2. Drug therapy of gout - overview
ā¢ what is gout?
ā¢ what happens to patients with gout & why?
ā¢ what drugs are available for managing gout?
ā¢ how are those drugs used?
3. Drug therapy of gout
We have excellent drugs for managing gout
The drugs used in treating gout make sense!
6. Case presentation
ā¢ 55 y/o male
ā¢ 12 hours āpain in my big toe & ankleā
ā¢ went to bed last night feeling fine
ā¢ felt as if had broken toe this morning
ā¢ PMH of similar problems in right ankle & left
wrist
7. Case presentation
ā¢ can barely walk (due to pain)
ā¢ right elbow swollen
ā¢ exam shows left first MTP joint & left ankle
to be red, swollen & tender to touch
ā¢ right elbow also swollen
8. Case presentation
ā¢ lab studies
ļ¼serum uric acid = 11.5 mg/dl
ļ¼24-hour uric acid excretion = 300 mg
ā¢ left foot X-rays show bony erosion with
overhanging edge, medial side of first
metatarsal head
32. Classifying hyperuricemia
ā¢ serum uric acid level
ā¢ urine uric acid excretion (24-hour)
serum uric acid
urine uric acid
overproduction
high
high
underexcretion
high
normal/low
33. Gout - problems
ā¢ excessive total body levels of uric acid
ā¢ deposition of monosodium urate crystals in
joints & other tissues
ā¢ crystal-induced inflammation
34. Drug therapy of gout
What Drugs Are Available
For Treating Gout?
41. Colchicine
ā¢ āonly effective in gouty arthritisā
ā¢ not an analgesic
ā¢ does not affect renal excretion of uric acid
ā¢ does not alter plasma solubility of uric acid
ā¢ neither raises nor lowers serum uric acid
42. Colchicine
ā¢ mechanism of action poorly understood
ā¢ reduces inflammatory response to deposited
crystals
ā¢ diminishes PMN phagocytosis of crystals
ā¢ blocks cellular response to deposited
crystals
51. Gout - urate-lowering therapy
ā¢ prevents arthritis, tophi & stones by lowering
total body pool of uric acid
ā¢ not indicated after first attack
ā¢ initiation of therapy can worsen or bring on
acute gouty arthritis
ā¢ no role to play in managing acute gout
52. Drug therapy of gout
Drugs That Block
Production of Uric Acid
57. Allopurinol effects
Effect of Allopurinol on Total Serum Levels of
Xanthine + Hypoxanthine
Normal
0.15
mg/dl
Allopurinol
0.35
mg/dl
saturation level of xanthine & hypoxanthine > 7 mg/dl
60. Allopurinol
ā¢ 90% absorption from the gut
ā¢ metabolized to oxypurinol
ā¢ once daily dosing
ā¢ lowers serum uric acid levels
ā¢ lowers urine uric acid levels
ā¢ side effects rare, but potentially lethal
61. Allopurinol - usage indications
ā¢ management of hyperuricemia of gout
ā¢ management of hyperuricemia associated
with chemotherapy
ā¢ prevention of recurrent calcium oxalate
kidney stones
62. Allopurinol ā black box warning
THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT
RECOMMENDED FOR THE TREATMENT OF
ASYMPTOMATIC HYPERURICEMIA
ALLOPURINOL SHOULD BE DISCONTINUED AT
THE FIRST APPEARANCE OF SKIN RASH OR
OTHER SIGNS OF AN ALLERGIC REACTION
63. Allopurinol - common reactions
ā¢ diarrhea, nausea, abnormal liver tests
ā¢ acute attacks of gout
ā¢ rash
66. Allopurinol hypersensitivity
ā¢ extremely serious problem
ā¢ prompt recognition required
ā¢ first sign usually skin rash
ā¢ more common with impaired renal function
ā¢ progression to toxic epidermal necrolysis &
death
67. Febuxostat
ā¢ recently approved by FDA (not on market)
ā¢ oral xanthine oxidase inhibitor
ā¢ chemically distinct from allopurinol
ā¢ 94% of patients reached urate < 6.0 mg/dl
ā¢ minimal adverse events
ā¢ can be used in patients with renal disease
68. PEG-uricase
ā¢ investigational drug
ā¢ PEG-conjugate of recombinant porcine
uricase
ā¢ treatment-resistant gout
ā¢ uricase speeds resolution of tophi
ā¢ further research needed
69. Drug therapy of gout
Drugs That Enhance
Excretion of Uric Acid
72. Uricosuric therapy
ā¢ moderately effective
ā¢ increases risk of nephrolithiasis
ā¢ not used in patients with renal disease
ā¢ frequent, but mild, side effects
ā¢ some drugs reduce efficacy (e.g., aspirin)
