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Gout Pharm + Path

Pathophysiology of Gout and Pharmacology

QuestionAnswer
What is gout? Increased uric acid in the joints
What are the two causes of gout? 1. Over production of pruine nucleotides, giving excessive uric acid 2. Impaired uric acid excretion through kidneys (drugs/toxins can have an affect here)
What is colchcine indicated for? Acute gouty arthritis. It is an antimitotic tubulin inhibitor used for an anti-inflammatory action only.
What is the MOA for colchicine? Causes the loss of fibrillar tubules in granuolocytes, inhibiting neutrophil migration, chemotaxis, adhesion+ phagocytosis in inflamed areas. Decreases histamine release from mast cells, prodn of glycoproteins, collagen formation.
How long before colchicine provides pain relief? 12 hours or less
What are the precautions for using colchcine? GI diseases (damages GI cells), renal impairment, hepatic impairment, pregnancy, elderly (dehydration and electrolyte loss)
What ADR's can colchicine toxicity cause? NVD, abdominal pain, rash, myopathy, leukopenia, can decrease body temperature, can cause respiratory depression.
Giving colchicine via IV can cause less GI disturbance, but what is the risk of administering this way? Narrow TI, increases risk of sepsis.
How long is the half life of colchicine? 9 hours
How is colchicine excreted? Biliary clearance with some enterohepatic clearance
Which drugs can increase colchicine conc in the blood? CYP3a4 inhibitors
What is the danger of increasing colchicine conc in the blood? Can cause toxic effects if person is kidney or liver impaired.
What class of drug is allopurinol? Xanthine oxidase inhibitor
What is allopurinol's MOA? Decreases uric acid concentration in urine to below solubility
What are the contra-indications for allopurinol? Breast feeding, children, anyone with hyersensitivity to allopurinol
How is allopurinol excreted? Renally
What are some of the other indications for allopurinol? Leukemia and lymphoma
Name the uricosuric agents Probenecid and benzbromarone
What is the MOA of uricosuric agents? Increases the rate of uric acid excretion by kidneys, inhibiting tubular reabsorption of uric acid.
How long does probenecid last for? 12 hours, so twice daily dosing
True or false: probenecid has anti-inflammatory and analgesic properties Fasle, has neither
What other compounds does probenecid keep in circulation? Penicillins, methotrexate, clofibrate, many NSAIDS
Probenecid isn't useful in someone with Low kidney function
What is the key to probenecid dosing? Has a paradoxical action, needs high dosing to increase excretion of uric acid.
Why does benzbromarone have low use in Aus? Hepatotoxicity issues
What type of drug is rasburicase? Urate oxidase enzyme
How long does benzbromarone last for? 24 hours
How long does probenecid last for? Plasma half life 5-8 hours (dose dependent), 24 hour half life for metabolite
How long is the half life of allopurinol? 25 hour haf life for active metabolite, 2-3 hour plasma half life
What is the MOA of urate oxidase enzymes? Converts uric acid to soluble allantoin, less ppt in joints, renal tubules.
What is the dose for rasburicase? 0.2mg/kg for 5-7 days, given as IV infusion over 30 minutes.
What are the ADR's for rasburicase? Acute renal failure, anaphylaxis, haemolytic anaemia, contra indicated in those with g6pd deficiency
What isn't given in an acute gout attack? allopurinol and uricosuric acids, can increase severity as they mobilise urare from the joints. Ethanol, cyclosprin A, thiazide diuretics also not given.
What is given in an acute gout attack? NSAIDS (if not C/I) but no salicylates. Salicylate can elevate uric acid levels and antagonise action of probenecid and sulfinpyrazole
Created by: LDM
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