Pharm - Gout Flashcards
Defne hyperuricemia
- not gout but increases risk for gout
- necessary for development of urate crystal deposition
- elevated uric acid in the blood
- uric acid level > 6 mg/dL
Define Gout
- Arthritic condition resulting from deposition of monosodium urate (MSU) crystals in and/or around joints, bones, soft tissues following long-standing hyperuricemia
- A clinical syndrome
Define Tophus/tophi
- pathognomonic feature of gout
* Deposit of crystalline uric acid and other substances at surface of joint or in skin or cartilage
What food and drink should be avoided/limited to prevent gout
Avoid:
- BEER, alcohol overuse (>2/day men, >1/day women
- organ meets high in purines,
- high fructose corn syrup (soda, beverage, food)
Limit:
- beef, lamb, pork, seafood with high purine (sardines, shellfish)
- naturally sweetened fruit juice
- table sugar
- salt
What is goal of therapy when treating acute gout attack
Prompt and safe termination of pain and disability
What is the timeline for treating an acute gout attack
- Sudden in onset, severe debilitating pain with max intensity within 8-12 hrs
- Initiate treatment as soon as possible, preferably within several hours of sx onset
- Continue tx for duration of attack
- Continue tx until the pt has been sx free for 2-3 days
What factors should modify the selection of anti-inflammatory drug for acute gout attack tx
- Renal function
- CVD (HF and poorly controlled HTN)
- GI disease, including peptic ulcer disease
- Drug allergy
- Poorly controlled DM
Indications for us of glucocorticoid in the tx of acute gout attack
Mild to moderate pain, attack only affects one or a few small joints or 1-2 lrg joints
what is the amount of intra-articular glucocorticoid in the treat of acute gout attack based on?
The size of the joint
What can occur when oral glucocorticoid tx is withdrawn?
rebound gout attack
What is the role of NSAID in the tx of acute gout attack?
- Mild to moderate pain, attack only affects one or a few small joints or 1-2 lrg joints
- Good alternative to glucocorticoids esp if <60, no renal dz, no CVD, no active GI dz
Who should NOT receive NSAIDs for tx of acute gout attack (7)
- Hx of peptic ulcer dz (duodenal or gastric)
- Hx of GI bleeding
- Predisposed to gastritis
- Renal insufficiency (CrCl <60)
- Abnl heaptic fn
- Use anticoagulants
- Limit in elderly due to CNS effects
Duration of NSAID when tx acute gout attack
- Start within 12-24 hours of attack beginning
- Start at highest dose for 2-3 days, then decrease over approx. 2 weeks
- Continue for at least 48 hours after resolution of sx
Role of colchicine in tx of acute gout
- If pt has contraindication to NSAIDs (mod-severe chronic kidney dz, active peptic ulcer disease, or hx of NSAID intolerance)
- May abort attacks of gout if used as soon as pt perceives the first sign of an attack.
- May be an alternative to glucocorticoids or NSAIDs for flare tx if it has worked in past
What are the contraindications to colchicine
Concomitant use of a strong CYP3A4 inhibitor or a P-glycoprotein inhibitor if pt has renal or liver impairment
**Amiodarone, PPI, SSRI, CaCB, macrolides)
What is the dosing regimen for the treatment of colchicine for an acute gout attack
Day 1:
• 1.2 mg at first sign of flare, 1 hour later a single dose of 0.6 mg (max 1.8 within one hour) OR
• 0.6 mg TID on first day of flare (max total dose 1.8 mg on day 1)
• If already receiving prophylactic colchicine, resume prophylaxis dosing 12 hours after initial treatment (results in higher doses being administrated on day 1)
Day 2:
• 0.6 mg once or twice daily until flare resolves
What are the indications for uric acid lowering therapy (6)
- Tophaceous deposits in soft tissue or subchondral bone (IDed via clinical exam or imaging)
- Clinical or radiographic signs of chronic gouty joint disease (gouty arthropathy)
- Frequent gout attacks of acute gout arthritis (≥2 attacks/yr)
- Chronic kidney disease stage 2 or worse (CrCl <60 mL/min)
- Hx of uric acid renal stones
- Urinary uric acid excretion exceeding 1100 mg/day in men <25 or premenopausal woman (increased risk of uric acid stones)
What is the uric acid treatment target when using uric acid lowering tx?
