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Block 2: Gout


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Where does the word gout come from?
Latin gutta for drops of poison
Normal serum level of urate in adult males?
5 mg/100 ml
Normal urate serum level in adult females?
3-4 mg/100 ml
Level of urate excreted in urine/day
600 mg
Solubility of urinc acid in serum
7 mg/100 ml *anthing over this is considered hyperuricemia
What are tophi?
Precipitations of monosodium urate crystals (ear, joints, kidney)
Causes of hyperuricemia
Increased production
Decreased renal clearance
Primary gout
Disorder of overproduction
Can primary gout be genetic?
Rarely some individuals have a low enzyme level of HG-PRTase
What happens in total loss of HG-PRTase?
Lesch-Nyhan Syndrome
Treatment regimen of gout
Anti-inflammatory drugs
Drugs that decrease urate production
Uricosuric drugs that enhance excretion
Anti-inflammatory drug
MA of Colchicine
Binds to tubulin in mirotubules and affects phagocytosis of urate crystals, halting inflammation
Duration of Cholchicine
6-12 hours
Why would you take Cholchicine prophylactically?
Avoid gouty attacks, also prevent attacks of Familial Mediterranean Fever (AA amyloid)
Is Cholchicine toxic?
Toxicity is common and results in vomiting and diarrhea
Who is Cholchicine toxicity most expected in?
Elderly with reduced renal function, they may get muscle weakness and myopathy
Anti-inflammatory effective in acute gouty attacks
What has Phenylbutazone fallen out of favor?
Severe toxicity- agranulocytosis and aplastic anemia. ESPECIALLY IN OLDER PATIENTS
Xanthine oxidaese inhibitor
MA of Allopurinol
Analog of hypoxanthine, inhibits XO
What is Allopurinol converted into?
Alloxanthine- also an inhibitor of XO (less potent, but lasts longer)
What is the consequence of XO inhibition?
Decreased urate excretion and increased oxypurine (hypoxanthine and xanthine) excretion
Does the total excretion of purines go down when gout patients are treated with allopurinol?
YES, because increased IMP and GMP acts as feedback (-) on purine syn. so overall purine production decreases
Why use allopurinol prophylactically?
Prevent attacks in chronic gout
What does an allergic rxn to allopurinol look like?
Skin eruptions, fever, and leukopenia
Are there any important drug interactions with allopurinol?
YES, the anticancer drug 6-mercaptopurine (metabolized by XO) is more toxic in the prescence of allopurinol.
Besides attacks, what eles does allopurinol prevent?
Calcium oxalate stones in the kidney in patients with hyperuricosuria
How do uricosurics work?
Promote excretion of urate in the kidney by blocking reabsorption in proximal tubule
Probenecid- low doses
uricosuric, may cause urate retention
Probenecid- high doses
Inhibits both secretion and reabsorption of urate
Probenecid- toxicity
GI distress, skin rashes, hyper-sensitivity
How do we prevent stone formation in those taking Probenecid?
Alkalining the urine
Should Probenecid be given during an acute gouty attack?
Uricosuric and anti-platelet drug
Sulfinpyrazone- toxicity
Affects on GI, especially dangerous for patients with peptic ulcers
What stage of gout are uricosuric drugs used?
Chronic gout- can promote reabsoption of gouty tophi
what are uricosuric drugs antagonized by?
Do you give Sulfinpyrazone during an acute attack?
NO, like probenecid can exacerbate acute attacks.
At what age does a fetus acquire fingerprints?
3 months

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