Drugs used in
the Management of Gout
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Pharmacological Treatment
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Mechanistic Basis: management of gout
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Sequence of
Pathophysiological Events:
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phagocytosis by
synoviocytes of urate crystals
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Synoviocytes release:
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prostaglandins
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interleukin 1
(IL-1)
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lysosomal enzymes
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These chemotactic mediators
attract:
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Increased numbers of
mononuclear phagocytes (macrophages):
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This sequence suggests most
effective drugs would be those that suppress
different phases of the inflammatory process
(leukocyte activation)
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Colchicine
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Overview:colchicine
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Pharmacokinetics:colchicine
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readily absorbed following
oral route administration
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peak plasma levels: two
hours
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Drug metabolites:
intestinal tract & urinary excretion
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Pharmacodynamics: colchicine
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Mechanism of
Action:colchicine
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binds to
intracellular protein -- tubulin
®
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consequent inhibition
of tubulin polymerization to form microtubules®
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inhibition of
leukocyte migration/phagocytosis;inhibition of leukotriene
B4
formation.
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Indications for
Clinical Use:colchicine
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Effective in alleviating
inflammation/pain associate with acute
gouty arthritis
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Colchicine: increased gout
specificity compared to NSAIDs
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Diarrhea, associated with
colchicine: has led to NSAIDs being very frequently used
instead
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Colchicine preferred:
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Adverse Effects:colchicine
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Diarrhea (common)
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nausea, vomiting, the bowel
pain
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Rarely: hair loss;bone
marrow depression, peripheral neuritis, myopathy
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Acute, very large
colchicine doses (non-therapeutic):
Nonsteroidal
Anti-inflammatory Drugs in Gout
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Overview
NSAIDS
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Rationale:NSAIDS:
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inhibition of urate crywstal phagocytosis
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inhibition of prostaglandin synthase
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Indomethacis is an initial treatment (agent most often used
currently); it is an alternative to colchicine. Other
NSAIDs have been used in managing acute gouty arthritis with
the exception of aspirin, salicylates and tolmetin.
Oxaprozin should not be used in patients with uric acid
stones because oxaprozin lowers serum uric acid, thereby
increasing uric acid excretion in the urine.
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Uricosuric Drugs
Allopurinol
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