Term
| clinical spectrum of gout |
|
Definition
Hyperuricemia (>6.8 mg/dL) - 50% have it
Recurrent acute gouty arthritis attacks
Monosodium urate crystals in synovial fluid leukocytes
Deposits of monosodium urate crystals (tophi) in tissues in and around joints
Interstitial renal disease
Uric acid nephrolithiasis |
|
|
Term
| what is a goal level of uric acid for gout treatment? |
|
Definition
|
|
Term
| what is a central feature of gout? |
|
Definition
hyperuricemia (>6.8 mg/dl)
(not all pts have it) |
|
|
Term
| what stage pts don't have to be treated? |
|
Definition
| asymptomatic hyperuricemia (elevated serum urae with no clinical gout, silent tissue crystal deposition begins), may never develop a gout attack |
|
|
Term
| what is a reason for advanced gout? |
|
Definition
| uncontrolled hyperuriceia |
|
|
Term
| what ar intercritical segments? |
|
Definition
intervals between gout flares
(asymptomatic periods) |
|
|
Term
| what are common gout comorbidities? |
|
Definition
| HTN, CKD, insulin resistance |
|
|
Term
| what is peak incidence of gout? |
|
Definition
|
|
Term
| in which genger gout is more common? |
|
Definition
male (7-9xW)
postmenopausal women: W=M |
|
|
Term
| what lab value may correlate with uric acid level? |
|
Definition
|
|
Term
| wht can lead to increased level of uric acid? |
|
Definition
|
|
Term
|
Definition
end product of purin degradation
waste product |
|
|
Term
| why only humans develop gout? |
|
Definition
| they are lack of uricase (enzyme that convert uric acid to allantoin) |
|
|
Term
|
Definition
1. dietary purines
2. Conversion of tissue nucleic acid to purine nucleotides
3. De novo synthesis of purine bases |
|
|
Term
| how much UA average human produces a day? |
|
Definition
|
|
Term
| how much UA a person gets from diet daily? |
|
Definition
|
|
Term
|
Definition
10-20% of pts with gout
people who produces more UA than excrete
Abnormalities in purine metabolism enzyme regulation overproduction
Increased breakdown of tissue nucleic acids & excessive rates of cell turnover
Myeloproliferative/lymphoproliferative disorders
Polycythemia vera
Psoriasis
Some types of anemias
(Cytotoxic meds to treat the above) |
|
|
Term
| what percent of gout population ate underexcretors? |
|
Definition
|
|
Term
| what is common practice to identify pt status? |
|
Definition
Regular diet
> 1000mg in urine per 24 hrs - overproduction
< 1000mg in urine - ‘normal’
< 800mg in urine - underexcretor |
|
|
Term
|
Definition
deposits of monosodium urate crystals in soft tissues (can be on upper and lower extremities)
takes 10+ years to develop |
|
|
Term
| what are complications of tophaceous gout? |
|
Definition
soft tissue damage
deformity
joint destruction
nerve compression symptoms (carpal tonnel syndrome) |
|
|
Term
| in what population we can see atypical gout more often? |
|
Definition
|
|
Term
| what are sings of classic acute gout? |
|
Definition
monoarticular arthritis
frequently attack metatarsophalangeal joint (other joints on lower extremities are often involved)
fiver
with/without hyperuricemia
last 3-14 days |
|
|
Term
| what are renal effects of gout? |
|
Definition
nephrolithiasis
acute and chronic gouty nephropathy |
|
|
Term
| what is a definitive diagnosis for gout? |
|
Definition
aspirtion of synovial fluid from affected joint
ID negative birefringent monosodium urate crystals in sinovial fluid leukocytes |
|
|
Term
|
Definition
1. inflamatory monoarthritis
2. elevated uric acid level
3. response to colchicine
limits:
1. failure to recognise atypical gout;
2. serum UA level is normal 50% of the time |
|
|
Term
| what are two types of gouty nephrpathy? |
