5. Disease Modifying Anti-Rheumatic Drugs Flashcards
Drugs for Rheumatoid Arthritis
Pain/Inflam: acetaminophen/NSAIDs/glucocorticoids
Tradish Disease Modifying Antirheumatic drugs (DMARDs): methotrexate, hydroxychloroquine, sulfasalazine, leflunomide
Biologic DMARDs
TNFA Block: entanercept, adalimumab, infliximab
BCell Depleter (CD20Ab): rituximab
TCell Activation Inhib: abatacept
IL-6 Receptor mAb (tocilizumab)
JAK3 Inhib: tofacitinib
Recombinant IL1 Antagonist:?
Anakinra
Goals of RA is to stop inflammation, relieve symptoms and prevent joint and organ damage, nonpharmacologic treatments for RA include education, rest, exercise, physical therapy, occupational therapy, nutrition and dietary therapy, bone protection, cardiovascular risk reduction and?
Vaccinations- pts should NOT* receive live vaccines
RA- NSAIDs are first choice drugs to relieve anti-inflam action and pain relief, acetaminophen is added for pain, opioids are not used, either Aspirin, celecoxib or what is MC used, but they are NOT disease modifying, just take care of the sx?
Naproxen
What RA drug binds glucocorticoid receptor (GR) complexing with NF-kB and AP1 trancription factors is the major indirect mechanism for immunosuppression, it also activates lipocortin which inhibits PLAs, it suppresses many ILs and IFN-Y and causes lymphocyte apoptosis, suppresses neutrophil migration and decreases eosinophils, treats autoimmune diseases such as RA and relieves pain and inflamm while waiting for DMARD effects (since they take 6 weeks to work), also treats flares, given PI, IM or Intra articular?
Glucocorticoids such as Prednisone (pro drug, no effects till converted to prednisolone in liver)
Note beta/dexa/methasone and triamcinolone all have Fluorine added which INCREASES potency and 1/2 life
Glucocorticoid is used in sicker patients with active RA, prednisone is frequently added for a *SHORT period to minimize dz activity while awaiting clinical response to slower acting DMARD, use for LESS than 1 month, and they are only effective for less than 6 months, should not be given chronicall but low dose with DMARDs is ok such as?
<5mg/day can be taken without sig SE, but there is NO reduction in disease progression
Mild RA is less than 5joints enflamed, ESR normal and normal CRP, no extraarticular disease, no evidence of erosions, low levels of disease activity and LACK rheumatoid factor or abs to CCP, treatment of early or mild RA includes?
DMARD Monotherapy
Moderate RA is >5 joints inflamed, increased ESR and CRP, positive RF and ab to CCP, evidence of inflammation on radiography, joint space narrowing and small peripheral erosions- treated with combo of tradition (nonbiolofic) DMARDs or (TNF* or non-TNF or tofacitinib), which what can/is added to ALL of them?
Methotrexate
What is a non-biologic DMARD which inhibits dihydrofolate reductase causing thymineless death (pulse), undergoes polyglutamation which accumulates in cells over many weeks and blocks thymidylate synthase and 5-aminoimidazole 4 carboxamide ribonucleotide AICAR transformylase, resulting in AICAR accumulation leads to adenosine efflux which binds to purinergic GPCRs on cell surface to exert anti-inflam effects?
Methotrexate (MTX)
Methotrexate (MTX) acts faster than DMARDS with effects in 3-6 weeks, works for 80% pts, drug FIRST CHOICE in RA due to efficacy, relative safety and low cost and extensive use, often continued when patient is on biologic, admin q week either orally or injection, drug persists for several weeks, low doses*, need folate supplement, causes fetal death and at high doses causes BM suppression, hepatic fibrosis, GI ulceration and?
Pneumonitis
What is a non-biologic DMARD is lipophilic weak base and accumulates in lysosomes to increase pH of lysosome from 4-6, higher pH in these antigen presenting cells limits the association of peptides with class II MHC molecules, slows* disease progression but onset takes 3-6 months?
Hydroxychloroquine
Hydroxychloroquine is used as an antimalarial, could be first choice for RA but lack poor prognostic features, combined with methotrexate, used in SLE, orally active and 1/2 is 23 days, so need to use loading dose, SE: RETINAL DAMAGE with high doses, what is this drug considered to be safe for?
Safe during pregnancy!!
What is a non-biologic DMARD MOA is not understood, it is metabolized to sulfapyridine= is the active moiety in pt with RA and 5ASA, comparable to if not more effective than hydroxchloroquine, benefits in 1 month, for RA alone or with hydroxy and or MTX = TRIPLE therapy, okduring preg but less studied, SE: GI, inhibits folic acid, sulfa drug*= reactions?
Sulfasalazine (also used in chrons because of 5ASA metabolite)
What is a non-biologic DMARD causes inhibition of dihydroorotate dehydrogenase to block the synthesis of pyrimidine rUMP, inhibits T cell proliferation*, and has anti inflam effects, it is an alternative to MTX (2nd choice), can be used in combo with MTX, PO admin with 16.5 day 1/2 life so need loading doses, MC adverse effects are diarrhea, resp infection, alopecia, rash nausea, heptatoxic steven johnson?
Leflunomide - worse SE so use MTX instead
Biologic DMARDs can be combined with non-biologic DMARDS BUT NEVER combine two biologics, - they usually have faster onset (2-4weeks) high rate of response but are more expensive and are at an increased risk for?
Severe adverse effects
The main proinflammatory cytokines that result in RA include IL6, TNFa which is released from Th17/Th1 and APC cells, along with IL1b and IL23, what are the two cytokines that are released and cause fibrosis and are anti inflammatory?
TNFb
IL10
