RA drugs: Fitz

Question 1

what are the disease modifying anti Rheumatic Drugs (DMARDS)

Answer 1

• methotrexate: inhibit dihydrofolate reductase
• Hydroxychloroquine
• Sulfasalazine
• Leflunamide: inhibits dihydroorotate dehydrogenase

Question 2

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

Answer 2

low dose methotrexate

Question 3

time to reach steady state for methotrexate

Answer 3

• needs to become polyglutamated

- takes 25-30 weeks

Question 4

What does polyglutamated methotrexate inhibit in cells?

Answer 4

• DHFR: Disrupts purine and pyrimidine synthesis. anti proliferative and immunosuppressive
• and AICAR TFase

Question 5

what does inhibiting AICAR TFase do?

Answer 5

builds up adenosine which can be anti inflammatory

Question 6

how do you increase bioavailability of MTX

Answer 6

give same dose parenterally instead of orally

Question 7

Toxicities of MTX

Answer 7

• Hepatotoxicity: do liver function tests
• Pulmonary damage: hypersensitivity
• Myelosuppression: more common with high dose therapy for cancer but do occur sometimes with low dose

Question 8

what should all pts taking MTX also take

Answer 8

• folic acid 1 mg daily

- or weekly folinic acid (leucovorin) to prevent hematologic side effects

Question 9

what happens with withdrawal of MTX

Answer 9

flare of RA within 3-6 weeks

Question 10

Describe the mechanism and use of glucocorticoids in RA

Answer 10

• repress transcription of genes encoding inflammatory cytokines (TNFa, IL-1) and COX-2 (REPRESS NFkB transcription factor
• pulseglucocorticoid therapy in RA is limited to: 1: treatment of acute flares. 2: a therapeutic bridge b/t the initiation of and response to DMARDS

Question 11

adverse effects of glucocorticoids

Answer 11

• osteoporosis

- diabetogenic

Question 12

corticosteroids used and routes of administration

Answer 12

• Prednisone: oral
• Methylprednisolone: IM
• Triamcinolone and Hexacetonide: intra articular

Question 13

what is used for moderate to severe RA in combo with low dose MTX

Answer 13

biological agents

Question 14

Describe the biological agents used

Answer 14

• Etanercept: soluble TNF receptor
• Infliximab and Adalimumab: Anti-TNF monoclonal antibodies
• Anakinra: inhibits IL-1
• Certolizumab pegol: pegylated humanized antibody
• Golimumab: monoclonal antibody

Question 15

onset of anti TNF agents?

onset of IL-1 antagonists

Answer 15

• 2-4 weeks

- 4-6 weeks

Question 16

What are the risks of using ALL anti-TNF agents

Answer 16

• increase risk for serious infections, lymphomas, and other malignancies
• Tb
• opportunistic infections (eg. histo, listeria, cocci, pneumocystic carini)

Question 17

what is used to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate resonse to, or who are intolerant of MTX

Answer 17

Tofacitinib

Question 18

MAO of Tofacitinib

Answer 18

-oral JAK inhibitor . . . an intracellular signaling pathway

Question 19

what is the caution with Tofacitinib

Answer 19

• Don’t get vaccines . .you might get the infection
• don’t be around those that got vaccine
• measles, mumps, flu, polio, rotavirus, rubella