Gout

Colchicine

Colchicine

________ decreases movement of granulocytes into affected area.

Gout (hyperuricemia)

disorder characterized by high level of uric acid

Von-Gierke disease

a genetic disease, deficiency of glucose-6-phosphatase

main cause of gout

under excretion of uric acid

secondary cause

cause outside the pathway of purine synthesis

examples of secondary causes of gout

1. Increase nuclei acids in diet

2. Increased cellular breakdown

3. Von-Gierke disease

primary cause

defect of one or more of enzymes of purine synthesis

examples of primary causes of gout

1. Genetic mutation of PRPP synthetase

2. Lesch-Nyhan syndrome

Lesch-Nyhan syndrome

• genetic defect in HGPRT (Hypoxanthine-guanine phosphoribosyltransferase)

suicide inhibition:

a type of inhibition in which a substrate analog is converted to an inhibitor not released from the enzyme active site

Insoluble sodium urate crystals precipitate into:

• joints

• kidneys

• soft tissues

gouty arthritis

deposition of needle shaped urate crystals in joints causing severe inflammation

most commonly affected joint

big toe joint

Goals of treatment for gout:

• Rapid pain relief in acute attacks

• Prevention of future gout attacks and the complications, by decreasing formation of uric acid

Allopurinol

• analog of hypoxanthine

• competitive inhibitor to xanthine oxidase

• a suicide enzyme inactivator

Probenecid

• Drugs that increase uric acid excretion

  • effective in regulation of hyperuricemia and prevention of tophii

Acute Attack treatment

• analgesics and anti-inflammatory

• colchicine decreases movement of granulocytes into affected area

• colchicine and non-steroidal anti-inflammatory drugs can be used prophylactically to prevent acute attacks in patients with gouts

Alkalinization of urine

increase solubility of uric acid in urine

uric acid stones

Deposition of sodium urate crystals in the kidney

ethanol

decreases excretion of uric acid