Fitzy: Pharmacology of Rheumatoid Arthritis Flashcards
What kinds of drugs do we use for RA?
-immunosuppressive drugs because it’s an autoimmoune rxn
Biologyical agents used
- Anti TNGa
- Anti IL-1 antibodies/antagonists
Signal modulation
-Janus kinase inhibitor
Disease modifying Rheumatic drugs (DMARDS)
- methotrexate: inhibits Dihydrfoloate reductase
- Hydroxychoroquine
- sulfasalzine
- leflunamide: inhibits dihydroorotate dehydrogenase
What is the frontline DMARD of choice for mild to moderate RA?
-Low dose methotrexate (MTX)
When does MTX become most active?
- 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
What does MTX (glu)n inhibit?
- AICAR TFase: so no more F-AICAR
- DHFR
If AICAR can’t get turned into F-AICAR, what happens to it?
- it turns into adenosine
- then, that activates purinergic/adenosine G ptn receptors… anti inflammatory effect
- this is the anti inflammatory part
What is the result of DHFR being suppressed?
- no more THF production
- so no more thymidine and purines… they get depleted
- this is the anti proliferative part
what is the better route for administration of MTX?
-parenteral because it increases bioavailabitily
what do we have to keep track of in the patient if we are going to use MTX?
- their renal function
- 80-90% of MTX is cleared via kidneys
- it will build up…. adverse effects… booo
What toxicities are associated with MTX?
- 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
What else should all people taking MTX take?
- folic acid daily
- or folinic acid weekly
- to prevent hematologic side effects
What does withdrawal of MTX lead to?
- flare of RA within three to six weeks
- clearance of MTX(glu)n
What do glucocorticoids do?
- repress transcription of genes encoding inflammatory cytokine and COX-2
- *** so the repress the NFKB transcription factor
When should we use pulse glucocorticoid therapy?
-treatment of acute flares of RA
adverse effects of glucocorticoids
- osteoporosis
- diabetegenic (bolded)
What are the different corticosteroids we can use?
- Prednisone: oral
- Methylprednisolone: IM
- Traimcinolone and hexacetonide: intra-articular
What two cytokine things are involved with RA?
- TNF alpha
- IL-1
What is the 100% humanized solube TNF receptor?
- etanercept
- binds to TNF…
- “CEPT” for reCEPTor
Anti TNF monoclonal antibodies
- infliximab: mouse TNF binding and human IgG1
- Adalimumab (100%) humanized: human TNF binding and human IgG1
What is Anakinra?
- inhibits IL-1
- receptor antagonist
What are the safety issues with anti-TNF alpha agents?
- increase the risk for serious infections
- TB!!!
- pneumocytic carinii if CD4 count is <100
what is Certolizumab pegol?
-a pegylated humanized antibody Fab fragment of tumor necrosis factor alpha monoclona antibody
What is golimumab?
- human monoclonal antibody that binds to human tumor necrosis factor alpha (TNF a)
- sq 1x per month
What do we give adults who have RA if they have an inadequate response to, or are intolerant of, MTX?
-Tofacitinib
What is Tofacitinib?
- 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
What do we have to be careful with when using Tofacitinib?
-don’t have any immunizations without your doctor’s approval
