Term
Allopurinol (Zyloprim®)
Use, Mechanism of Action |
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Definition
•Chronic gout treatment
•Hypoxanthine analog
•Inhibits xanthineoxidase, decreasing production of uric acid |
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Term
Allopurinol (Zyloprim®)
Adverse Effects |
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Definition
•Rash
–Rash rarely precedes Stevens-Johnson or toxicity syndrome, so drug should be discontinued if rash occurs
•Toxicity syndrome
–2 - 4 weeks after initiating therapy
Rash, fever, hepatitis, renal failure |
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Term
Febuxostat (Uloric®)
Use, Mechanism of Action |
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Definition
•For symptomatic hyperuricemia only
•Inhibits xanthineoxidase
•Studies: faster & more effective than allopurinol at reducing serum uric acid below target levels |
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Term
Febuxostat (Uloric®)
Adverse Effects, Interactions |
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Definition
•Elevated liver enzymes
•Gout flares in early therapy
•Increased rate of cardiovascular events and deaths (??)
Interactions similar to allopurinol |
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Term
Pegloticase (Krystexxa®)
Therapeutic Use |
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Definition
•For chronic therapy of treatment-failure gout; symptomatic hyperuricemia only!
•Given IV every 2 weeks |
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Term
Pegloticase(Krystexxa®)
Mechanism of Action |
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Definition
•Recombinant uricase enzyme
•Pegylated for longer duration of action
•Breaks down uric acid to allantoin (easily excreted) |
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Term
Pegloticase (Krystexxa®)
Adverse Effects |
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Definition
•Allergic reaction in 25% of patients (urticaria, pruritis, etc.), even with pretreatment with antihistamine & glucocorticoid prior to administration (do pretreat!). Anaphylaxis in 5%.
–Antibody formation to drug; correlates with allergic reaction. |
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Term
Colchicine
Use, Mechanism of Action |
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Definition
•For acute gout attack, or chronic therapy
•Inhibits microtubule formation, resulting in:
–Inhibition of mitosis in rapidly dividing cells
–Inhibition of chemotaxis and secretion of inflammatory mediators |
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Term
Colchicine
Adverse Effects |
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Definition
•GI upset
•Alopecia
•Bone marrow suppression
•Myopathy
•Renal toxicity |
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Term
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Definition
•Probenecid
•Sulfinpyrazone |
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Term
Uricosuric Agents
Adverse Effects |
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Definition
•Hypersensitivity
•GI upset
•Renal stones
•Gout flares in early therapy
•Cytopenias with sulfinpyrazone - CBC is monitored |
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Term
Uricosuric Agents
Drug Interactions |
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Definition
•Probenecid decreases renal secretion of organic acids (penicillins, NSAIDs)
–Results in increased blood levels
•Salicylates decrease effectiveness of uricosuric drugs |
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Term
Hydroxyurea
Therapeutic Uses
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Definition
•Cancer chemotherapy drug – used to reduce cell numbers in AML or the blastic phase of CML
Used as chronic therapy for sickle cell disease in which a person has frequent/severe episodes of pain. |
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Term
Hydroxyurea
Mechanism of Action: Cancer |
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Definition
•Inhibits ribonucleotidereductase (converts ribonucleotides to deoxyribonucleotidetriphosphates)
Causes arrest in S phase |
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Term
Hydroxyurea
Mechanism of Action: SCD |
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Definition
•Problem in SCD: mutated hemoglobin (HbS)
–In deoxy state, HbS forms gel-like substance with Hb crystals
–Sickling of red cells occurs; these cells are more able to form clots, undergo hemolysis
•Sickle cells express surface proteins that induce inflammatory responses in vascular endothelium
–Leukocytes are recruited, sickle cells adhere, clots form |
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Term
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Definition
Induces production of HbF, increases total Hb and HbF levels (up to 20% of total)
Decreases leukocyte production in bone marrow, decreasing neutrophil adherence to vascular endothelium |
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Term
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Definition
NSAIDS
indomethacin, naproxen,sulindac,celecoxib
NO effect on uric acids levels
DO NOT use aspirin--it ↓ renal uric acid excretion
GUCOCORTICOIDS
GIVEN W/ nsaids for several days
COCHICINE
anti-inflammatory |
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Term
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Definition
Life long drug therapy to keep uric acid levels donw & prevent attacks:
- dietary purine restriction
- xanthine oxidase inhibitor, colchicine or uricosuuric drug are given on a daily basis
- if failure tx w/ pegloticase
- during initiation, gout flare prophylaxis with NSAIDS or colchicine
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