gout Flashcards
can make dx of gout on
symptoms
serum uric acid levels
colchicine only works for
gout
not other arthritis
Primary gout is a familial disorder that is thought to result from genetically-determined errors of
purine metabolism or uric acid excretion that lead to increased circulating levels of uric acid.
secondary gout from
drugs, diet, disease states
uric acid is the major end product of
purine metabolism (adenine, guanine)-->xanthine-->uric acid (no physio function) try to excrete
??? increase levels and catabolism of purines
-high purine diet, heavy alcohol consumption, surgery, certain drugs, etc–> can increase uric acid formation
90% uric is filtered at the ??
10%
-problem if..
glomerulus (~90%)
(~10%), by active secretion through the organic acid secretory system in the proximal tubule
-drugs may compete for transporter: low-dose ASA, diuretics
decreased function of kidney (hypo perfusion) caused by ??? may cause build up of uric acid
heart failure
about 75-90% of the uric acid/urate ion in the tubular fluid can be
reabsorbed in the proximal tubule by the anion exchange transport system
-if hard time reabsorbing uric acid–>potential gout
Normal values for plasma urate/uric acid
solubility of uric acid in water
pKa?
- 0-7.0 mg/deciliter or 120- 420 μM
- 68 g/L (approach solubility! about 5L blood in body)
pKa of 5.7
more soluble at high pH(alkaline)
factors contrib. to hyperuricemia/gout
Heredity Diet Alcohol (often a major factor) Low fluid intake Cancer Radiation therapy Drugs
hyperuricemia/gout inducing drugs
aspirin (low-moderate doses) diuretics (especially thiazides) sulfonamide antimicrobials antineoplastics (anticancer drugs) l-DOPA
25% of gout pts have attacks even though..
also, many ppl with mild hyperuricemia never…
their uric acid levels are in normal range
develop gout
steps in acute gout attack:
- sodium urate crystals form in joint
- phagocytosis by neutros and macros
- neutro activation and release of inflamm. mediators (PGs, LKs, NO, Superoxide) triggers inflammatory reaction
also the generation of lactic acid and other acidic metabs lower pH–>inc. urate crystal formation
4 stages of gout
Asymptomatic hyperuricemia (may progress to gout)
Acute gouty arthritis
Intercritical (interval) gout
Chronic tophaceous gout (+/- progressive renal failure)
Chronic tophaceous gout dev. from
deposition of urate crystals in the kidney and renal calculi
pharm approach: suppress acute attack
1st: NSAIDs
indomethacin* (traditional)
ibuprofen
ketorolac (emerging!)
(acetaminophin: no anti-inflammatory)
2nd: Colchicine (Colcrys)
3rd: Corticosteroids - prednisone, methylprednisolone
indomethacin has a…
indol ring
can produce CNS effects that other NSAIDS don’t
-behavioral diffs, hallucinations, diff concentrating
-cause ha
toxic to GIT, CV events
don’t use chronically