1. Understand the physiology of uric acid leading to the pathophysiology of gout and hyperuricemia
HGPRT and PRPP converts guanine to guanylic acid, preventing guanine from converting to xanthine and then uric acid. HGPRT and PRPP also converts hypoxantine back to inosinic acid, so it does not continue down the path to uric acid. So DEFICIENCY OF HGPRT increases uric acid.
2. Identify the clinical manifestations of gout / hyperuricemia
initially usually monoarticular in great toe. Intense sudden surge of pain. "podagra." untreated, attack peaks in 24-48 hours and lasts 3-14 days.
3. Know the treatment goals to managing patients with gout
main goal is prevention of attack. Want uric acid less than 6.
4. Apply the pharmacologic agents to the different diseases of gout
NSAIDs 1st line. Treat 24 until 24 hours after resolution, then taper 2-3 days. May take a week for resolution.
Uric acid is the final product of ___ metabolism.
t or f: the human body has no use for uric acid
t or f: hyperuricemia is usually asymptomatic
what is gout?
hyperuricemia with solidification of uric acid crystals that cause arthritis
2 ways for uric acid to accumulate?
"1. excess production (dietary, nucleic acids, de novo synth)
2. decreased excretion: 2/3 kidney, 1/3 GI"
Why is dehydration a risk factor for decreased uric acid excretion?
uric acid follows Na, so when sodium is reabsorbed as in dehydration, so it uric acid.
Stages of gout?
1. hyperuricemia 2. acute gouty arthritis 3. intercritical segment (symptom free period) 4. Chronic gouty stage
acute gouty arthritis: How are urate crystals formed?
water is evacuated from joint faster than urate. Synovial fluids become supersaturated, and so crystals deposit in tissues.
Explain immune response involved in gouty arthritis.
urate crystals are phagocytized by neutrophils. The sharp crystals lyse the neutrophils, causing them to spill inflammatory molecules.
t or f: indomethacin preferred NSAID for gout.
true but all NSAIDs have similar efficacy.
NSAIDs have FDA approval for gout:
naproxen, sulindac, endomethacin
T or F: corticosteroids suppress inflammation and are comparable to NSAIDs in acute gout.
Corticosteroids used in gout:
prednisone, IMmethylprednisolone, injected triamcinolone
Cautions for corticosteroids:
DM, GI problems, bleeding disorders, HTN, fluid retention, psych disorders
t or f: colchicine is a DOC for gout
prevents phagocytosis by neutrophils, thus preventing release of inflammatory molecules and lactic acid
t or f: caution with colchicine with P-gp or CYP 3A4 inhibs
recommended for prophy during intercritical (no sx) stage?
xanthine oxidase inhibitors
xanthine oxidase inhibitors include:
uricosuric agents MOA?
prevent tubular reabsorption of uric acid (thus incr excretion)
major side effects of uricosuric agents?
GI irritation (give with food), rash, exacerbate acute gout, and KIDNEY STONES (may give NaHCO3 or Shohl's sln)
uricosuric agents include:
probenecid dose adjust at what CrCl?
recombinant uricase (catalyzes oxidation of uric acid)
how to give pegloticase?
must be given with antihistamine AND steroid (high risk of hypersens)
tx for nephrolithiasis secondary to hyperuricemia?
hydration (2-3 L urine daily), aovid purine rich foods i.e. protein, urine pH above 6-6.5 (KHCO3 or K-citrate), avoid Na
Mainstay of treatment for recurrent gout-related kidney stone?
Uric acid level of hyperuricemia? Goal for gout tx?
over 7, under 6
How does acetazolamide fit in?
a carbonic anhydrase inhibitor, it increases H+ reabsorption and HCO3- secretion, thus alkalinizing the urine