Drug Excretion & Gout

Question 1

Probenecid [Benemid]

Answer 1

Uricosuric agent, p.o., lipid soluble acid, passive reabsorption, unless alkaline urine

MOA - Competitive inhibition of urate transport carriers (site B).

Low doses - inhibit secretion more than reabsorption, increase plasma urate

High doses - inhibits both secretion and reabsorption, reduce plasma urate

Side effects - GI disturbances,

Inc uric acid excretion-> kidney stones

Drug interactions - Aspirin dec tubular probenecid conc. Prevents action on urate.

Additive effects with sulfinpyrazone, antagonizes diuretics

Question 2

Sulfinpyrazone

Answer 2

Me2 - Probenecid - MOA and Use

High GI side effects, lower hypersensitivity

Antithrombotic properties (unk. mech.)

Question 3

Allopurinol

Answer 3

MOA - inhibition of xantine oxidase

Xantine isomer, metabolizes by enzyme to alloxantine - long lasting inhibitor of enzyme

USE - Chronic, tophagous gout

Indications - pts. producing large amt of urate, impaired renal function, hsr to uricosuric agents

Drug interactions

Azothiaprine, mercatopurine, dideoxyadenosie, warafin metabolism.

Activates 5-flurourcil.

Question 4

Febuxostat [uloric]

Answer 4

Gout medication

More specific inhibitor of xantine oxidase than allopurinol

reduced hypersensitivity, inc CV adverse effects

Question 5

Pegloticase [Krystexxa]

Answer 5

Mammalian recominbate uricase - pegylayted to reduce immunoreactivity

Infusion

Gout unresponsive to standard therapy

All mammals, except primates and man, have the enzyme uricase which oxidizes uric acid to alltoin, which is highly water soluble and easily excreted.

Rasburicase - recombinant uricase from yeast

Question 6

Colchicine

Answer 6

MOA - impairs chemotaxis and phagocytosis of leukocytes

Binding and interfering with activity of tubulin

Nausea and vomiting