DMARDS Flashcards
Sequence of Disease process in RA
- the first event is probably antigen-dep activation of T cel..s
- DC & tissue MOx & synovial cellsproduce IL-1 & TNFa
- IL-1: stim syn of cytokines to promote jt. destruction like PGE2, NO & MMPs
IL-1 endogenous pyrogen
Augments activation T &B cells & cause MOx to release proteolytic enz
Stim. cartilage destruction
Stim integrins, selectins
TNFa
Stim hematopoietic cells, APCs, B cells, Ab production, germinal cell formation, cartilage destruction
HEV
present in 2nd lymphoid tussies
Recruitment of circulating lymphocytes from blood into joint may occur
Infliximab
Remicade
1. human/mouse IgG1 monoclonal antibody
2. has Fc region & binds TNFa
3. IV infusion w/ methotrexate (oral) but takes weeks
4. Infusion rxn= fever, chils, pruritis & rash
5. Use: Crohn’s disease, UC, RA, ankylosing spondylitis, psoriatic arthritis, IBD
6. MOA: binds to TNF a & prevents interaction
7. Adverse: common abdom pain, fatigue, headache.
Hypersensitivity
TB
T-cell lymphoma
Heart fail
Adalimumab
Humira
1. fully human monoclonal IgG1 antibody against TNFa
2. not foreign!!
3. SC every 2 weeks
4. Use: ankylosing spondylitis, Crohn’s, psoriasis with arthropathy, RA
5. MOA: block interaction of TNF a with TNFa R on cell surface.
Red CRP, ERS, Il-6, MMP 1& 3.
6. BB: TB or other opportunistic infections some fatal.
7. Adverse: exacerbate chronic CHF, serious infections, lupus-like syndrome
Etanercept
Enbrel
1. solub recombo human TNF R fusion prot
2. Binds TNFa & inactivates it.
3. SC injection/week
4. Use: RA, psoriatic arthritis, juvenile arthritis
5. MOA: inhibit binding of TNFa & TNF B to their R, decrease inflamm actions of TNFa
6. Adverse: injection site rxn, autoantibody form, serious infection, hypersenstivity, increased risk of cancer.
C/I: documented hypersensitivity, sepsis, concurrent live vaccines. NOT FOR PTS WITH MS!
Anakinra
(Kinert)
- recombo IL-1 R antagonist
- Anti inflamm cytokine
- Use: RA
- Adverse: headache, GI distress, injection site rxn is strong
- Serious adverse effects: infections, decrease in WBC, antibody form to Anakinra
Penicillamine
- give if all other drugs fail with active RA
- MOA:?
- oral, take months to take effect. Need to measure plts, urinalysis, CBC every 2-4 wks
- Adverse: cutaneous lesions, blood dyscarsias- BM suppression, autoimmune syndrome, taste disturbance bitter taste, proteinuria, may be immunogenic & produce hypersensitivity rxn.
Severe dyspnea, MG, teratogen. - C/I: Goodpasture’s
Hydroxychloroquine/chloroquine
- 2nd line drugs
- Use: RA & SLE
- MOA: drug suppresses responsivness of T lymphocytes to mitogens
decrease leukocyte chemotaxis
stabilize lysosomal mem
inhibit DNA & RNA syn
Traps free radicals so reduce ox rxns associated w/ deteriorating bone - Oral, takes 4-12 wks
- Adverse: dermatitis, myopathy, reversible corneal opacity, GI irritation, nightmares
*irrev retinal degen dose & freq related. Need ophthalmic exams every 6 months. Night blindness, blurred vision, missing or blanched out A of central/peripheral fileds, light flashes & streaks & photophobia
Sulfasalazine
(Azulfidine)
1. Use: prodrug to treat UC, IBD & RA.
Oral, active metabolite: 5 aminosalicylic acid (mesalamine) and sulfapyridine
2. MOA: anti inflamm actions are due to I of COX in gut w/ reduced prod PG
3. Adverse: nausea, vomit, diarrhea & anorexia
Rash & serum sickness
Leukopenia, thrombocytopenia, alopecia, stomatitis & elevated hepatic enz.
Methotrexate
- cytotoxic drug
- reduce RA & slows rate of change
- @ much lower dose than cancer
- oral, once a week or every other week. W/ folate
- Adverse: long term nausea, vomit, diarrhea, anorexia
Leukopenia
MTX lung- hypersensitivity rxn. folinic acid as rescue
Azathiprine
as immunosuppressant
Leflunomide
(Arava)
1. use: moderate to sever RA & psoriatic arthritis
2. MOA: inhibit pyrimidine syn as it inhibits dihydroorotate dehydrogenase, rate limit step for de novo pyrimidine syn
Inhibits T & B lymphocytes prolif!
3. Adverse: GI toxicity, elevate transaminase levels, rash & allergic rxn, reversible alopecia, headache, teratogen, renal impair, cytopenias.
Cyclosporine
immunosuppressant
