Gout Flashcards
For a case, do NOT choose treatment unless a gout attack has occurred
Uric acid comes from breaking down __________
purines, often in foods and medications
Gout is a type of arthritis caused by _______
a buildup of Uric acid crystals, primarily in the joints.
Uric acid crystallization
Symptoms of Gout include:
Severe pain, swelling and redness in joints.
Sudden onset
Uric acid is produced as an end product of ________
purine metabolism
Uric acid is mainly excreted, _____
renally (primarily)
a normal serum UA level is ______________ in females
a normal serum UA level is ______________ in males
- 2-6.5 mg/dL
- 3.5-7.2 mg/dL
Uric acid can crystallize in the joints called __________. This results in a severe painful gout attack with burning and swelling of the affected joint.
If left untreated, the attacks ____________
tophi
can occur repeatedly and damage the joints, tendons and other tissues.
Gout typically occurs in one joint, most often the _______________
metatarsophalangeal joint (MTP, the big toe)
Risk factors for Gout include:
-male sex
- obesity
- EXCESSIVE ALCOHOL (particularly beer)
- hypertension
- chronic kidney disease
- lead intoxication
- advanced age
- using medications that increase UA
Drugs that increase Uric Acid include:
- aspirin, lower doses
- Calcineurin inhibitors (tacrolimus & cyclosporine)
- Diuretics (loops & thiazides)
- Niacin
- Pyrazinamide- “RIP” - regimen for Tuberculosis
- select chemotherapy (with tumor lysis syndrome)
- select pancreatic enzyme products
Niacin has a Contraindication for severe Gout but when it is controlled __
can use it.
But what Gout isn’t severe.
So we wouldn’t want to use during a Gout attack
Changing the diet can lower risk of Gout. Foods to avoid include: _________
Limit fruit juices, table sugar, sweetened drinks and desserts, salt, beef, lamb, pork, and seafood with high purine content (sardines, SHELLFISH)
Encourage a healthy diet: low-fat dairy products, vegetables and HYDRATION.
ORGAN MEATS, high-fructose corn syrup, alcohol
Asymptomatic hyperuricemia is NOT ______
treated with drugs
Gout Treatment Basics
-
-
2) Treat chronically to prevent future attacks (prevention of future attacks)
-
-
-
1)
- Colchicine
- Steroids
-NSAIDs
2)
- Xanthine oxidase inhibitor (XOI): allopurinol (preferred) or febuxostat
*** acute Tx needed when starting to prevent a flare
3)
-add on probenecid or lesinurad to daily XOI
- replace the XOI with IV pegloticase (Krystexxa)
The prophylactic drugs are used to lower (UA) Uric acid levels, with a goal UA level of______________
less than < 6mg/dL
An acute gout flare can occur when ___________
an XOI is started, so give initially with colchicine or an NSAID
The enzyme Uricase, is responsible for _____
the conversion of uric acid to Allantoin
The enzyme Xanthine oxidase is responsible for________
the conversion of Hypoxanthine —–> Xanthine &
Xanthine —-> Uric acid
(TLS)
Tumor Lysis Syndrome
(TLS) Tumor Lysis Syndrome:
is an acute, potentially life-threatening complication of some major types of chemotherapy. When cells are “lysed” open, purines are released into the blood and quickly converted to UA. This can cause acute gout and significant abnormalities, which can lead to renal failure, cardiac arrhythmias and potential death.
ULT
Urate Lowering Therapy
Celebrex
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Celecoxib
Class: NSAID, selective COX-2 inhibitor
Indications:
Dosing: 200mg PO BID, discontinue 2-3 days after attack resolved
MOA:
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Elitek
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Rasburicase
- urate oxidase enzyme
- ## used in the Tx of (TLS) Tumor Lysis Syndrome
- Contraindicated: in those with G6PD deficiency. DC immediately and permanently in any patient developing hemolysis.
Colcrys
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colchicine
Class: Antigout medication
Indications: Gout attack
Major substrate of CYP3A4 and P-gp
MOA: disrupts cytoskeletal functions by inhibiting B-tubulin polymerization into microtubules, preventing activation, degranulation, and migration of neutrophils associated with mediating some gout symptoms.