|
Definition
acute - result of blockage of urine outflow secondary to massive UA crystal preciptation;
chronic - long-term urate crystal deposition |
|
|
Term
| what are most common sites of tophaceous gout? |
|
Definition
| great toe, helix of ear, Achiles tendon, knees, wrists,hands |
|
|
Term
| what are rear sites of tophaceous gout? |
|
Definition
|
|
Term
|
Definition
1. Terminate acute attack
2. Prevent recurrent attacks
3. Prevent complications
4. Prevent or reverse commonly associated illnesses
Obesity, hypertriglyceridemia, HTN |
|
|
Term
| What agents are used in acute gout? |
|
Definition
NSAIDs,
colchicine,
corticostroids |
|
|
Term
| what agents are considerred a mainstay of therapy for acute gout attack? |
|
Definition
|
|
Term
| why NSAIds are mainstay of therapy for acute gout attack? |
|
Definition
| excellent efficacy and minimal toxicity (when used short term) |
|
|
Term
| What NSAIDs are FDA-approved for acute gout? |
|
Definition
Indomethacin (Indocin)
Naproxen (Naprosyn)
Sulindac (Clinoril)
efficacy is equal btwn gents |
|
|
Term
| What NSAID is not approved by FDA, but often used for acute gout attack? |
|
Definition
|
|
Term
| Most important for therapeutic success when treating acute gout with NSAIDs? |
|
Definition
Initiate at onset of symptoms
Initiate at maximum doses, continue 24 hrs after resolution, taper quickly over 2-3 days
Symptoms should resolve in 3-5 days. |
|
|
Term
| Indomethacin dosing for acute gout |
|
Definition
| 25-50 MG po qid X 3 DAYS, THEN TAPER TO bid X 4-7 DAYS |
|
|
Term
| naproxen dosing for acute gout |
|
Definition
| 500mg po BID x 3 days, then 250mg-500mg po daily x 4-7 days |
|
|
Term
| sulindac dosing for acute gout |
|
Definition
|
|
Term
|
Definition
GI (gastritis, bleeding, perforation)
Renal (necrosis, ↓CrCl)
CV (Na & fluid retention, ↑BP)
CNS (impaired cognition, HA, dizziness) |
|
|
Term
| NSAIDs should be usedwith cautions in hystory of |
|
Definition
PUD
CHF
Uncontrolled HTN
Renal insufficiency
CAD
Anticoagulants |
|
|
Term
| NSAIDs contraindicated in |
|
Definition
Active PUD
Active bleeding
Uncompensated CHF
Severe renal impairment
Hypersens. to ASA or any NSAID |
|
|
Term
| when colchicine can be used for acute gout? |
|
Definition
| CI, intolerance or unresponsiveness to NSAIDs |
|
|
Term
|
Definition
antimitotic agent:
Prevents the activation, degranulation, and migration of neutrophils thought to mediate some gout symptoms |
|
|
Term
|
Definition
| must initiate within 48 hours of symptoms |
|
|
Term
|
Definition
GI adverse events
Dose-dependent N/V/D
Neutropenia, axonal neuromyopathy |
|
|
Term
| In what dosage form colchicne is available in th USA? |
|
Definition
| PO only, tablets - 0.6 mg |
|
|
Term
|
Definition
| Renal or hepatic impairment + P-gp or strong CYP3A4 inhibitors life-threatening or fatal colchicine toxicity |
|
|
Term
| Indications for CCS in gout attack |
|
Definition
CI, intolerance, or unresponsive to NSAIDs & colchicine
Polyarticular involvement may benefit |
|
|
Term
| dosing for CCS in acute gout |
|
Definition
Oral: 30-60mg prednisone-equivalent daily x 3-5 days, then taper in 5mg increments over 10-14 days until d/c
Taper necessary to prevent rebound flare-up
IM: triamcinolone x 1 dose; methylprednisolone x 1-2 days |
|
|
Term
| what CCS can be given as intraarticular injection? |
|
Definition
|
|
Term
| why long-term use of CCS should be avoided? |
|
Definition
| Osteoporosis, HPA suppression, cataracts, muscle deconditioning |
|
|
Term
| what should be closely monitor during treatment with CCS? |
|
Definition
| GI problems, bleeding disorders, CV disease, psychiatric disorders |
