Hyperuricemia and Gout Flashcards
What is Hyperuricemia?
It is defined as having a plasma concentration of Uric Acid > 7mg/dl
How soluble is Uric Acid? What is the consequence of it’s solubility?
Not very soluble, so [UA] > 9 mg/dl = crystals in acid environment
What are the two causes of Hyperuricemia?
Metabolic (10%) and Renal (90%)
Describe the metabolic cause of hyperuricemia.
These are over producers. Primary from increased PRPP synthetase of decreased HGPRT (in mediterraneans) or Secondary from myelo/lympho proliferative disorders (this is more purine turnover) or chemo/radiation (cells dying release purine)
Describe the renal cause of hyperuricemia.
These are the under secretors. Primary from CKD/renal failure. Secondary from long term diuretic therapy (increased resorption of uric acid) and toxemia of pregnancy
What is gout?
The deposition of uric acid crystals in joint spaces
What is it called if gout is in the great toe?
Podagra
What is acute gouty arthritis?
When uric acid crystals in joint spaces break leading to severe acute pain
What is tophaeceous grout?
A chronic form of gout, tophi are nodules of uric acid
How is uric acid handles in the kidneys?
It is filtered then reabsorbed in the proximal C.T. then secreted and partially reabsorbed again
What is the first attempt at treatment for gout?
Stop eating meat - non pharmaceutical
What are the 5 aims of treatment for gout? (remember these, they will be used when describing the uses of drugs)
1) Terminate an acute attack
2) Prevent recurrence of acute gouty arthritis
3) Revers or prevent complications of deposited ureate crystals
4) Prevent other factors associated with disease (obesity, HTN, hypertrigliceridemia
5) Prevent formation of Uric acid nephroliths
What is Colchicine used for?
1 and 2; effective only against gouty arthritis and prophylaxis against attacks
What is the MOA of Colchicine?
Prevent depolymerization of microtubules in PMNs so they can’t move, inhibits polys from making inflammatory cytokines; This terminates attacks of gout and prevents recurrence of gouty arthritis; useful in Mediterranean fever
How is Colchicine met/elim?
Hepatically metabolized mainly by deacetylation and excreted through biliary system (up to 20% in urine)
What are the acute ADE’s with Colchicine?
GI effects (N/V, diarrhea, anorexia, lactose intolerance); these are dose related
What are the chronic ADEs with Colchicine?
Blood dyscrasias; Bone marrow suppression (associated with later stage of colchicine fox after GI adverse effects)
Why is impaired renal and hepatic function important in Colchicine?
Because it leads to elevated serum drug levels which leads to increase in toxicity; in particular, myopathy, peripheral neuropathy, and rhabdo have all been reported in patients taking colchicine, especially in overdose