Dosing:
Tx: 1.2mg (two of the 0.6 tablets) followed by 0.6mg in 1 hour (do not exceed a total of 1.8mg in 1 hour or 2.4mg/day)
If CrCl < 30mL/min treatment dose is the same, but do not give again for 2 weeks.
Prophylaxis: 0.6mg once or twice daily
CrCl < 30mL/min: decrease to 0.3mg/day
Contraindications: Do Not use in combination with a P-gp or strong CYP3A4 inhibitor with renal and/or hepatic impairment
Warnings: Myelosuppression, neuromuscular toxicity (including rhabdomyolysis), if possible, do not use with cyclosporine, diltiazem, verapamil, gemfibrozil or statins as these drugs increase myopathy risk
Side Effects: Diarrhea, nausea, myopathy, neuropathy (dose-dependent), decreases vitamin B12.
Pearls/Notes:
-Start within 36 hours of symptom onset (for treatment)
wait 12 hours after a treatment dose before resuming prophylaxis dosing.
-Maintain adequate fluid intake.
-Do not use more than 3 tablets in an hour
-Do not use more than 4 tablets in 24 hours
-Do not take the second dose if you have stomach upset, nausea or diarrhea
Drug-Drug/Food interactions:
Fatal toxicity can occur if combined with strong CYP3A4 inhibitors, such as clarithromycin.
OR
strong inhibitor of P-gp such as cyclosporine
If used with a strong CYP3A4 inhibitor, dose is reduced and should not be repeated no earlier than 3 days.
If using a moderate CYP3A4 inhibitor, the maximum dose for an acute attack is 1.2mg
Mitigare
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colchicine
Class: Antigout medication
Indications: Gout attack
Major substrate of CYP3A4 and P-gp
MOA: disrupts cytoskeletal functions by inhibiting B-tubulin polymerization into microtubules, preventing activation, degranulation, and migration of neutrophils associated with mediating some gout symptoms.
Dosing:
Tx: 1.2mg (two of the 0.6 tablets) followed by 0.6mg in 1 hour (do not exceed a total of 1.8mg in 1 hour or 2.4mg/day)
If CrCl < 30mL/min treatment dose is the same, but do not give again for 2 weeks.
Prophylaxis: 0.6mg once or twice daily
CrCl < 30mL/min: decrease to 0.3mg/day
Contraindications: Do Not use in combination with a P-gp or strong CYP3A4 inhibitor with renal and/or hepatic impairment
Warnings: Myelosuppression, neuromuscular toxicity (including rhabdomyolysis), if possible, do not use with cyclosporine, diltiazem, verapamil, gemfibrozil or statins as these drugs increase myopathy risk
Side Effects: Diarrhea, nausea, myopathy, neuropathy (dose-dependent), decreases vitamin B12.
Pearls/Notes:
-Start within 36 hours of symptom onset (for treatment)
wait 12 hours after a treatment dose before resuming prophylaxis dosing.
-Maintain adequate fluid intake.
-Do not use more than 3 tablets in an hour
-Do not use more than 4 tablets in 24 hours
-Do not take the second dose if you have stomach upset, nausea or diarrhea
Drug-Drug/Food interactions:
Fatal toxicity can occur if combined with strong CYP3A4 inhibitors, such as clarithromycin.
OR
strong inhibitor of P-gp such as cyclosporine
If used with a strong CYP3A4 inhibitor, dose is reduced and should not be repeated no earlier than 3 days.
If using a moderate CYP3A4 inhibitor, the maximum dose for an acute attack is 1.2mg
Gloperba
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colchicine
Class: Antigout medication
Indications: Gout attack
Major substrate of CYP3A4 and P-gp
MOA: disrupts cytoskeletal functions by inhibiting B-tubulin polymerization into microtubules, preventing activation, degranulation, and migration of neutrophils associated with mediating some gout symptoms.
Dosing:
Tx: 1.2mg (two of the 0.6 tablets) followed by 0.6mg in 1 hour (do not exceed a total of 1.8mg in 1 hour or 2.4mg/day)
If CrCl < 30mL/min treatment dose is the same, but do not give again for 2 weeks.
