24 - Gout Flashcards
1
Q
Definition of gout
A
Group of heterogeneous diseases characterized by arthropathy resulting from the deposition of urate crystals in and around the joints
2
Q
Modifiable risk factors for gout
A
- Hyperuricemia
- Hypertension, obesity, diabetes
- Alcohol consumption (binge drinking can precipitate attacks in those susceptible)
- High purine intake
- Drugs
3
Q
Non-modifiable risk factors for gout
A
- Chronic kidney disease
- Male gender
- Age
- Genetics, family hx
4
Q
What is hyperuricemia and how can it occur?
A
- Definition = serum uric acid > 480 umol/L in males or > 420 umol/L in females
- Etiology = overproduction and/or underexcretion
5
Q
How is uric acid produced?
A
- Dietary intake, breakdown of tissue nucleic acids, and de novo synthesis => purines (guanine, adenine)
- Degradation of purines => uric acid
6
Q
Do the majority of gout px have uric acid overproduction or underexcretion?
A
Underexcretion
7
Q
What can cause uric acid overproduction?
A
- Diet
- Tissue/cell breakdown
- Metabolic derangement
8
Q
What can cause uric acid underexcretion?
A
Renal abnormalities (67% of uric acid excreted by kidneys)
9
Q
Describe renal excretion of uric acid
A
- 100% of uric acid enters glomerulus
- Majority is reabsorbed, leaving 0-2% in the proximal tubule
- Then some is secreted back into proximal tubule and reabsorbed again leaving 8-12% to be excreted
10
Q
Factors altering renal excretion of uric acid
A
- Decreased GFR
- Decreased active secretion of uric acid (ex: salicylates < 2 g/day, loop and thiazide diuretics, acute EtOH)
- Increased post-secretory resorption (ex: dehydration, high dose ASA)
- Undefined (ex: HTN, hyperparathyroidism, cyclosporine)
11
Q
What is monosodium urate (MSU)?
A
- Ionized form of uric acid; most common form of uric acid in the blood?
- Limited solubility in plasma (even lower solubility at lower temps and the toes are some of the coldest parts of the body)
12
Q
Pathophysiology of gout
A
Saturation of synovial fluid w/ uric acid -> crystal formation -> activation of inflammatory response -> leukocytes and macrophages -> proteolytic enzymes, prostaglandins, leukotrienes; activation of clotting, kininogen, plasminogen and complement cascades -> damage to articular cartilage and injury to soft tissue
13
Q
Clinical characteristics of acute gouty arthritis
A
- Sudden onset of warmth, swelling, erythema, and unbearable joint pain
- 50% of first attacks occur at metatarsophalangeal joint of the great toe only
- 90% will have involvement of this site sometime during their disease
- 10% of first attacks involve 2 or more joints
- Systemic sx such as fever, chills & malaise may be present
- Untreated sx last 3-14 days before spontaneous recovery
14
Q
Joints affected in gout
A
- Most common = toe, instep, ankle
- Medium prevalence = heel, knee, wrist
- Low prevalence = finger, elbow
15
Q
Precipitating factors of gout
A
- Stress or trauma at the joint
- Alcohol (binge drinking)
- Infection, surgery
- Rapid lowering of serum uric acid
- Drugs that increase uric acid
16
Q
Diagnosis of acute gout
A
Demonstration of sodium urate crystals in affected joint (take a sample of the fluid from the affected joint and analyze for sodium urate crystals)
17
Q
What are intercritical periods?
A
- Periods between attacks
- 2nd attack w/in 6 months to 2 years
- W/ subsequent attacks, intercritical periods become shorter
- Attacks become polyarticular, more severe and longer lasting
18
Q
Chronic complications of gout
A
- Nephrolithiasis
- Gouty nephropathy (acute uric acid nephropathy or chronic urate nephropathy)
- Tophi formation
19
Q
What is chronic tophaceous gout?
