Gout; OA; RA/ pool/med chem

Question 1

List 2 important transported for Uric acid reabsorption

Answer 1

URAT-1 and GLUT 9

Question 2

Which part of kidney is important for uric acid reabsorption?

Answer 2

proximal convoluted tube (PCT)

Question 3

What 2 compounds inhibit uric acid reabsorption?

Answer 3

Probenecid & Benzbromarone

Question 4

What is the function of Uricase (Pegloticase)?

Answer 4

Convert UA to Allantoin

Question 5

What is the product of the oxidation of uric acid catalyzed by uricase?

Answer 5

Allantoin

Question 6

Which form, UA or urate, id predominant at pH 7.4?

Answer 6

urate

Question 7

Describe the association between gout and uric acid

Answer 7

increase in UA levels –> form insoluble crystals –> increased inflammation –> gout

Question 8

List 2 XO inhibitors

Answer 8

Allopurinol
Febuxostat

Question 9

Understand the relationships among Xanthine, Hypoxanthine, uric acid and Allantoin

Question 10

List 3 uric-acid-lowering therapies

Answer 10

UA synthesis inhibitors
UA reabsorption
UA elimination

Question 11

What re the primary drugs recommended as first-line treatment for hyperuricemia?

Answer 11

XO inhibitor

Question 12

What 2 bases in nucleic acid are purine?

Answer 12

Adenine and Guanine

Question 13

What is the function of Xanthine oxidase?

Answer 13

uric acid synthesis

Question 14

Uric acid is a weak acid because…

Answer 14

it can release a proton

Question 15

First-line rate-lowering therapy

Answer 15

Xanthine Oxidase inhibitors

Question 16

XO inhibitor MOA

Answer 16

inhibit uric acid synthesis

Question 17

second-line urate lowering inhibitors

Answer 17

Benzbromarone
Probenecid
Pegloticase

Question 18

Benzbromarone MOA

Answer 18

increase renal urate excretion

Question 19

Probenecid MOA

Answer 19

increase renal urate excretion

Question 20

Pegloticase MOA

Answer 20

UA degradation

Question 21

which XO inhibitor is non-purine-like? Allopurinol or Febuxostat

Answer 21

Febuxostat

Question 22

Allopurinol is excreted…

Answer 22

by the kidney

Question 23

Febuxostat is metabolized…

Answer 23

in the liver

Question 24

How many oxygen atoms are in UA?

Answer 24

3

Question 25

Which metal atom is the active site of XO?

Answer 25

molybdopterin (MO)

Question 26

What is NOT a good treatment of hyperuricemia?

Answer 26

inhibiting UA oxidation

Question 27

Which compound is NOT an XO inhibitor? -Febuxostat -Allopurinol -Oxypurinol -Allantoin

Answer 27

Allantoin

Question 28

Which compound is an analogous of hypoxanthine and xanthine? -febuxostat -allopurinol -benzbromarone -probenacid

Answer 28

Allopurinol

Question 29

Which medication has multiple significant drug interactions with commonly used drugs like NSAIDs?

Answer 29

Probenecid

Question 30

Which transporters do Probenecid inhibit?

Answer 30

URAT 1 and GLUT 9

Question 31

Name the non-selective COX inhibitors

Answer 31

Diclofenac Flurbiprofen Ibuprofen Indomethacin Naproxen Nabumetone

Question 32

T/F The COX pathway of arachidonate metabolism produces prostaglandins

Answer 32

true

Question 33

Which COX isoform is induced during inflammation and tends to facilitate the inflammatory response? COX-1 or COX-2

Answer 33

COX-2

Question 34

Name an NSAID that is ketone prodrug and is metabolized to the acidic active drug?

Answer 34

Nabumetone

Question 35

biologic DMARDs - Tumor Necrosis factor Inhibitors -

Answer 35

Etanercept (Enbrel, Erelzi) Infliximab (Remicade) Adalimumab (Humira) Golimumab (Simponi and Simponi ARIA) Certolizumab pegol (Cimzia)

Question 36

What do TNF inhibitors (TNFi) block?

Answer 36

both forms of TNF-a

Question 37

AE of TNF-a-blocking agents

Answer 37

- TNF-a blocking agents increase the risk of bacterial infections and macrophage-dependent infections (including tuberculosis, fungal, and other opportunistic infections) are increased - associated w/ rick of HBV reactivation - increase the risk of skin cancers- including melanoma - Rare cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia

Question 38

Rituximab (RTX) MOA

Answer 38

chimeric monoclonal antibody that targets CD20 B-lymphocytes through cell-mediated and complement-dependent cytotoxicity and stimulation of cell apoptosis

Question 39

Rituximab AE

Answer 39

- assoc with reactivation of Hep B - about 30% of pts develop rash with the first RTX dose