|
|
Term
| when to start gout prophylaxis? |
|
Definition
6-8 weeks after resolution of acute gout attack
Nevr during the attack |
|
|
Term
| when prophylaxis sould not be started? |
|
Definition
Mild first episode and responded to treatment
Serum urate minimally elevated or normal
24hr urinary uric acid excretion <1000mg with regular diet |
|
|
Term
| when prophylaxis is recommended? |
|
Definition
Severe attack
Complicated course of uric acid nephrolithiasis
Serum urate > 10 mg/dL
24 hr urinary uric acid excretion > 1000mg
Tophi are present |
|
|
Term
|
Definition
< 6 mg/dl
ideally < 5 mg/dl |
|
|
Term
| what agents can be used for gout prophylaxis? |
|
Definition
Colchicine
Xanthine Oxidase Inhibitors
Allopurinol (Zyloprim)
Febuxostat (Uloric)
Uricosurics
Probenecid
Sulfinpyrazone |
|
|
Term
| what agents can be used for underexcreters only? |
|
Definition
Uricosurics
Probenecid
Sulfinpyrazone |
|
|
Term
| what agent can be used for acte gout and prophylaxis? |
|
Definition
|
|
Term
| colchicine can be used for prophylaxis in what age group? |
|
Definition
| in 16 years of age or older |
|
|
Term
| What dose of colchicine can be use for prophylaxis? |
|
Definition
0.6 mg once or twice daily,
max dose 1.2 mg/day |
|
|
Term
| colchicine for gout prophylaxis is best for what patients? |
|
Definition
For patients with
No evidence of tophi
Normal or slightly elevated serum urate |
|
|
Term
| when we can stop prophylaxis with colchicine? |
|
Definition
Serum urate within normal range AND
Symptom-free x 1 year |
|
|
Term
| what agents and for how long can be used together wih colchicine for gout prophylaxis? |
|
Definition
| NSAIDS and/or any urate lowering agents for first 6 months |
|
|
Term
True/False
Resistance and tolerance to colchicine don't develop |
|
Definition
|
|
Term
| What agent is efficacious for underexcreters and overproducers? |
|
Definition
Allopurinol (Zyloprim)
Febuxostat (Uloric) |
|
|
Term
| What agent is most widely prescribed for gout prophylaxis? |
|
Definition
|
|
Term
| how does allopurinol lowers UA? |
|
Definition
|
|
Term
| What other labeled indications for allopurinol? |
|
Definition
| chemotherapy causing ↑uric acid, management of recurrent calcium oxalate calculi |
|
|
Term
True/False
Allopurinol promotes shrinkage of tophi? |
|
Definition
|
|
Term
|
Definition
| Active metabolite of allopurinol |
|
|
Term
| Why allopurinol can be dosed once daily? |
|
Definition
| due to active metabolite oxypurinol |
|
|
Term
|
Definition
Start: 100mg/day; ↑100mg/day q week
Available as 100mg, 300mg tablets
Maintenance dose: 100-300mg/day
can go higher to reach the goal for UA <6 mg/dl if no toxicity
Max: 800mg/day |
|
|
Term
| What is a os of allopurinol for tophaceous gout? |
|
Definition
|
|
Term
| What are AEs of allopurinol? |
|
Definition
Mild AEs
Skin rash, leukopenia, GI problems, HA, urticaria
Severe AEs
“allopurinol hypersensivity syndrome”
Hepatitis, interstitial nephritis, eosinophilia |
|
|
Term
| what percent of patients can't tolerate allopurinol? |
|
Definition
|
|
Term
| how allopurinol can interat with warfarin? |
|
Definition
| allopurinol will enhance warfarin anticoagulant effect |
|
|
Term
| What are advantages febuxostat over allopurinol? |
|
Definition
Not reported to cause hypersensitivity rxns
Dosage titration less complex
Once daily
No dosage adjustment with mild-mod renal impairment
Caution: < 30mL/min |
|
|
Term
| What are disadvantages febuxostat comparing to allopurinol? |
|
Definition
Limited labeled indications
CI: treatment with xanthine oxidase substrates (azathioprine)
Allopurinol has warning
↑CV thromboembolic events?
