Pharm - Gout

Question 1

describe the pathway from purines to uric acid

Answer 1

GMP –> guanosine –> guanine –> xanthine –> uric acid

AMP –> IMP –> inosine –> hypoxanthine –> xanthine –> uric acid

Question 2

what enzyme do other animal species have that prevents them from getting gout

Answer 2

uricase (breaks down uric acid into allantoin)

Question 3

what enzyme converts free adenine to AMP

Answer 3

adenine phosphoribosyl transferase (APRT)

Question 4

what enzyme converts hypoxanthine to AMP and guanine to GMP (in the salvage pathway)

Answer 4

hypoxanthine-guanine phosphoribosyl transferase (HGPRT)

Question 5

absence or deficiency in HGPRT results in

Answer 5

lesch-nyhan syndrome

Question 6

what can cause urate overproduction in secondary hyperuricemia

Answer 6

• excessive purine intake

- tumor lysis syndrome

Question 7

what are the recommended NSAIDs for acute gout

Answer 7

• naproxen
• indomethacin
• celecoxib

Question 8

in acute gout, when do you give glucocorticoids

Answer 8

if only a few joints or NSAIDs and colchicine are contraindicated

Question 9

MOA and effects of colchicine

Answer 9

blocks formation of microtubules

leads to inhibition of leukocyte migration and phagocytosis

Question 10

indications colchicine

Answer 10

used in acute gout pts with NSAID intolerance or absolute contraindications to NSAIDs

Question 11

administration, half life, and metabolism of colchicine

Answer 11

administration: oral

half life: 27-31 hours

metabolism: CYP3A4 and excreted by kidneys

Question 12

colchicine is contraindicated in pts with _____

Answer 12

renal or hepatic impairment

Question 13

adverse effects colchicine

Answer 13

GI distress (N/V/D)

Question 14

MOA and effects of allopurinol

Answer 14

competitively inhibits xanthine oxidase

hypoxanthine and xanthine are both excreted

Question 15

indications allopurinol

Answer 15

recurrent gout

cancer-chemo induced hyperuricemia (tumor lysis syndrome)

Question 16

administration, half life, and metabolism of allopurinol

Answer 16

administration: oral

half life: 15 hours

metabolism: eliminated by kidneys

Question 17

lower doses of allopurinol need to be given in patients with _____

Answer 17

renal impairment

Question 18

adverse effects allopurinol

Answer 18

• skin rash
• can trigger acute gout attack
• N/V
• increased liver enzymes
• Stevens-johnson syndrome

Question 19

MOA and effect febuxostat

Answer 19

non-competitive inhibitor of xanthine oxidase

hypoxathine and xanthine are both excreted

Question 20

indications febuxostat

Answer 20

recurrent gout in patients who cannot tolerate allopurinol

also cancer-chemo induced hyperuricemia (tumor lysis syndrome)

Question 21

administration and half life of febuxostat

Answer 21

administration: oral

half life: 5-8 hours

Question 22

downsides of febuxostat

Answer 22

VERY expensive

Question 23

MOA and effects of pegloticase

Answer 23

recombinant mammalian uricase –> covalently attaches to methoxy polyethylene glycol

converts uric acid to the far more soluble allantoin

Question 24

indications pegloticase

Answer 24

treatment of chronic gout in those unable to receive conventional therapy

Question 25

administration of pegloticase

Answer 25

IV every 2 weeks

Question 26

adverse reactions pegloticase

Answer 26

infusion reactions (fever, chills, rash, angioedema, bronchospasm, hypotension)

Question 27

MOA rasburicase

Answer 27

nonpegylated recombinant uricase

Question 28

indications rasburicase

Answer 28

prevention of acute uric acid nephropathy due to tumor lysis syndrome in pts with high risk lymphoma or leukemia

Question 29

MOA and effects of probenecid

Answer 29

blocks urate reabsorption more than urate secretion

increases fractional excretion of urate and decreases plasma urate concentration

Question 30

indications probenecid

Answer 30

reduces urate levels in underexcreters with GFR > 60

Question 31

administration and half life probenecid

Answer 31

administration: oral

half life: 6-12 hours

Question 32

adverse effects probenecid

Answer 32

increases risk of kidney stones

may cause gouty arthritis flare