affects approximately 4% of adults
- “Disease of kings”
2
Q
Gout Risk Factors
A
- High purine diet (red meals, shellfish)
- Alcohol consumption
- Male
- Obesity
- Genetics
- Renal impairment
3
Q
Uric Acid Metabolism
A
- Byproduct of purine metabolism
- Waste product with no biological purpose
- Exclusively occurs in humans/primates which have a nonfunctional urate oxidase (uricase enzyme)
4
Q
Uricemia
A
- Overproduction (~10%) and underexcretion (~90%)
- Normal levels vary by gender
- Male: 3.4-7.0 mg/dL
- Female: 2.4-6.0 mg/dL
- Hyperuricemia: Uric acid >7 mg/dL (supersaturated)
- Higher uric acid levels = higher risk of gout
- May be an asymptomatic condition
5
Q
Clinical Presentation
A
- Rapid onset
- Excruciating pain
- Erythema
- Swelling
- Monoarticular vs polyarticular
- Tophus - deposits of urate crystals
6
Q
Joints Affected by Gout
A
- Generally 1st metatarsophalangeal joint is most affected (MTP) - big toe joint
- Typically affects small joints like insteps, ankles, wrists, fingers, elbows
7
Q
Diagnosis Considerations
A
- Symptoms
- History and risk factors
- Hyperuricemia
- Imaging and arthrocentesis
8
Q
Non-pharm Therapy
A
- Education: attacks are spontaneous and resolve in 3-10 days
- Lifestyle changes
- Joint rest: 1-2 days
- Topical therapy: apply ice
9
Q
Gout Lifestyle Changes
A
- Reduce purine rich food intake
- Reduce alcohol intake
- Increase water intake
- Weight loss
10
Q
Pharmacological Therapy - Treatment
A
- Terminate acute attack
- Initiate within 24 hours of symptoms onset
11
Q
Pharmacological Therapy - Prophylaxis
A
- Prevent recurrent attacks
- Should not be initiated during an acute attack
12
Q
Treatment Basics
A
- Monotherapy: mild to moderate pain on one major joint or a few small joints
- Dual Therapy: Severe pain with polyarticular or multiple large joints
- Concurrent prophylatic therapy should NOT be interrupted
- Educate about recurrent attacks and to self-initiate treatment based on symptoms
13
Q
Gout Treatment Agents
A
- NSAIDs
- Corticosteroids
- Colchicine
14
Q
NSAIDs
A
- Acceptable first line therapy
- Little evidence to support one agent over another
- Indomethacin is the most studied for gout - drug-of-choice for termination of acute attacks
- High-doses as early as possible for as short a duration as possible
- CAUTION: renal impairment, high-risk for GI bleed/ulceration, severe heart failure
15
Q
Common NSAID Regimens
A
- Indomethacin (Indocin) - 50 mg PO TID
- Naproxen (Naprosyn/Aleve) - 500 mg PO BID
- Sulindac - 200 mg PO BID
Initiate within 24-48 hours of symptoms onset and discontinue 2-3 days after resolution (usually 5-7 days total)
16
Q
Corticosteroids
A
- Acceptable first line therapy
- Similar efficacy to NSAIDs
- By mouth and intra-articular options
17
Q
Oral Corticosteroids Options
A
- Prednisone
- 0.5 mg/kgday PO for 5-10 days
- 30-60 mg/day PO until symptom improvement then taper over 7-10 days
- Methylprednisone dose oack is also an option
18
Q
Intra-articular Corticosteroid Options
A
- Methylprednisolone (Solu-Medrol) or Triamcinolone (Kenalog-10 or -40)
- DO NOT use if suspicion for infection/septic joints
- Usually limited to 1-2 joints, use IV/IM if multiple joints involved
19
Q
Colchicine
A
- Colcrys
- MoA: neutrophil inhibition resulting in reduced inflammation
- Acceptable first line if started within 36 hours of attack onset
- Can be used as a prophylatic at low doses (abortive at high doses)
- Many patients respond favorably bu
- Falling out of favor due to adverse reactions/toxicities
20
Q
Colchicine Dosing/Toxicities
A
- Traditional: 1.2 mg followed by 0.6 mg q2h until symptoms subside or GI distress occurs (Max of 4-6 mg/day)
- Colcrys dosing: 1.2 mg followed by 0.6 mg 1 hour later, then 0.6 mg TID until symptoms resolve
- Colcrys dosing has significantly less adverse GI effects