< 6 ml/dL
What are the drugs of choice for the prevention of gout
1st line: Xanthine Oxidase inhibitor (XOI)
• Allopurinol (cheaper)
• Febuxostat (Uloric)
Second Line (XOI is contra-indicated or not tolerated)
• Probenecid (Benemid)
• Lesinurad (Zurampic)
• Alternative uricosuric agents
What is the risk for an acute gout attack when initiating uric acid lowering therapy
- Tx acutely lowers uric acid in blood, mobilizing urate cyrstals from body tissues and joints, precipitating a gout attack!
- Wait two weeks min after acute attack to start uric acid lowering therapy may reduce risk
What is the role of colchicine in acute gout prophylaxis
1st line for acute gout attack prophylaxis (0.6 mg once or twice daily)
• Note: 1st line prophylaxis is colchicine OR NSAID with PPI
What is MoA of colchicine
- anti-inflammatory.
- Reduces inflammatory response to deposited cyrstals by diminishing the ability of white blood cells to phagocytize crystals and blocks cellular response to deposited crystals.
- Inhibits polymerization of tubulin in microtubules, preventing ability of cell to move in body. Why have to initiate treatment early, before WBC reach the site of inflammation.
What is the duration of tx for acute gout prophylaxis when starting uric acid lowering agent?
- Continue if gout signs and sx persist
- If no signs or sx of gout:
• Continue for min 6 months OR
• Treat for 3 months after achieving target serum urate and no tophi detected on PE
• Treat for 6 months after achieving target serum urate if 1+ tophi detected on PE
What are the two xanthine oxidase inhibitors
- Allopurinol
- febuxostat
What is the MoA of xanthine oxidase inhibitors
prevents the conversion of hypoxanthine to uric acid
What is the starting dose of allopurinol in pts with adequate renal function?
100 mg/day
What patients are at highest risk for hypersensitivity to allopurinol?
- Han Chinese, Thai, Korean heritage who have a CrCl <60 mL/min
What testing is required for pts at high risk for allopurinol hypersensitivity?
HLA testing: HLA-B 5801
What are the three uricoseric agents?
- probenecid
- Lesinurad
- pegloticase
What is the uricoseric MoA of Probenecid and lesinurad
Increases renal excretion of uric acid by inhibiting anionic transport sites (URAT transporters) in the renal PCT
*Lesinurad also OAT4
Best candidate for probenecid therapy
- Younger, <60 yo
- Underexcreter of uric acid
- Good renal function CrCl > 60 mL/min
- No hx of kidney stones
- Do not require aspirin or diuretic therapy
Contraindications for probenecid therapy
- History of urolithiasis
- Indications of uric acid overproduction
- Renal fn <60 mL/min
- Might need high dose ASA or diuretic therapy
What is the major drug interaction with probenecid?
high dose ASA antagonizes the action of probenecid
What is the place in therapy for lesinurad
In combo with XOI in pts who have not achieved target serum uric acid levels with XOI alone
What gout drug should never be used as mono therapy?
Lesinurad
What is the MoA for pegloticase
- Modified version of uricase, an enzyme that catalyzes the oxidation of uric acid to allantoin which is water soluble and easily eliminated
- Lowers serum uric acid level to improve or reverse the course of severe, crippling gout
What is the major contraindication associated with pegloticase
Pts with G6PD deficiency
- Use by these pts = increased risk of hemolysis and methemoglobinemia
What are the two major ADR of colchicine
- diarrhea
- abd cramps