A
- Chronic urate deposits in cartilage, tendons, synovial membranes
- Common sites = toe, fingers, wrists, ears, knees, achilles tendon
- Occur when intercritical periods no longer pain free (10 years of acute intermittent gout)
- 50-70% of px if hyperuricemic therapy not initiated
- W/ the use of hypouricemic agents, prevalence decreases to 3-21%
- Joints persistently uncomfortable and swollen
- Acute gout attacks continue to occur
20
Q
Gout tx goals
A
- Relieve pain and inflammation w/in 48 h of an acute attack
- Complete resolution of sx in 7 days
- Reduce uric acid levels to < 360 umol/L
- Prevent recurrent attacks of gouty arthritis
- Prevent chronic complications of gout
21
Q
Gout management approach
A
- Treat acute flare rapidly w/ an anti-inflammatory agent
- Initiate urate-lowering therapy to achieve serum urate < 6 mg/dL; use concomitant anti-inflammatory prophylaxis for up to 6 months to prevent mobilization flares
- Continue urate-lowering therapy to control flares and avoid continual crystal deposits; use for at least 3-6 months while serum urate levels normalize
22
Q
Pharm options for acute gouty arthritis and prophylactic therapy
A
- Acute gouty arthritis -> NSAIDs, COX 2 inhibitor, colchicine, corticosteroids
- Prophylactic therapy -> short term = colchicine 0.6 mg BID, low dose NSAIDs; long term = allopurinol, febuxostat
23
Q
Non-pharms for gout
A
- Avoid drugs capable of inducing hyperuricemia and gout (ex: loop and thiazide diuretics, beta blockers, ACE inhibitors salicylates < 2 g/day, pyrazinamide, nicotinic acid, omeprazole, cyclosporine and tacrolimus)
- Can use Ca channel blockers or losartan for HTN
24
Q
NSAIDs for gout
A
- Use recommended maximal doses at the first sign of an attack
- Lower dose as sx resolve (4-5 days)
- Start ASAP at max. dose then taper
- Should also get PPI for GI protection
- Continue until joint pain has resolved totally for at least 48 h (7-10 days)
- No evidence that any given NSAID is superior
- Pt should have some on hand for next acute attack (b/c having to see the Dr for every attack slows down initiation of therapy)
25
Q
NSAID doses for gout
A
- Anti-inflammatory dose different from analgesic dose
- Ibuprofen = 600 mg QID
- Naproxen = 750 mg then 500 mg BID
- Celecoxib = 400 mg q12h x 2 days then 200 mg BID
26
Q
Colchicine dosing for gout
A
- Traditional dosing = 0.5-0.6 mg q1h or 1-1.2 mg q2h until significant improvement of pain or GI toxicity
- Maximum total dose = 8-10 mg
- *Should use 1.2 mg followed by 0.6 mg in 1 h!!
- Tested 1.2 mg followed by 0.6 mg in 1 h vs. 1.2 mg followed by 0.6 mg per h x 5 h (total dose = 4.8 mg) -> conclusion = no difference in efficacy (pain reduction) but high dose caused significantly more GI effects
- Old dosing = 1.2 mg followed by 0.6 mg/h for 5 h (don’t use this; will cause severe diarrhea, N/V)
27
Q
Colchicine drug interactions
A
- CYP 3A4 inhibitors (diltiazem, verapamil, itraconazole, fluconazole, clarithromycin)
- Statins and fibrates increase myalgia
28
Q
Colchicine summary
A
- Start ASAP after the onset of a flare
- Only use low dose, NOT traditional dosing
- Px receiving prophylaxis therapy may receive tx dosing; wait 12 h and resume prophylaxis
- Dosage adjustment needed w/ 3A4 inhibitors and for CrCl < 30 mL/min
29
Q
Systemic corticosteroids for gout (dose, role, and when to expect pain relief)
A
- Prednisone 20-40 mg/day x 4 days
- Taper over 1-2 weeks
- Pain relief w/in 12-48 h
- Used for refractory attacks or when other agents contraindicated
30
Q
IA corticosteroid injection for gout
A
- Septic arthritis needs to be ruled out first
- Single injection of methylprednisolone acetate 10-40 mg or dexamethasone 0.8-4 mg
- Pain relief w/in 12-24 h – lasts for duration of attack
31
Q
Prophylactic therapy for gout
A
- 7% of px won’t experience another attack for 10 years or more
- Must consider -> severity of acute attack, response to tx, serum urate concentrations, and another change being made to decrease UA
32
Q
Short term prophylactic therapy for gout
A
- Px w/ no tophi and normal or slightly elevated uric acid levels
- Colchicine 0.6 mg BID
- Low dose NSAIDs
- D/c drugs if uric acid normal and pt is sx free for 6 months
33
Q
When to consider urate lowering therapy
A
- Recurrent attack, arthropathy, or X-ray changes
