Block 2: Gout
Terms
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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 - Colchicine
- 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
- Phenylbutazone
- Anti-inflammatory effective in acute gouty attacks
- What has Phenylbutazone fallen out of favor?
- Severe toxicity- agranulocytosis and aplastic anemia. ESPECIALLY IN OLDER PATIENTS
- Allopurinol
- 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?
-
Hydration
Alkalining the urine - Should Probenecid be given during an acute gouty attack?
- NO
- Sulfinpyrazone
- 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?
- Salicylates
- 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