Mechanism of Action:

• Bind tubulin causing depolymerization
  • Disrupts mobility of granulocytes to affected area
• Inhibits synthesis and release of inflammatory leukotrienes
  • Decreases attraction of neutrophils to the affected area
  • Anti-inflammatory activity is specific for gout

Colchicine

Indications:

• Alleviates pain of acute gouty arthritis within 12 hours
• Slow onset makes colchicine not a treatment of choice
• Primary use in prevention of recurrent attacks

Colchicine

Pharmacokinetics:

• Rapid oral absorption or parenteral administration
• Enterohepatic recirculation followed by excretion in feces (90 – 80%) or urine (10 – 20%)
• Dosage adjustment required for both renal or hepatic impairment
• T_1/2= 9 – 10 hrs

Adverse Reactions

• Pregnancy Category D
• Possibly unsafe during breastfeeding
• Common adverse reactions
  • Abdominal pain           
  • Nausea
  • vomiting
  • Diarrhea                       
  • Alopecia

Colchicine

Serious adverse reactions

o      Severe diarrhea     Bone marrow toxicity

o      Muscle wasting     Neuropathy           

o      Hypersensitivity    Multiple organ failure

·Risk of bone marrow toxicity often limits therapy with this drug to seven days or less

Colchicine

Mechanism of action

·Reversible inhibitor of cyclooxygenase

·Inhibits prostaglandin synthesis mediating inflammation, fever and pain.

Indomethacin

Indications

·Acute gouty arthritis (drug of choice)

·Ankylosing spondylitis

·Osteoarthritis of the hip

Indomethacin

Pharmacokinetics

·Available in oral and parenteral preparations

·Excreted in urine (60%) and bile and feces (33%)

·T_1/2 = 4.5 hrs

Indomethacin

Adverse reactions

·Pregnancy category B but use is not recommended in third trimester

·Possibly unsafe for use during breastfeeding

·Common reactions

o      Dyspepsia           

o      Nausea, vomiting

o      Inhibition of platelet aggregation

o      Headache           

o      Dizziness

Indomethacin

Serious adverse reactions

·Gastric ulceration and bleeding

·Cardiovascular or cerebrovascular event

o Myocardial infarction        

o Stroke        

o Hypertension

·Nephrotoxicity

·Hepatotoxicity

·Hypersensitivity

Indomethacin

Mechanism of action

·Inhibits xanthine oxidase required for uric acid biosynthesis

o      Precursors xanthine and hypoxanthine are more water soluble than uric acid

Allopurinol

Indications

·Drug of choice in treatment of chronic                    

tophaceous gout

·Hyperuricemia of gout

·Hyperuricemia secondary to other conditions

Allopurinol

Pharmacokinetics

·Administered orally and parenterally

·Biotransformed to alloxanthine (oxypurinol)

o Active inhibitor of xanthine oxidase

·Excreted in feces and urine

·T_1/2 allopurinol = 1-2 hrs

·T_1/2 oxypurinol =15 hrs

o Once daily dosing is practical

Adverse effects

Serious adverse effects

·Hypersensitivity reactions

·Bone marrow dysfunction

·Hepatotoxicity

·Renal failure

Mechanism of Action

·Inhibits urate-anion exchanger in proximal tubule, inhibiting urate reabsorption

o      At low doses they block proximal tubular secretion of uric acid

  This effect may make acute gouty arthritis worse by increasing serum uric acid levels

Probenecid & Sulfinpyrazone

Pharmacokinetics

·Pregnancy category B (probenecid), C (sulfinpyrazone)

·Safety unknown during breastfeeding

·Orally active

·Biotransformed to active metabolites

·Renally eliminated

·T_1/2 probenecid = 3 – 8 hrs,

o      High dose may increase T_1/2 to 6 – 12 hrs

·T_1/2 sulfinpyrazone =4 – 6 hrs, metabolite up to 14 hrs

Probenecid & Sulfinpyrazone

Adverse reactions

·Common reactions

o      Nausea                       

o      Dyspepsia

o      Rashes                       

o      Anemia

o      Headache                       

o      Dizziness

o      Precipitation of acute gouty arthritis and stone formation

Serious reactions

·Bone marrow depression

·Hypersensitivity