- Tophi
- Gout w/ CKD
- Recurring renal stones
- Need for ongoing diuretic tx (after 1st gout attack)
34
Q
Goals of urate lowering therapy
A
- Uric acid < 360 umol/L
- Can we go too low? (under investigation)
35
Q
Benefits of uric acid levels < 360 umol/L
A
- Reduced frequency of attacks
- Reduced tophus size
- Deplete crystal stores in synovial fluid
- Improved renal function w/ reduction of NSAID use
- Slows progression of existing renal disease
36
Q
Allopurinol for gout (dose, MOA)
A
- Blocks conversion of hypoxanthine to xanthine and xanthine to uric acid
- Misconception about dosing (60% of px are under dosed)
- Fear of allopurinol hypersensitivity syndrome and renal insufficiency limit its appropriate use
- Approved from 100-800 mg
- ~40% achieve goal urate levels w/ 300 mg/day or less
37
Q
Allopurinol hypersensitivity syndrome (AHS)
A
- Isolated rash may occur in up to 2% of px
- Severe cutaneous reactions, fever, eosinophilia, leukocytosis, renal involvement and hepatitis
- Risk factors = recent onset of therapy, CKD, thiazide use
38
Q
Allopurinol summary
A
- Initiate therapy 3+ weeks after resolution of acute attack
- Initiate prophylaxis 2 weeks before start
- Starting dose = 100 mg OD (50 mg OD if CrCl < 50 mL/min)
- Titrate dose up by 100 mg q1month until target of UA < 360 umol/L
- Can dose beyond 300 mg/day if needed
- Don’t d/c during future flares
- *Avoid in combo w/ azathioprine or 6-MP
39
Q
How to initiate urate lowering therapy
A
- Initiation will increase frequency of acute attacks
- Initiate prophylactic therapy for the first 6 months w/ colchicine 0.6 mg OD (if CrCl < 50 mL/min) or BID (if CrCl > 50 mL/min), or naproxen 250 mg BID
40
Q
Other uricosuric agents (increase excretion of uric acid in urine)
A
- Probenicid and sulfinpyrazone -> require BID or TID dosing, many drug interactions, ineffective as CrCl decreases
- Off label agents -> losartan, fenofibrate
41
Q
Febuxostat for gout
A
- Potent non-purine selective inhibitor of xanthine oxidase
- Found to be superior to allopurinol in the reduction of uric acid
- Problem w/ study was that allopurinol dose fixed at 100-300 mg
- Dosing -> recommended initial dose of 40 mg daily; may titrate to 80 mg daily after 2 weeks if serum uric acid > 360 umol/L
42
Q
Febuxostat or allopurinol?
A
- Both agents effective in reduction of uric acid (if a treat-to-target approach is used)
- Febuxostat appears to be tolerated in px w/ AHS
- Regardless of the agent, prophylaxis w/ colchicine or NSAIDs should be used for at least 6 months after initiation of urate lowering therapy
- Febuxostat not covered by pharmacare or private insurance
43
Q
Clinical pearls for gout
A
- Uric acid levels can be normal during acute attack, so check levels 2-3 weeks later
- NSAIDs -> max dose then taper and d/c 2 days after resolution of sx
- Use only low dose colchicine for acute attacks
- Have drug at home in preparation for next attack
- Start urate lowering agent 2-3 weeks post-acute attack; start low and go slow
- Don’t forget to use prophylaxis for 6 months
- Remember to continue urate lowering therapy in acute attacks
- Vitamin C 500-1000 mg is effective in reducing UA > 10% in 2 months
- Increase dairy product intake
- Spend time addressing the comorbidities of gout
44
Q
Counselling tips for acute attacks of gout
A
- NSAIDs -> counsel pt to take w/ food to reduce stomach upset
- Colchicine -> review dosing regimen to avoid potential toxicity
- Steroids -> review tapering regimen and supply a calendar
- Reassure pt that the pain should improve over the next 24-36 h
- Adjunctive tx w/ acetaminophen +/- 8 mg codeine may be helpful initially
- Counsel pt to reduce general alcohol consumption and to ensure they have comfortable footwear
- Call pt in 2-3 days to check for improvement and monitor AE
45
Q
Counselling tips for prophylaxis w/ antihyperuricemic agents
A
- Ensure pt starts w/ low doses and is clear on how to titrate
- Ensure pt has a supply of a prophylactic NSAID or colchicine on hand to use concurrently while starting, to decrease the risk of an acute attack
- Counsel pt to watch for potential AE and report them to pharmacist or physician
- Inform pt that routine bloodwork will be required to monitor how well the medication is working and to avoid potential AE
