Gout Flashcards
Treatment for acute gout
NSAIN/Naproxen po Colchicine po Prednisone po Methylprednisolone iv Triamcinolone acetonide intra-articular
Treatment for chronic gout
Allopurinol po
Probenecid po
Pegloticase iv
What is uric acid?
Product of purine metabolism
How is uric acid generated?
Xanthine oxidase converts hypoxanthine to xanthine then uric acid by the insertion of two carbonyl groups
What is the steady start concentration of uric acid
<6.0 mg/dl
What are tophi
Uric acid accumulation in soft tissue
Uric acid kidney stones
- Favoured by which pH
Acid urine
Lifestyle modicifations for gout
DIet
Reduce alcohol intake
NSAIDS
Class Action Kinetics ADRs Interactions
Class NSAID (non-selective), anti-inflammatory, analgesic, antipyretic
Action
Inhibit COX 1 and 2, reducing production of inflammatory prostaglandins. Helps to relieve severe pain from gout within hours to days
Kinetics
Well absorbed when taken orally (95%); renally excreted (95%); can be taken twice per day
ADRs: gastric upset, gastritis, ulceration, ARF; avoid in patients with “allergy” to aspirin; fluid retention and edema
Interactions
Reduce activity of antihypertensives; may increase risk of GI bleeding with warfarin
Colchicine Class Action Kinetics ADRs Interactions
Class
Antigout drug for both acute attacks and for prevention
Action
Not entirely clear; seems to reduce leukocyte migration, reduce phagocytosis, reduce inflammatory response induced by uric acid crystals
Kinetics
Well absorbed when taken orally; distributes rapidly to tissues, concentrated in leukocytes; metabolized partially in liver, then excreted in bile; half-life 10-20 h
ADRs
most commonly nausea, vomiting, diarrhea–these are usually dose-limiting
Interactions
Erythromycin and other macrolides may increase risk of toxicity
Allopurinol Class Action Kinetics ADRs Interactions
Class
Antigout drug, xanthine oxidase inhibitor
Action
By blocking the enzyme xanthine oxidase (with its own metabolite), leads to less uric acid produced, and more hypoxanthine and xanthine in both blood and urine; when begun, may need to give colchicine as well to prevent acute flare of gout; try to reduce uric acid to <6 mg/dL, but only succeeds in about 40% of patients
Kinetics
Well absorbed when taken orally; metabolized quickly to oxypurinol, half-life about 15 h; about 70% of dose excreted in urine as oxypurinol
ADRs
Hypersensitivity vasculitis, agranulocytosis, hepatic necrosis, TEN/Stevens Johnson syndrome; can precipitate an acute attack of gout
Interactions
Dramatic increase in toxicity of azathioprine and 6-MP; doses need to be reduced to 25-33% of normal
What is allopurinol metabolised to and by what
Alloxanthine by xanthine oxidase
Probenecid Class Action Kinetics ADRs Interactions
Class
Sulfonamide derivative, uricosuric agent, adjunct to Penicillin G treatment
Action
competitively inhibits the active reabsorption of uric acid at the PCT,thereby increasing urinary excretion of uric acid (uricosuric effect); also competitively inhibits the active tubular secretion of Pen and other weak acid antibiotics, thereby leading to higher serum levels
Kinetics
Well absorbed when taken orally; cleared by both liver metabolism and urinary excretion; usually given bid; half-life 4-17 h
ADRs
Contraindicated with previous allergy, or those with uric acid kidney stones; risk of aplastic anemia, hepatic necrosis, allergy; can precipitate an acute attack of gout!!
Interactions
may significantly slow the renal clearance of drugs such as Pen G, cephalosporins, MTX (methotrexate)
Peglocticase Class Action Kinetics ADRs Interactions
Class
A pegylated urate oxidase enzyme (recombinant mammalian enzyme, produced in E. coli) approved by FDA for IV treatment of chronic severe symptomatic gout in adults who have not responded to, or can’t tolerate, older and simpler treatments (and less expensive!)
Action
Uricase catalyzes oxidation of uric acid to allantoin, a metabolite that is inert, water soluble, and cleared by the kidney; a single injection produces maximal reduction in serum urate within 24 hours; For the endpoint of producing uric acid levels 80% of the time, success rates were 38-47% ( 8 mg q2weeks), 20-49% (8 mg q4weeks), 0% (placebo)
Kinetics
As an active enzyme, must be given IV; generally maintains serum uric acid <6 mg/dL for up to 12 days; must be given q2weeks
ADRs
Antibodies develop in 92% of patients; make drug less effective; occasionally (4/85 patients) can cause anaphylaxis; can precipitate acute attacks of gout; should receive an antihistamine and a corticosteroid prior to infusion; prophylaxis with an NSAID or colchicine recommended for 6 months
Warnings
Should be given in a healthcare setting by providers capable of managing anaphylaxis