Prophylaxis: 0.6mg once or twice daily
CrCl < 30mL/min: decrease to 0.3mg/day
Contraindications: Do Not use in combination with a P-gp or strong CYP3A4 inhibitor with renal and/or hepatic impairment
Warnings: Myelosuppression, neuromuscular toxicity (including rhabdomyolysis), if possible, do not use with cyclosporine, diltiazem, verapamil, gemfibrozil or statins as these drugs increase myopathy risk
Side Effects: Diarrhea, nausea, myopathy, neuropathy (dose-dependent), decreases vitamin B12.
Pearls/Notes:
-Start within 36 hours of symptom onset (for treatment)
wait 12 hours after a treatment dose before resuming prophylaxis dosing.
-Maintain adequate fluid intake.
-Do not use more than 3 tablets in an hour
-Do not use more than 4 tablets in 24 hours
-Do not take the second dose if you have stomach upset, nausea or diarrhea
Drug-Drug/Food interactions:
Fatal toxicity can occur if combined with strong CYP3A4 inhibitors, such as clarithromycin.
OR
strong inhibitor of P-gp such as cyclosporine
If used with a strong CYP3A4 inhibitor, dose is reduced and should not be repeated no earlier than 3 days.
If using a moderate CYP3A4 inhibitor, the maximum dose for an acute attack is 1.2mg
Indocin
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indomethacin
Class: NSAID
Indications: Approved for pain relief in acute gout attack
MOA:
Dosing: 50mg PO TID until attack resolved
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Monitoring:
Pearls/Notes: Avoid Use in severe renal disease (UA is renally cleared and patients with gout often have renal insufficiency) and CVD risk, bleeding (risk is lower with short duration of use)
Drug-Drug/Food interactions:
Aleve
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naproxen
Class: NSAIDs
Indications: Approved for Gout
MOA:
Dosing: 500mg PO BID until attack resolved
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Pearls/Notes: Avoid use in severe renal disease, cardiac disease, bleeding
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Sulindac
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Class:
Indications: Approved for gout
MOA:
Dosing: 200mg PO BID until attack resolved
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Intensol
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prednisone
Class: Corticosteroid
Indications: acute gout flare
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Rayos
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prednisone
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Millipred
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prednisolone
Medrol
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Dosing: oral dose pack
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Solu-Medrol
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Class:
Indications: Acute gout attack therapy
MOA:
Dosing: Intra-articular, if 1-2 large joints involved
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triamcinolone
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Zyloprim
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allopurinol
Class: Xanthine Oxidase Inhibitor
Indications: Chronic Urate Lowering therapy for prophylactic treatment in Gout
MOA: decreases uric acid production in the body by blocking the responsible enzyme Xanthine Oxidase for its production.
Dosing: Start at 100mg daily, then titrate slowly up until Uric acid is < 6mg/dL (doses > 300mg can be necessary and should be divided BID)
CrCl < or = 30mL/min: Start at 50mg daily, increase gradually up 300mg/day
Take after a meal (with food in stomach) to decrease nausea.
Contraindications:
Warnings: Hypersensitivity reactions including severe rash (SJS/TEN/DRESS); HLA-B*5801 testing prior to use if high risk (patients of Asian descent) and DO NOT use if +, hepatotoxicity.
Side Effects: rash, acute gout attacks, nausea, diarrhea, increased LFTs
Monitoring: CBC/LFTs/renal function
Pearls/Notes:
Higher doses are used for TLS
Take after a meal to reduce stomach upset (higher doses can be divided). Also drink plenty of fluids throughout the day.
**-due to the high rate of Gout attacks when beginning (ULT) Uate Lowering Therapy, use colchicine 0.6mg once or twice daily or an NSAID for the first 3-6 months.
Drug-Drug/Food interactions:
allopurinol increases the concentration of mercaptopurine, the active metabolite of azathioprine. Do not use either with allopurinol or decrease dose and monitor for toxicity.
**antacids can decrease allopurinol absorption.
Aloprim
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allopurinol
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Indications: Chronic Urate Lowering therapy for prophylactic treatment
MOA: decreases uric acid production in the body by blocking the responsible enzyme Xanthine Oxidase for its production.
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Uloric
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febuxostat
Class: Xanthine Oxidase Inhibitor
Indications: Chronic Urate Lowering therapy for prophylactic treatment
MOA: decreases uric acid production in the body by blocking the responsible enzyme Xanthine Oxidase for its production.