- Toxicities: nausea, vomiting, diarrhea, bone marrow suppression, hepatotoxicity
- Avoid in severe renal/hepatic impaired patients or those with blood dyscrasias
21
Q
Prophylaxis Basics
A
- May not be needed if first episode resolves quickly or if uric acid level minimally elevated
- Recommended if severe attacks occur, uric acid >10 mg/dL, or 2+ attacks per year
- Target uric acid level <6 mg/dL to lower attack frequency/complications
- Should monitor levels every few weeks initially during dose modification then every 6 months
- Initiate 1-2 weeks after acute attack resolution to prevent flare-ups and rebound attacks
22
Q
Prophylatic Agents
A
- Allopurinol
- Febuxostat
- Colchicine
- Probenecid
- Pegloticase
- Lesinurad
23
Q
Allopurinol
A
- Zyloprim
- MoA: XOI (Xanthine Oxidase Inhibitor) to reduce the production of uric acid
- Drug of choice for most patients
- Bridge with prophylatic colchicine or NSAID for acute attack precipitation
- Can continue during acute attacks
24
Q
Allopurinol Dosing
A
- Initial: 100 mg PO QD
- Titration: 100 mg increments every 204 weeks to achieve desired uric acid level
- Usual dose: 300 mg PO QD (max of 800 mg/day)
- Dose reduced in the renally dysfunctioned
25
Allopurinol AE
- Mild: skin rash, N/V/D, headache
- Severe allergic reactions
- Highest risk of severe, possibly fatal, SE in the first few months
26
Febuxostat
- Uloric
- MoA: XOI that reduces production of uric acid
- Non-inferior to allopurinol
- Bridge with prophylatic colchicine or NSAID for acute attack precipitation
- Can continue during acute attacks
- Viable option in patients with allopurinol allergies, intolerance, or failures
27
Febuxostat Dosing
- Initial: 40 mg PO QD
- Titration: increase to 80 mg after 2 weeks to achieve desired uric acid level
- Usual dose: 40-80 mg PO QD (max of 120/day)
- IF CrCl < 30 mL/min then the max dosing is 40 mg PO QD
28
Febuxostat AE
- Mild: skin rash, N/V/D, LFT elevation
| - No allergic reactions
29
Probenecid
- Benemid
- MoA: uricosuric - inhibits tubular reabsorption of uric acid which increases its renal clearance
- Alternative to XOI or additional agent in non-responders
- Bridge with prophylatic colchicine or NSAID for acute attack precipitation
- Can continue during acute attacks
- Other indications: prolong PCN serum levels and neurosyphillis in addition to IM PCN (antibacterial action)
30
Probenecid Dosing
- Initial: 250 mg BID x 7 days
- Titration: increase in 500 mg increments every 4 weeks
- Usual dose: 500-1000 mg PO BID (max of 2000 mg/day)
- Avoid use in CrCl < 50 mL/min and history of renal stones
31
Probenecid AE
-Mild: skin rash, N/V/D, kidney stones
32
Pegloticase
- Krystexxa
- MoA: PEGylated urate oxidase
- Converts uric acid to allantoin
- IV option used for severe debilitating, refractory gout
- D/C PO anti-hyperuricemic agents prior to starting
- Flare prophylaxis is with NSAIDs or colchicine is recommended starting at least 1 week prior to initiation
- Dose: 8 mg IV q2w (expensive!!!)
33
Pegloticase AE
- Infusion reactions
- Allergic reactions
- Gout flares
**Premedicate with antihistamines and corticosteroids**
34
Lesinurad
- Zurampic
- DISCONTINUED
- MoA: selective uric acid reabsorption inhibitor that blocks renal URAT1 transporter
- Used in combination with XOI when goal uric acid levels not achieved with ZOI alone
- XOI therapy is interrupted, lesinurad should be held
- Dose: 200 mg PO QD in combination with XOI (also max dose)
- CI with CrCl < 30 mL/min
- AE: GERD, influenza, increased SCr, gout flares
35
Other Gout Agents
- Fenofibrate
| - Losartan
36
Fenofibrate
- MoA: increases clearance of xanthine
| - Potential add-on to XOI non-responders or patients with hyperlipidemia
37
Losartan
- MoA: promotes renal excretion of uric acid
| - Potential add-on to XOI nonresponders or patients with hyperlipidemia
