ANTI-GOUT
DRUGS
GOUT
A
familial
metabolic
disease
characterized by recurrent episodes
of acute arthritis due to deposits of
monosodium urate in joints &
cartilage.
GOUT
Treatment aims to:
 Relieve
acute gouty attacks
- Colchicine, NSAIDs, corticosteroids
 Prevent
-
-
recurrent gouty episodes
Uricosuric agents
Allopurinol
CLASSIFICATION of
antigout drugs
1.
2.
3.
4.
Colchicum alkaloids
Colchicine
Nonsteroidal anti-inflammatory
drugs
Naproxen, indomethacin,
phenylbutazone, ibuprofen
Uricosuric agents
Probenecid, sulfinpyrazone
Urate synthesis inhibitors
Allopurinol
COLCHICINE
An alkaloid (colchicum autumnale)
Relieves pain & inflammation of gouty
arthritis in 12-24 hrs
MOA


inhibits the polymerization of tubulin (a
structural protein necessary for motility)
- inhibits leukocyte migration
reduces the phagocytosis of urate
crystals by leukocytes
Adverse Effects
Diarrhea - bloody
 Nausea, vomiting & abdominal pain
 Hair loss
 Bone marrow depression
 Peripheral neuritis
 Myopathy
 Acute intoxication: burning throat pain,
bloody diarrhea, shock, hematuria
 Fatal ascending CNS depression

NSAIDs:
Anti inflammatory ( inhibiting urate
crystal phagocytosis) & analgesic
effects
 Indomethacin is most commonly
used NSAID- uricosuric
 All NSAIDs except aspirin,
salicylates & tolmetin

URICOSURIC AGENTS
PROBENECID
SULFINPYRAZONE
Organic acids
MOA


inhibit the reabsorption of uric acid in
the proximal part (S2) of the nephron
may also reduce secretion of uric acid
into the nephron (proximal tubule), but
reduction of reabsorption is the
dominant (& therapeutic) effect
Adverse effects

Gastrointestinal irritation

Rash

Nephrotic syndrome with probenecid

Aplastic anemia
ALLOPURINOL
Standard of care therapy in the intercritical
period
Reduces total uric acid body burden
MOA


Allopurinol is converted to alloxanthine by
xanthine oxidase
Inhibits the production of less soluble uric
acid by xanthine oxidase from more
soluble xanthine & hypoxanthine
Pharmacokinetics

80-90% absorbed after oral
administration

short half-life(1-2hours),but
metabolite alloxanthine (oxipurinol)
has a half-life of about 15 hours
Adverse effects









Acute attacks of gouty arthritis (prophylactic
treatment with NSAIDs or colchicine)
GI intolerance
Peripheral neuritis
Necrotizing vasculitis
Bone marrow depression
Aplastic anemia
Hepatic toxicity, Interstitial nephritis
Allergic skin reactions-exfoliative dermatitis
Cataract formation
Interactions



Inhibits the metabolism of 6mercaptopurine and azathioprine so their
dosage must be reduced by 75%
Prolongs t1/2 of warfarin & probenecid
(inhibits metabolism)
May enhance the bone marrow toxicity of
cytotoxic drugs (cyclophosphamide)
Caution: Safety in children & during
pregnancy has not been established
FEBUXOSTAT
Recently approved first non-purine
inhibitor of xanthine oxidase
 Safe in renal disease as highly
metabolized to inactive metabolites in
the liver

GLUCOCORTICOIDS
 INTERLEUKIN-1 INHIBITORSanakinra – under investigation

Thank u!