Fitzy: Pharmacology of Rheumatoid Arthritis

Question 1

What kinds of drugs do we use for RA?

Answer 1

-immunosuppressive drugs because it’s an autoimmoune rxn

Question 2

Biologyical agents used

Answer 2

• Anti TNGa

- Anti IL-1 antibodies/antagonists

Question 3

Signal modulation

Answer 3

-Janus kinase inhibitor

Question 4

Disease modifying Rheumatic drugs (DMARDS)

Answer 4

• methotrexate: inhibits Dihydrfoloate reductase
• Hydroxychoroquine
• sulfasalzine
• leflunamide: inhibits dihydroorotate dehydrogenase

Question 5

What is the frontline DMARD of choice for mild to moderate RA?

Answer 5

-Low dose methotrexate (MTX)

Question 6

When does MTX become most active?

Answer 6

• when it gets polyglutamated within cells
• takes 25-30 weeks to reach steady state
• takes time to achieve a plateau effect of clinical response with MTX

Question 7

What does MTX (glu)n inhibit?

Answer 7

• AICAR TFase: so no more F-AICAR

- DHFR

Question 8

If AICAR can’t get turned into F-AICAR, what happens to it?

Answer 8

• it turns into adenosine
• then, that activates purinergic/adenosine G ptn receptors… anti inflammatory effect
• this is the anti inflammatory part

Question 9

What is the result of DHFR being suppressed?

Answer 9

• no more THF production
• so no more thymidine and purines… they get depleted
• this is the anti proliferative part

Question 10

what is the better route for administration of MTX?

Answer 10

-parenteral because it increases bioavailabitily

Question 11

what do we have to keep track of in the patient if we are going to use MTX?

Answer 11

• their renal function
• 80-90% of MTX is cleared via kidneys
• it will build up…. adverse effects… booo

Question 12

What toxicities are associated with MTX?

Answer 12

• hepatotoxicity: so do liver function tests
• pulmonary damage
• myelosuppression
• *this is more common with high dose therapy for cancer, but do occur with low dose therapy

Question 13

What else should all people taking MTX take?

Answer 13

• folic acid daily
• or folinic acid weekly
• to prevent hematologic side effects

Question 14

What does withdrawal of MTX lead to?

Answer 14

• flare of RA within three to six weeks

- clearance of MTX(glu)n

Question 15

What do glucocorticoids do?

Answer 15

• repress transcription of genes encoding inflammatory cytokine and COX-2
• *** so the repress the NFKB transcription factor

Question 16

When should we use pulse glucocorticoid therapy?

Answer 16

-treatment of acute flares of RA

Question 17

adverse effects of glucocorticoids

Answer 17

• osteoporosis

- diabetegenic (bolded)

Question 18

What are the different corticosteroids we can use?

Answer 18

• Prednisone: oral
• Methylprednisolone: IM
• Traimcinolone and hexacetonide: intra-articular

Question 19

What two cytokine things are involved with RA?

Answer 19

• TNF alpha

- IL-1

Question 20

What is the 100% humanized solube TNF receptor?

Answer 20

• etanercept
• binds to TNF…
• “CEPT” for reCEPTor

Question 21

Anti TNF monoclonal antibodies

Answer 21

• infliximab: mouse TNF binding and human IgG1

- Adalimumab (100%) humanized: human TNF binding and human IgG1

Question 22

What is Anakinra?

Answer 22

• inhibits IL-1

- receptor antagonist

Question 23

What are the safety issues with anti-TNF alpha agents?

Answer 23

• increase the risk for serious infections
• TB!!!
• pneumocytic carinii if CD4 count is <100

Question 24

what is Certolizumab pegol?

Answer 24

-a pegylated humanized antibody Fab fragment of tumor necrosis factor alpha monoclona antibody

Question 25

What is golimumab?

Answer 25

• human monoclonal antibody that binds to human tumor necrosis factor alpha (TNF a)
• sq 1x per month

Question 26

What do we give adults who have RA if they have an inadequate response to, or are intolerant of, MTX?

Answer 26

-Tofacitinib

Question 27

What is Tofacitinib?

Answer 27

• an oral Janus activated kinase (JAK) inhibitor that is a targeted immunomodulator and disease-modifying therapy for RA
• it’s unique because it has an intracellular target: JAK

Question 28

What do we have to be careful with when using Tofacitinib?

Answer 28

-don’t have any immunizations without your doctor’s approval