1. Dr. Sajjad Ali (Pharm-D, M.Phil., R.Ph.
Drug Therapy of Gout
2. Drug therapy of gout - overview
• what is gout?
• what happens to patients with gout & why?
• what drugs are available for managing
gout?
• how are those drugs used?
3. Gout
• It is a disease in which defective
metabolism of uric acid causes arthritis,
especially in the smaller bones of the feet,
deposition of chalk-stones, and episodes
of acute pain.
4.
5.
6. Gout Pathophysiology
• Excessive production of uric acid in the
body
• Deposition of monosodium urate crystals
in joints & other tissues
• Crystal-induced inflammation
14. Drugs used to treat gout
Acute Arthritis Drugs
allopurinol
probenecid
febuxostat?
steroids
NSAID’s
colchicine
Urate Lowering Drugs
rest + analgesia + time
15. Colchicine - plant alkaloid
Cholchicine
obtained from
colchicum
autumnale
16. Colchicine
• “Only effective in gouty arthritis”
• does not affect renal excretion of uric acid
• does not alter plasma solubility of uric acid
• neither raises nor lowers serum uric acid
17. Mechanism of action of
cochicine
• Colchicine binds to tubulin, a micro-
tubular protein causing its de-
polymerization
• It blocks cell division by binding to the
mitotic spindles
• This disrupts cellular functions such as the
mobility of granulocytes, thus decreasing
their migration into the affected area
18.
19. Therapeutic uses
• It has anti-inflammatory activity and it is
used to relief pain associated with acute
gout within 12 hours
• NSAIDs have largely replaced colchicine
in the treatment of acute gouty attacks for
safety reasons
• Colchicine is used prophylactically
21. Adverse effects of colchicine
• Nausea
• GI disturbances
• Diarrhea
• Aplastic anemia
• Agranulocytosis
• Alopecia
22. NSAIDS
• NSAIDS are used effectively in
management of acute gouty arthritis
• Indomethacin is considered the classic
NSAID of the choice, although all NSAIDS
are found effective in treating pain and
inflammation associated with acute
arthritis
23. Allopurinol
• Allopurinol is a xanthine oxidase inhibitor
• It is a purine analogue
• It reduces the production of uric acid by
competitively inhibiting the two last steps
in the uric acid biosynthesis that are
catalyzed by xanthine oxidase
26. Therapeutic uses of allopurinol
• It is effective urate lowering therapy in the
treatment of gout and hyperuricemia
• It is recommended in chronic treatment of
gout
27. Pharmacokinetics
• Administered orally
• Completely absorbed from GIT
• The primary metabolite is alloxanthine which is also
inhibitor of xanthine oxidase
• It is administered as once daily dose
• Metabolites are excreted via feces and urine
• Dose should be reduced it creatinine clearance is less
than 50 ml/min
28. Adverse effects
• It is well tolerated
• Hypersensitivity adverse reactions may
occurs
• The most common hypersensitivity
reaction is skin rash
• In severe condition Stevens-Johnson
syndromes may occurs
30. Febuxostat
• It is recently approved by FDA
• It is oral xanthine oxidase inhibitor
• It is chemically distinct from allopurinol
• It has minimal adverse events
• It can be used in patients with renal
disease
31. Uricosuric therapy
Probenecid
• It blocks tubular reabsorption of uric acid
• It enhances urine uric acid excretion
• It increases urine uric acid level
• It decreases serum uric acid level
32. Uricosuric therapy
• moderately effective
• increases risk of nephrolithiasis
• not used in patients with renal disease
• frequent, but mild, side effects
• some drugs reduce efficacy (e.g., aspirin)
