24 - Gout Flashcards
(45 cards)
Definition of gout
Group of heterogeneous diseases characterized by arthropathy resulting from the deposition of urate crystals in and around the joints
Modifiable risk factors for gout
- Hyperuricemia
- Hypertension, obesity, diabetes
- Alcohol consumption (binge drinking can precipitate attacks in those susceptible)
- High purine intake
- Drugs
Non-modifiable risk factors for gout
- Chronic kidney disease
- Male gender
- Age
- Genetics, family hx
What is hyperuricemia and how can it occur?
- Definition = serum uric acid > 480 umol/L in males or > 420 umol/L in females
- Etiology = overproduction and/or underexcretion
How is uric acid produced?
- Dietary intake, breakdown of tissue nucleic acids, and de novo synthesis => purines (guanine, adenine)
- Degradation of purines => uric acid
Do the majority of gout px have uric acid overproduction or underexcretion?
Underexcretion
What can cause uric acid overproduction?
- Diet
- Tissue/cell breakdown
- Metabolic derangement
What can cause uric acid underexcretion?
Renal abnormalities (67% of uric acid excreted by kidneys)
Describe renal excretion of uric acid
- 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
Factors altering renal excretion of uric acid
- 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)
What is monosodium urate (MSU)?
- 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)
Pathophysiology of gout
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
Clinical characteristics of acute gouty arthritis
- 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
Joints affected in gout
- Most common = toe, instep, ankle
- Medium prevalence = heel, knee, wrist
- Low prevalence = finger, elbow
Precipitating factors of gout
- Stress or trauma at the joint
- Alcohol (binge drinking)
- Infection, surgery
- Rapid lowering of serum uric acid
- Drugs that increase uric acid
Diagnosis of acute gout
Demonstration of sodium urate crystals in affected joint (take a sample of the fluid from the affected joint and analyze for sodium urate crystals)
What are intercritical periods?
- 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
Chronic complications of gout
- Nephrolithiasis
- Gouty nephropathy (acute uric acid nephropathy or chronic urate nephropathy)
- Tophi formation
What is chronic tophaceous gout?
- 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
Gout tx goals
- 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
Gout management approach
- 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
Pharm options for acute gouty arthritis and prophylactic therapy
- 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
Non-pharms for gout
- 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
NSAIDs for gout
- 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)