Drugs for Gout Flashcards
What is the definition of hyperuricemia?
Hyperuricemia is defined as the condition in which the concentration of uric acid in the plasma is > 7 mg/dL
What are the two broad categories of causes of hyperuricemia?
Metabolic (10%)
Renal (90%)
What are the metabolic causes of hyperuricemia?
Primary:
Specific enzyme abnormalities
Secondary:
Increased purine biosynthesis, Certain blood disorders, chemotherapy, or radiation therapy
What are the renal causes of hyperuricemia?
Primary:
Kidney disease
Secondary: (the majority)
Long-term diuretic therapy
Toxemia of pregnancy
What are the drugs used to treat gout?
Colchicine Indomethacin Allopurinol probenicid Febuxostat Pegloticase
What are the therapeutic applications for gout?
Colchicine is only effective against gout.
It is used as a prophylactic agent against attacks of gout, or to terminate acute attacks. It can also be used in familial mediteranean fever
What is the MOA of colchicine?
Colchicine depolimerizes microtubules
What are some important side effects of Colchicine?
G.I. disturbances (acute) Blood dyscrasias (chronic)
What is the MOA of Indomethacin?
Indomethacin is a cyclooxygenase inhibitor that functions as an analgesic, antipyretic, and inhibitor of leukocyte motility.
Is indomethacin better for acute attacks or chronic management of gout?
Indomethacin is better for treatment of acute attacks of gout.
What should be taken with Indomethacin to improve its absorption?
antacids
What ADEs are associated with Indomethacin?
GI: N/V , ulcers
CNS: severe frontal headache
Hematopoietic disorders
Antagonizes Furosemide and HCTZ
What is the MOA of Allopurinol?
Competitive inhibitor of Xanthine oxidase
What is Allopurinol metabolized to?
Oxypurinol (a non-competitive inhibitor of xanthine oxidase)
What are the therapeutic effects of allopurinol?
- Reduces plasma levels and urinary excretion of Uric acid
- Increases Xanthine and oxyxanthine excretion
- facilitates dissolution of uric acid crystals in the joints
- prevents formation of kidney stones
In what clinical situations should allopurinol be prescribed?
Should be used for the prophylactic treatment of primary hyperuricemia due to enzyme abnormalities or Secondary hyperuricemia due to hematologic disorders and chemotherapy.
What are some adverse effects associated with allopurinol?
- increased acute gout
- Hypersensitivity (dermatitis)
- Liver toxicity
- contraindicated with 6-MP, ampicillin, and related antibioltics.
What is the MOA of febuxostat?
potent inhibitor of both the oxidized and reduced forms of xanthine oxidase that is not structurally related to allopurinol
Which is better allopurinol or febuxostat?
Febuxostat is more potent than allopurinol and has less adverse effects.
What medical conditions might limit the use of allopurinol but not febuxostat?
Renal impairment
What are the ADEs associated with febusostat?
Transaminase elevation
How does the kidney handle uric acid?
- Filtration then reabsorption in PCT
2. Secreted then partially reabsorbed
What is the MOA of probenacid?
Probenacid inhibits the transport of organic anions across epithelial barriers (especially the PCT brush border). Prevents the renal reabsorption of uric acid leading to lower UA levels in the the blood and the dissolution of uric acid crystals in the joints.
What ADEs are associated with probenacid?
Salicylates inhibit uricosuric action of probenacid.
