Gout Flashcards
Define the gout ..
It is metabolic disease in which plasma urate level is raised
Causes of gout:
Overproduction of uric acid (20%)
Reduced renal excretion of uric acid (80%)
E.g of overproduction of uric acid:
Excessive cell destruction (lymphoproliferative disorders) especially during their treatment
Or inherited defects that increase purine synthesis.
E.g of reduced renal excretion:
Renal failure
Drugs, e.g most diuretics, low dose aspirin
Lactate that formed from alcohol can reduce the tubular secretion of uric acid
Hyperuricemia can lead to deposition of sodium urate crystals in tissues, especially :
Joints and kidney
Characteristics of gout:
Chatacterized by recurrent episodes of acute arthritis and formation of uric acid calculi in the kidneys
Gout causes acute arthritis due to:
Deposits of monosodium urate in joints and cartilage
Drug used to treat gout may act in the following ways:
By inhibiting uric acid synthesis
Increasing uric acid excretion
Inhibiting leukocyte migration into the joint
By a general anti-inflammatory and analgesic effect (NSAIDs).
Drugs that inhibit uric acid synthesis :
Allopurinol
The main prophylactic drug for gout:
Allopurinol
Drugs that increase uric acid excretion
uricosuric agents: probenecid and sulfinpyrazone
Drug that inhibits leukocyte migration into the joint:
Colchicine
Causes of acute gout:
Excessive alcohol consumption, a diet rich in purines, or kidney disease
Drugs used in acute gout:
NSAIDs
Glucocorticoids
Colchicine
Causes of chronic gout:
Genetic defect that increase the rate of purine synthesis
Renal deficiency
Excessive production of uric acid associated with cancer chemotherapy
Drugs used in chronic gout :
Uricosuric drugs: probencid, sulfinpyrazone
Allopurinol
Cholchicine
Plant alkaloid used for treatment of acute and chronic gout:
Colchicine
Mechanism of action of colchicine:
It bind to tubulin causing its depolymerization, thus decreasing migration of granulocytes into the effected area
It blocks cell division by binding to mitotic spindles
It also inhibits the synthesis and release of the leukotrients
Pharmacokinetic of colchicine
It is administered orally
It is recycled in the bile and is excreted unchanged in the feces or urine
Colchicine using should be avoided in :
in patients with a creatinine clearance of less than 50 mL/min.
Adverse effects of colchicine:
nausea, vomiting, abdominal pain and diarrhea
Chronic administration may lead to myopathy, neutropenia, aplastic anemia and alopecia.