Dosing: 40-80mg daily (Max 120mg/day)
-Start at 40mg daily, may increase to 80mg daily if UA is NOT < 6mg/dL after 2 weeks.
-If CrCl < 30mL/min; (Max 40mg daily)
Boxed Warning: Increased risk of Cardiovascular death compared to allopurinol in patients with established CV disease; use should be limited to those who cannot tolerate allopurinol or if allopurinol is not effective
Contraindications: Do NOT USE with mercaptopurine or azathioprine
Warnings: Hepatotoxicity, possible MI or stroke, gout attack, hypersensitivity and serious skin reactions including SJS/TEN/DRESS
Side Effects: rash, nausea, increased LFTs,
Monitoring: LFTs
Pearls/Notes:
**-due to the high rate of Gout attacks when beginning (ULT) Uate Lowering Therapy, use colchicine 0.6mg once or twice daily or an NSAID for the first 3-6 months.
Drug-Drug/Food interactions:
increases the concentration of mercaptopurine, the active metabolite of azathioprine. Do not use febuxostat with either!!
Zurampic
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lesinurad
Class: Uricosuric
Indications: Chronic Urate (Uric acid) Lowering therapy for prophylactic treatment
MOA: inhibits reabsorption of Uric acid in the kidneys, increasing Uric acid secretion
Dosing: 200mg daily in the morning with a Xanthine oxidase inhibitor (allopurinol or febuxostat); if Xanthine oxidase inhibitor is stopped, then stop lesinurad.
-Only initiate if CrCl > or = to 45mL/min
- If CrCl < 30mL/min: Contraindicated
Boxed Warning: ONLY TO BE USED WITH Xanthine Oxidase Inhibitor, NOT FOR MONOTHERAPY. ACUTE RENAL FAILURE MORE COMMON IN MONOTHERAPY.
Contraindications:
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Pearls/Notes: Use only with a (XOI) Xanthine Oxidase inhibitor if UA goals not reached with XOI alone; keep hydrated.
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Duzallo
allopurinol/lesinurad
Probenecid
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Class: Uricosuric
Indications: Chronic Urate (Uric acid) Lowering therapy
MOA: inhibits reabsorption of uric acid in the kidneys, which increases Uric acid excretion
Dosing: Start 250mg BID, can increase to 2g/day
If CrCl < 30mL/min then AVOID USE
Contraindications: Do NOT use with aspirin therapy, blood dyscarsias, UA kidney stones (nephrolithiasis), children < 2 years, initiation in acute gout attack
Warnings: decreased effectiveness with CrCl < 30mL/min (ACR guidelines; do not use if CrCl < 50mL/min), DO NOT USE with G6PD deficiency
Side Effects: hypersensitivity reactions, hemolytic anemia
Monitoring:
Pearls/Notes:
-Can be used to increase beta-lactam levels by decreasing beta-lactam excretion. This will increase risk for adverse reactions associated with beta-lactams.
-May be useful in patients with good renal function or if taking medications that increase uric acid levels (loop diuretics)
Drug-Drug/Food interactions:
can decrease the renal clearance of other medications taken concurrently, including aspirin, methotrexate, theophylline, penicillin’s, etc.
Krystexxa
cra-stex-za
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pegloticase
(injection)
Class: Recombinant Uricase
Indications: Chronic Urate (Uric acid) Lowering therapy for prophylactic treatment of Gout
for refractory cases only
MOA: increasing conversion of Uric acid to Allantoin, which is excreted.
Dosing: 8mg IV every 2 weeks
Boxed Warnings: Anaphylactic reactions - monitor and premedicate with antihistamines and steroids, risk is highest if UA is > 6mg/dL; life-threatening hemolytic reactions and methemoglobinemia may occur with G6PD deficiency.
Contraindications: G6PD deficiency
Warnings: Acute Gout flares can occur upon initiation; an NSAID or colchicine should be given 1 week prior to infusion and continued for at least 6 months.
Side Effects: Antibody formation, gout flare, infusion reactions, nausea, bruising, urticaria, erythema
Monitoring:
Pearls/Notes: DO NOT USE in combination with allopurinol, febuxostat or probenecid (increased risk of anaphylaxis)
Drug-Drug/Food interactions:
Uric Acid Production and where Drug Treatment intervenes:
Adenosine —> Hypoxanthine —> Xanthine —> Uric acid
