Pharm of DMARDs (Fitz)

Question 1

MOA for methotrexate (MTX)?

Answer 1

inhibits DHF

anti-proliferative and immunosuppressive

Question 2

MOA of hydroxychloroquine and sulfasalzine?

Answer 2

non-specific

anti-proliferative and immunosuppressive

Question 3

MOA of Leflunamide?

Answer 3

inhibit Dihydroorotate Dehydrogenase

anti-proliferative and immunosuppressive

Question 4

the frontline DMARD of choice for mild to moderate RA is ___

Answer 4

low dose MTX

A pro-drug, becomes most active when polyglutamated within cells (MTX-(glu)n. Takes ~25-30 wks to reach stedy-state –> time to achieve plateau effect of clinical response with MTX

Question 5

When MTX inhibits DHFR, what downtream products are not synthesized?

Answer 5

it disrupts purine and pyrimidine synthesis

This is Anti-Proliferative

Question 6

When MTX inhibits AICAR-TFase, what products accumulate? what is the effect?

Answer 6

Adenosine –> accumulation of adenosine exerts anti-inflamm effects by binding to purinergic/adenosine receptors

Question 7

consequence of MTX administration in pt with kidney dysfunction (decreased GFR)?

Answer 7

rise in serum levels of MTX and rise in toxic/adverse events

80-90% of MTX is cleared via the kidneys

Question 8

Potentially life-threatening toxicities of MTX?

Answer 8

• Hepatotoxicity-do LFTs
• Pulmonary damage-hypersensitivity
• Myelosuppression

these are more common with high-dose tx for cancer, but do occur with low-dose tx

Question 9

all pts receiving MTX should take __ daily or weekly __ to prevent hematologic side effects

Answer 9

1 mg folic acid
OR
weekly Folinic acid (leucovorin)

Question 10

what TF is repressed with glucocorticoids?

Answer 10

repress NF-kB TF

Question 11

why give pulse glucocorticoid tx in RA?

Answer 11

Tx acute flares

A therapeutic bridge between initiation of and response to DMARDs

adverse: osteoporosis, DIABETOGENIC

Question 12

this biologic is 100% humanized soluble TNF receptor, acts as a receptor decoy, given 1x weekly subQ

Answer 12

Etanercept

Question 13

this monoclonal Ab drug inhibits TNF, given at 0,2,6,8 weeks/IV

Answer 13

infliximab

Question 14

this monoclonal Ab drug inhibits TNF, given 2 weeks, sub Q

Answer 14

adalimumab

Question 15

this IL-1 receptor antagonist is given daily every 6 hrs

Answer 15

Anakinra

Question 16

considering the safety of anti-TNFalpha agents, these all increase the risk of __

Answer 16

serious infx, lymphomas, and other malignancies

• TB
• opportunistic infx: histo, listeriosis, coccidiodomycosis, pneumocystis carinii pneumonia
• non-opportunistic infx

Question 17

__ is a PEGylated humanized Ab Fab’ fragment of TNF-a monoclonal Ab

Answer 17

Certolizumab pegol

Question 18

__ is a human monoclonal Ab that binds to human TNFa, subQ 1x/month

Answer 18

Golimumab

Question 19

__ is approved to tx adults with moderately to severely activa RA who have an inadequate response to, or who are intolerant of, MTX

Answer 19

Tofacitinib (Xeljanz)

Question 20

__ is an oral Janus Activated Kinase inhibitor that is a targeted immunomodulator and disease-modifying therapy for RA

Answer 20

Tofacitinib

Question 21

what should you not do while being tx with or after you stop Tofacitinib?

Answer 21

do not have any vaccines w/o doc approval

Tofacitinib may lower bodys resistance and vaccine may not work or you may get infx

-avoid contact w/persons living in household who receive live virus vaccines b/c there is a chance they can pass virus on to you.