Possible ↑LFTs
Monitor at 2&4 months |
|
|
Term
| What are AEs of febuxostat? |
|
Definition
| Nausea, arthralgia, rash, ↑transaminases (6%) |
|
|
Term
|
Definition
| start at 40 mg once daily, ↑ to 80mg if serum uric acid not < 6 mg/dL |
|
|
Term
| Is 80 mg of febuxostat more effective than 300 mg allopurinol? |
|
Definition
|
|
Term
| Used only in DOCUMENTED underexcretion |
|
Definition
| uricosurics: probenecid and sulfinpyrazole |
|
|
Term
| Why probenecid is used for commonly than sulfinpyrazole? |
|
Definition
| less SEs, better tolerated |
|
|
Term
| What is MOA of uricosurics? |
|
Definition
| ↑ renal clearance by inhibiting postsecretory reabsorption of uric acid |
|
|
Term
| what are major SEs of uricosrics? |
|
Definition
| GI irritation, rash, hypersensitivity, gouty flare, stone formation |
|
|
Term
| What are DDIs of uricosurics? |
|
Definition
Salicylates interfere with mechanism - treatment failure
↑plasma conc. of penicillins, cephalosporins, sulfonamides, indomethacin |
|
|
Term
|
Definition
Crcl < 50 ml/min
overproducers
renal calculi history |
|
|
Term
| What is a treatment of choice for refractory gout? |
|
Definition
|
|
Term
| What is pegloticase (Krystexxa)? |
|
Definition
| PEGylated uric acid specific enzyme |
|
|
Term
|
Definition
| 8mg given as an IV infusion over >120 minutes every 2 weeks (optimal tx duration has not been established). |
|
|
Term
| what is a contraindicatin for pegloticase? |
|
Definition
|
|
Term
| Common SEs of pegloticase |
|
Definition
Anaphylaxis/Infusion Reactions
Gout Flares - more common in first 3 months
Nausea/Vomiting
Contusion or ecchymosis
Constipation
Chest Pain
Immunogenicity |
|
|
Term
Need to D/C pegloticase during gout flares
True/False |
|
Definition
|
|
Term
| How to avoid anaphylaxis with pagloticase? |
|
Definition
| pre-medicate with antihistamines/corticosteroids; monitor closely and slow infusion down or stop if occurs |
|
|
Term
| When anaphylaxis or infusion reaction is seen with pagloticase? |
|
Definition
|
|
Term
no dose reduction in renal insufficincy while taking pegloticase
True/False |
|
Definition
|
|
Term
| What should pts taking pegloticase be educated on? |
|
Definition
Anaphylaxis/Infusion rxns can occur at any time during therapy
Stress importance of adherence to prophylactic medication
Educate on s/s of anaphylaxis
Wheezing, rash, peri-oral or lingual edema, urticaria, hemodynamic instability
Do not stop if patient experiences gout flares. |
|
|
Term
| What criteria patient should meet to start Krystexxa? |
|
Definition
Baseline serum uric acid of 8+ mg/dL
Symptomatic gout with 3+ gout flares in the previous 18 months
Or at least 1 gout tophus or gouty arthritis
Self-reported contraindication to allopurinol
Or medical history of failure to normalize uric acid (<6 mg/dL) with 3+ months of allopurinol treatment at the maximum dose |
|
|
Term
| Place of Krystexxa in therapy |
|
Definition
a bridging therapy
~ 6 month duration in severe treatment refractory gout
Once urate levels have been controlled, other antihyperuricemic medications can be restarted to maintain urate balance |
|
|
Term
| What other agents can be used for gout? |
|
Definition
|
|
Term
| What agent does not cause acute gout attack? |
|
Definition
|
|
Term
| What is MOA of fenofibrate in gout? |
|
Definition
| Ancillary benefit by ↓ clearance of hypoxanthine and xanthine - sustained reduction in serum rate |
|
|
Term
| What MOA of losartan in gout treatment? |
|
Definition
Inhibits renal tubular reabsorption of uric acid - ↑ urinary excretion
Alkanizes urine - ↓ stone formation |
|
|
Term
Other ARBs can be used for gout treatment
True/False |
|
Definition
False.
It is not a class effect. |
|
|
Term
| What lifestyle mofifications are recommended for patients with gout? |
|
Definition
Decrease dietary intake
High saturated fats
Red meats/shell fish
Alcohol (beer>spirits>wine)
High fructose corn syrup
Weight loss
Joint rest x 1-2 days
Local application of ice |
|
|
Term
|
Definition
Baseline
Renal & hepatic function, CBC, electrolytes
Prophylaxis treatment
Recheck baseline labs q 6-12 months
Serum uric acids levels monitored during dose titration phase until < 6 mg/dL
Because ↑ comorbities evaluate for CV disease
Look for correctable causes
Diuretics, niacin, obesity, malignancy, alcohol abuse |
|
|
