Gout Therapeutics

Question 1

What is the MOA of NSAIDs?

Answer 1

inhibit production of PGEs, reducing pain and inflammation

Question 2

What is the MOA of Indomethacin?

Answer 2

inhibit urate crystal phagocytosis, anti-inflammatory effect

Question 3

What is the MOA of anti-mitotics?

Answer 3

inhibit b-tubulin polymerization = disrupt cytoskeletal function
prevent activation, degranulation, migration of neutrophils

Question 4

What is the MOA of corticosteroids?

Answer 4

suppress inflammation, cross cell membrane and bind to glucocorticoid receptors
alter mRNA synthesis: upregulate anti-inflamm genes and downregulate inflamm genes

Question 5

What is the MOA of Xanthine Oxidase Inhibitors?

Answer 5

reduces uric acid biosynthesis
decreases serum uric acid levels
prevents conversion of xanthine and hypoxanthine into uric acid

Question 6

What is the MOA of uricosurics?

Answer 6

increases excretion of UA in urine
inhibits active reabsorption of UA in proximal tubule of kidney by inhibiting URT and OAT

Question 7

What is the MOA of uricases?

Answer 7

recombinant pegylated uricase, converts uric acid to soluble allantoin that is easily excreted by the kidney

Question 8

What are the NSAIDs used for gout?

Answer 8

Celecoxib (COX2)
Naproxen
Indomethacin

Question 9

What are the anti-mitotic agents used for gout?

Answer 9

Colchicine

Question 10

What are the corticosteroids used for gout?

Answer 10

Prednisone (PO)
Methylprednisolone (IA)

Question 11

What are the xanthine oxidase inhibitors used for gout?

Answer 11

Allopurinol
Febuxostat

Question 12

What are the uricosurics used for gout?

Answer 12

Probenecid
Losartan (active metabolite treats HTN)
Fenofibrate (also hyperlipidemia)

Question 13

What are the uricases used for gout?

Answer 13

Pegloticase
Rasburicase

Question 14

Indomethacin dose for acute flare

Answer 14

75mg stat, 50mg PO TID x 4-5 days

Question 15

Naproxen dose for acute flare

Answer 15

750mg stat, 500mg PO BID x 4-5 days

Question 16

Naproxen dose for prophylaxis

Answer 16

250mg PO BID

Question 17

Celecoxib dose for acute flare

Answer 17

200mg PO BID x 4-5 days

Question 18

Colchicine dose for acute flare

Answer 18

1.2mg stat, then 0.6mg 1 hour later, followed by 0.6mg OD-BID 12 hours later until resolved

Question 19

Colchicine dose for prophylaxis

Answer 19

0.6mg PO OD-BID

Question 20

Prednisone dose for acute flare

Answer 20

20-50mg PO DY x 5-10 days (0.5mg/kg/day)

Question 21

Prednisone dose for prophylaxis

Answer 21

< or = 10mg PO DY

Question 22

Allopurinol dose for prophylaxis

Answer 22

100mg PO DY, titrate Q2-5W (usual dose 300mg DY), max 800mg

Question 23

Febuxostat dose for prophylaxis

Answer 23

40mg PO DY, can titrate up to 80mg PO DY

Question 24

Probenecid dose for prophylaxis

Answer 24

500mg PO DY, can titrate Q4W to max dose 3g

Question 25

Colchicine important interactions

Answer 25

+ clarithromycin = DEATH
+ CYP3A4 inhibitor = increased serum levels
+ P-gp inhibitor = increased serum levels

Question 26

Prednisone important interactions

Answer 26

+ NSAIDs = GI toxicity

Question 27

Allopurinol important interactions

Answer 27

+ azathioprine= increased effects
+ 6-mercaptopurine = increased effects
+ warfarin = inhibits metabolism
+ febuxostat = increase effects of azathioprine and 6-MP
+ probenecid = inhibits metabolism but used together causes increased efficacy?

Question 28

Febuxostat important interactions

Answer 28

+ allopurinol = increased effects of azathioprine and 6-MP

Question 29

Probenecid important interactions

Answer 29

+ allopurinol= inhibits conversion to oxypurinol but together causes increased efficacy?

Question 30

Thiazides and Loop diuretics interactions

Answer 30

induce/worsen gout
dehydration may impact renal clearance?