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D & T exam 2 > Drugs Used to Treat Gout > Flashcards

Drugs Used to Treat Gout Flashcards

1
Q

what is gout the result of

A

increased uric acid in blood

hyperuricemia

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2
Q

when does uric acid deposit in or around joints

A

exceeds it solubility at pH 7.4

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3
Q

which gender has more cases of gout

A

male

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4
Q

when is gout seen more often in women

A

post-menopausal

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5
Q

what happens to uric acid when pH is lowered

A

Uric acid deposition lowered

- uric acid is converted to unionized form, poorly soluble in water

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6
Q

what are 2 ways drugs can induce hyperuricemia

A
  • killing large numbers of cells

- decreasing renal recreation of urate by proximal tubular cells

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7
Q

what is the cycle of gout?

A
  • crystals deposit in joint
  • granulocytes phagocyte crystals
  • granulocytes release kinins and lysosomal into blood stream
  • increase lactic acid
  • decrease pH
  • increase urate deposition
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8
Q

who primarily excretes urate

A

kidneys

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9
Q

where is urate filtered

A

glomerulus

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10
Q

where is urate actively reabsorbed

A

early proximal tubule
late proximal tubule
distal tubule

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11
Q

what happens in the mid-section of the proximal tubule? what can inhibit this process

A

active secretion

  • inhibition of secretion by weak acids occurs here
  • urate retention
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12
Q

what are 3 non-drug therapy of gout

A

avoid obesity
avoid dehydration
avoid alcohol

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13
Q

what is the mechanism of Colchicine (6)

A
  • 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
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14
Q

what are three general properties of Colchicine

A

antimitotic

anti-inflammatory

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15
Q

how does Colchicine decrease leukocyte mobilzition

A

binds and interferes with microtubule function to inhibit mobilization of leukocytes

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16
Q

how does Colchicine inhibit leukotriene synthesis

A

inhibits lipoxygenase pathway

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17
Q

what is the toxicity of Colchicine? with chronic use

A

GI ( nausea, vomiting, diarrhea)

chronic use - increase risk of aplastic anemia

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18
Q

therapeutic uses of Colchicine

A

treat acute gout

prevent acute attacks of gout

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19
Q

Name two Xanthine Oxidase inhibitors

A

Allopurinol (Zyloprim)

Febuxostat ( Uloric)

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20
Q

MOA of Allopurinol (Zyloprim)

A
  • antimetabolite of hypoxanthine
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21
Q

what is the role of Hypoxanthine

A

inhibits enzyme xanthine oxidase to uric acid formation

22
Q

how does Allupurinol work at low concentrations? high?

A

low: competitive inhibitor
high: non-competitive inhibitor

23
Q

an active metabolite of Allpurinol ( alloxanthine) works how

A

at all concentrations is non-competitive inhibitor

24
Q

what type of patients should get Allopurinol? why

A
  • impaired renal function or history of renal urate stones
  • does not increase renal urate levels
  • xanthine oxidase inhibition products are water soluble
25
Q

Allopurinol is combined with what other drugs

A

antineoplastic agents to prevent hyperuricemia

26
Q

what is the toxicity of Allopurinol

A

uncommon,

rash, fever, vasculitis, hepatotoxicity

27
Q

therapeurtic uses of Allopurinol

A

chronic gout

secondary hyperuricemia

28
Q

what happens when someone starts using Allopurinol? how can this be fixed

A

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

29
Q

MOA of Febuxostat

A

inhibition of Xanthine oxidase

30
Q

Pharmacokinetics of Febuxostat

A

absorption reduced by Mg OH and Al OH antacids

-food slightly reduces absorption

31
Q

what is Febuxostat used for

A

hyperuric patients w/ gout attacks

- not for asymptomatic hyperuricemia

32
Q

what is the toxicity of Febuxostat

A

liver function abnormalities
nausea
joint pain
rash

33
Q

what happens when a patient starts Febuxostat

A

cause acute attack of gout due to decreased serum levels of urate which mobilize urate from deposited crystals

34
Q

what other drugs can you take Febuxostat with

A

NSAIDs or Cholchicine therapy

35
Q

what is the MOA for Rasburicase ( Elitek) ? compared to other drugs

A

recombinant urate oxidase enzyme

  • catalyzes oxidation of uric acid into soluble allantoin
  • lowers uric plasma levels better than Allopurinol
36
Q

define: allantoin

A

a crystalline compound formed in the nitrogen metabolism of many mammals

37
Q

Who usually gets perscribed Rasburicase

A

pediatric patients with leukemia, lymphoma, and solid tumors who are receiving cancer chemotherapies treatments that will result in cell lysis and hyperuricemia

38
Q

what is the toxicity of Rasburicase

A

hemolysis of GGPD deficient patients

  • methemoglobinemia
  • acute renal failure
39
Q

Uricosuric agents name 2

A

Probenecid

Sulfinpyraozone

40
Q

what is the MOA for Uricosuric agents

A

competitively inhibit active reabsorption of urate by URAT-1 in proximal tubule of nerphon to increase urate excretion

41
Q

low doses of Uricosuric agents do what

A

only inhibit active secretion of urate to cause UA retention

42
Q

what is the toxicity of Uricouric agents

A

GI irritation with aggrevation of peptic ulcer

sulfinpyrazone > Porbenecid

43
Q

For Uricouric agents, what should the patient do to prevent intrarenal urate stone formation

A

increase fluid intake

44
Q

what are theraputic uses of Uricouric agents

A

chronic gout
hyperuricemic states
- decreaes platelet aggregation : prophylactic treatment of mycardial infarction

45
Q

where is Sulfinpyrazone not available

A

U.S.

46
Q

Benzbromarone is a Uricouric agents and what does it do? who uses it? where is it availbale

A
  • increases urate excretion without urate retention
  • decreased renal function or allergic to probenecid or sulfinpyrazone
  • used in Europe
47
Q

what NSAIDS are FDA approved for gout

A

indomethacin
nproxen
sulindac

48
Q

which NSAID should not be used for gout and why

A

aspirin
normal doses: decreases urate secretion
high doses: increase risk of renal calculi

49
Q

what drugs are perfered for elderly patients with cardiac, renal or GI dseaes

A

NSAIDS or glucocorticoids over Colchicine

50
Q

what os Glucocorticoids used for

A

acute gout with other threapies fail

D & T exam 2 (27 decks)

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