Drugs Used to Treat Gout

Question 1

what is gout the result of

Answer 1

increased uric acid in blood

hyperuricemia

Question 2

when does uric acid deposit in or around joints

Answer 2

exceeds it solubility at pH 7.4

Question 3

which gender has more cases of gout

Answer 3

male

Question 4

when is gout seen more often in women

Answer 4

post-menopausal

Question 5

what happens to uric acid when pH is lowered

Answer 5

Uric acid deposition lowered

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

Question 6

what are 2 ways drugs can induce hyperuricemia

Answer 6

• killing large numbers of cells

- decreasing renal recreation of urate by proximal tubular cells

Question 7

what is the cycle of gout?

Answer 7

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

Question 8

who primarily excretes urate

Answer 8

kidneys

Question 9

where is urate filtered

Answer 9

glomerulus

Question 10

where is urate actively reabsorbed

Answer 10

early proximal tubule
late proximal tubule
distal tubule

Question 11

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

Answer 11

active secretion

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

Question 12

what are 3 non-drug therapy of gout

Answer 12

avoid obesity
avoid dehydration
avoid alcohol

Question 13

what is the mechanism of Colchicine (6)

Answer 13

• 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

Question 14

what are three general properties of Colchicine

Answer 14

antimitotic

anti-inflammatory

Question 15

how does Colchicine decrease leukocyte mobilzition

Answer 15

binds and interferes with microtubule function to inhibit mobilization of leukocytes

Question 16

how does Colchicine inhibit leukotriene synthesis

Answer 16

inhibits lipoxygenase pathway

Question 17

what is the toxicity of Colchicine? with chronic use

Answer 17

GI ( nausea, vomiting, diarrhea)

chronic use - increase risk of aplastic anemia

Question 18

therapeutic uses of Colchicine

Answer 18

treat acute gout

prevent acute attacks of gout

Question 19

Name two Xanthine Oxidase inhibitors

Answer 19

Allopurinol (Zyloprim)

Febuxostat ( Uloric)

Question 20

MOA of Allopurinol (Zyloprim)

Answer 20

• antimetabolite of hypoxanthine

Question 21

what is the role of Hypoxanthine

Answer 21

inhibits enzyme xanthine oxidase to uric acid formation

Question 22

how does Allupurinol work at low concentrations? high?

Answer 22

low: competitive inhibitor
high: non-competitive inhibitor

Question 23

an active metabolite of Allpurinol ( alloxanthine) works how

Answer 23

at all concentrations is non-competitive inhibitor

Question 24

what type of patients should get Allopurinol? why

Answer 24

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

Question 25

Allopurinol is combined with what other drugs

Answer 25

antineoplastic agents to prevent hyperuricemia

Question 26

what is the toxicity of Allopurinol

Answer 26

uncommon, | rash, fever, vasculitis, hepatotoxicity

Question 27

therapeurtic uses of Allopurinol

Answer 27

chronic gout | secondary hyperuricemia

Question 28

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

Answer 28

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

Question 29

MOA of Febuxostat

Answer 29

inhibition of Xanthine oxidase

Question 30

Pharmacokinetics of Febuxostat

Answer 30

absorption reduced by Mg OH and Al OH antacids | -food slightly reduces absorption

Question 31

what is Febuxostat used for

Answer 31

hyperuric patients w/ gout attacks | - not for asymptomatic hyperuricemia

Question 32

what is the toxicity of Febuxostat

Answer 32

liver function abnormalities nausea joint pain rash

Question 33

what happens when a patient starts Febuxostat

Answer 33

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

Question 34

what other drugs can you take Febuxostat with

Answer 34

NSAIDs or Cholchicine therapy

Question 35

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

Answer 35

recombinant urate oxidase enzyme - catalyzes oxidation of uric acid into soluble allantoin - lowers uric plasma levels better than Allopurinol

Question 36

define: allantoin

Answer 36

a crystalline compound formed in the nitrogen metabolism of many mammals

Question 37

Who usually gets perscribed Rasburicase

Answer 37

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

Question 38

what is the toxicity of Rasburicase

Answer 38

hemolysis of GGPD deficient patients - methemoglobinemia - acute renal failure

Question 39

Uricosuric agents name 2

Answer 39

Probenecid | Sulfinpyraozone

Question 40

what is the MOA for Uricosuric agents

Answer 40

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

Question 41

low doses of Uricosuric agents do what

Answer 41

only inhibit active secretion of urate to cause UA retention

Question 42

what is the toxicity of Uricouric agents

Answer 42

GI irritation with aggrevation of peptic ulcer | sulfinpyrazone > Porbenecid

Question 43

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

Answer 43

increase fluid intake

Question 44

what are theraputic uses of Uricouric agents

Answer 44

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

Question 45

where is Sulfinpyrazone not available

Answer 45

U.S.

Question 46

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

Answer 46

- increases urate excretion without urate retention - decreased renal function or allergic to probenecid or sulfinpyrazone - used in Europe

Question 47

what NSAIDS are FDA approved for gout

Answer 47

indomethacin nproxen sulindac

Question 48

which NSAID should not be used for gout and why

Answer 48

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

Question 49

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

Answer 49

NSAIDS or glucocorticoids over Colchicine

Question 50

what os Glucocorticoids used for

Answer 50

acute gout with other threapies fail