Drugs Used to Treat Gout Flashcards
what is gout the result of
increased uric acid in blood
hyperuricemia
when does uric acid deposit in or around joints
exceeds it solubility at pH 7.4
which gender has more cases of gout
male
when is gout seen more often in women
post-menopausal
what happens to uric acid when pH is lowered
Uric acid deposition lowered
- uric acid is converted to unionized form, poorly soluble in water
what are 2 ways drugs can induce hyperuricemia
- killing large numbers of cells
- decreasing renal recreation of urate by proximal tubular cells
what is the cycle of gout?
- crystals deposit in joint
- granulocytes phagocyte crystals
- granulocytes release kinins and lysosomal into blood stream
- increase lactic acid
- decrease pH
- increase urate deposition
who primarily excretes urate
kidneys
where is urate filtered
glomerulus
where is urate actively reabsorbed
early proximal tubule
late proximal tubule
distal tubule
what happens in the mid-section of the proximal tubule? what can inhibit this process
active secretion
- inhibition of secretion by weak acids occurs here
- urate retention
what are 3 non-drug therapy of gout
avoid obesity
avoid dehydration
avoid alcohol
what is the mechanism of Colchicine (6)
- decrease leukocyte mobilization
- decrease lactic acid production
- decrease leukocyte enzymes for leukocytes
- decrease release of histamine from mast cells
- decrease release of inflammatory glycoprotein from neutrophils following phagocytosis of urate crystals
- inhibit leukotriene synthesis
what are three general properties of Colchicine
antimitotic
anti-inflammatory
how does Colchicine decrease leukocyte mobilzition
binds and interferes with microtubule function to inhibit mobilization of leukocytes
how does Colchicine inhibit leukotriene synthesis
inhibits lipoxygenase pathway
what is the toxicity of Colchicine? with chronic use
GI ( nausea, vomiting, diarrhea)
chronic use - increase risk of aplastic anemia
therapeutic uses of Colchicine
treat acute gout
prevent acute attacks of gout
Name two Xanthine Oxidase inhibitors
Allopurinol (Zyloprim)
Febuxostat ( Uloric)
MOA of Allopurinol (Zyloprim)
- antimetabolite of hypoxanthine
what is the role of Hypoxanthine
inhibits enzyme xanthine oxidase to uric acid formation
how does Allupurinol work at low concentrations? high?
low: competitive inhibitor
high: non-competitive inhibitor
an active metabolite of Allpurinol ( alloxanthine) works how
at all concentrations is non-competitive inhibitor
what type of patients should get Allopurinol? why
- impaired renal function or history of renal urate stones
- does not increase renal urate levels
- xanthine oxidase inhibition products are water soluble
Allopurinol is combined with what other drugs
antineoplastic agents to prevent hyperuricemia
what is the toxicity of Allopurinol
uncommon,
rash, fever, vasculitis, hepatotoxicity
therapeurtic uses of Allopurinol
chronic gout
secondary hyperuricemia
what happens when someone starts using Allopurinol? how can this be fixed
acute attack of gout may precipitate due to fluctuations in serum urate levels and resulting dissolving of deposited
urate crystals
- Cholchicine or non-steroidal inflammatory: prevent symptoms of acute gout attack
MOA of Febuxostat
inhibition of Xanthine oxidase
Pharmacokinetics of Febuxostat
absorption reduced by Mg OH and Al OH antacids
-food slightly reduces absorption
what is Febuxostat used for
hyperuric patients w/ gout attacks
- not for asymptomatic hyperuricemia
what is the toxicity of Febuxostat
liver function abnormalities
nausea
joint pain
rash
what happens when a patient starts Febuxostat
cause acute attack of gout due to decreased serum levels of urate which mobilize urate from deposited crystals
what other drugs can you take Febuxostat with
NSAIDs or Cholchicine therapy
what is the MOA for Rasburicase ( Elitek) ? compared to other drugs
recombinant urate oxidase enzyme
- catalyzes oxidation of uric acid into soluble allantoin
- lowers uric plasma levels better than Allopurinol
define: allantoin
a crystalline compound formed in the nitrogen metabolism of many mammals
Who usually gets perscribed Rasburicase
pediatric patients with leukemia, lymphoma, and solid tumors who are receiving cancer chemotherapies treatments that will result in cell lysis and hyperuricemia
what is the toxicity of Rasburicase
hemolysis of GGPD deficient patients
- methemoglobinemia
- acute renal failure
Uricosuric agents name 2
Probenecid
Sulfinpyraozone
what is the MOA for Uricosuric agents
competitively inhibit active reabsorption of urate by URAT-1 in proximal tubule of nerphon to increase urate excretion
low doses of Uricosuric agents do what
only inhibit active secretion of urate to cause UA retention
what is the toxicity of Uricouric agents
GI irritation with aggrevation of peptic ulcer
sulfinpyrazone > Porbenecid
For Uricouric agents, what should the patient do to prevent intrarenal urate stone formation
increase fluid intake
what are theraputic uses of Uricouric agents
chronic gout
hyperuricemic states
- decreaes platelet aggregation : prophylactic treatment of mycardial infarction
where is Sulfinpyrazone not available
U.S.
Benzbromarone is a Uricouric agents and what does it do? who uses it? where is it availbale
- increases urate excretion without urate retention
- decreased renal function or allergic to probenecid or sulfinpyrazone
- used in Europe
what NSAIDS are FDA approved for gout
indomethacin
nproxen
sulindac
which NSAID should not be used for gout and why
aspirin
normal doses: decreases urate secretion
high doses: increase risk of renal calculi
what drugs are perfered for elderly patients with cardiac, renal or GI dseaes
NSAIDS or glucocorticoids over Colchicine
what os Glucocorticoids used for
acute gout with other threapies fail
