Treatment of Rheumatoid Arthritis Flashcards
- block the cylo-oxygenase enzymes (COX 1and 2)- less prostaglandin synthesis (less symptoms of inflammation)
- Cox-1 is constitutively expressed
- COX-2 is amplified and sustained in response to inflammation
- prostaglandins cause increased blood flow, pain, enhanced vascular permeability, fever etc
NSAIDs
what are common side effects of NSAIDS based on systems? GI, Renal, CV, CNS, Derm, Heme,
- GI: gastritis, ulcers, hepatitis, pancreatitis
- renal: reduced GFR, edema, kidney failure
- CV: MI, hypertension
- CNS: headache, dizziness, aspetic meningitis
- derm: rashes, photosensitivity
- heme: bruising
others: asthma, can also have drug interaction with warfarin
- temporary treatment until other medication have effect
- always affective
- use lowest effective dose, shortest duration
- injections: intra-articular for an active joint, local injections- tendinitis, carpal tunnel syndrome, rheumatoid nodules, I.M injections to stop flare
- dose: prednisone 10-30mg a day
- triamcinolone acetonide 40-120mg IM
Corticosteroids
side effects of corticosteroids?
chronic treatment can lead to
- osteoporosis
- weight gain
- diabetes
- infections
Brief treatment
- few side effects
- if high dose: elevated blood sugar, insomnia, steroid psychosis
which medications are DMARDs
- hydroxycholorquine
- sulfasalazine
- methotrexate
- Leflunomide
what medications are JAK inhibitors
- tofacitnib
- barictinib
- upadacitinib
- which medications or TNF-alpha inhibitors?
- entanercept
- infliximab (infusion every 8 weeks)
- adalimumab (injection every 2 weeks)
- golimumab (injection montly of infusion every 8 weeks)
- certoizumab (injection every 2 weeks)
- enbrel
- remicade
- humira
- cimzia
which medications are IL-6 inhibitors?
- tocilizumab (injection every 1-2 weeks or infusion every 4 weeks)
- actemra
- sarilumab (injection every 2 weeks)
which medication is Anti B cell
rituximab (two infusions 2 weeks apart, repeat as needed > 6 months)
rituxan
- Analog of folic acid
- blocks dihydrofolate reductase and other enzymes
- inhibits purine and pyrimidine syntehsis
- increases extracellular adenosine
- decreases activity: T-cells, B-cells, monocytes
- Can be given orally or as an injection (always with folic acid 1mg a day)
- peak serum levles within 1-2 hours after dosing
- 6 months to full effect
Methotrexate
adverse reactions of methotrexate?
- usually very well tolerated
- GI: nausea, mouth sores, anorexia
- hepatic: focal necrosis, cirrhosis
- hematopoetic: cytopenias, macrocytosi
- pulmonary: acute interstial pneumonia
- CNS: headaches, fatigue
- teratogenic
- Monitor CBC, transaminases, creatinine every 3 months
- Decreases T and B cell proliferation
- decreaes immunoglobulin synthesis
- Active metabolite is tightly bound to plasma protein (steady state reached in 7 week)
- very long half life cholesytramine can be used to speed up elimination, tetratogenic
- clinical use: efficacy similar to MTX
- Side Effects: diarrhea rare- HTN, anorexia, neuropathy
Leflunamide
- blocks toll like receptors
- pharmacology- extensively tissue bound,, long half-life (40 days) , very delayed action (6 months)
Hydroxycholoroquine
colonic bacteria metabolize
* sulapyridine
* 5-aminosalicylic acid
Mechanism of action
- inhibits IL-2 induced T-cell proliferation
- changes B lymphocyte function
- reduces pro-inflammatory cytokines
Sulfasalazine
side effects of hydroxychloroquine
- nausea-transient
- rash- early
- pigment changes
- myopathy, cardiomyopathy
- retinopathy- related to cumulative dose (baseline visual field exam and then yearly from the 5th year)
- headache
- depression
side effects of sulfasalazine
- nausea
- rash- early
- SJS (rare)
- bone marrow
- headache
Side effects of TNF inhibitors
- Infections: mild viral or bacterial infections
- drug reactions: infliximab- chills/headache
adalimumab/etanercept/golimumab/certilizumab: injection site irritation, rash
risks associated with TNF inhibtors
Serious infections
- bacterial
- fungal
- TB
reactivation of latent infections
- screen before treatment: TB, hepatitis B and C
Exacerbation of COPD (possible contraindication)
Exacerbation of CHF (contraindication)
Anaphylaxis
autoimmunity
bone marrow failure
- Inhibitors of janus kinases
- blocks intracellular pathways following membrane activation
- Side effects: infections- herpes zoster, abnormal liver function tests, neutropenia, elevated lipids, elevated creatinine, DVT, possibly increased risk for malignancy: solid cancers and lymphoma
Tofacitinib, baricitinib, upadacitinib
- blocks co-stimulatory signal for T-cell activation
- used alone or in combination with methotrexate or other DMARDs
- infused monthly
- injected 125mg weekly
- side effects (rare infusion reactions, infections)
Abatacept
Indications
- active RA, secondor third line treatment
adverse reactions
- elevated liver tests
- hyperlipidemia
- increased risk of infections
II-6 inhibition
what are the outcomes of being on biologic therapy?
fewer hospitalizations
reduced overall mortality
reduced incidecne of CVD
fewer hip and knee replacements
higher workforce retention
what vaccines are safe on immunosuppressants?
- HBV
- pneumococcus
- influenza
- meningitis
- HSV (shingrix)
- Covid 19
what vaccines are NOT safe during immunosuppression?
- yellow fever
- rotavirus
- HZV
- bcg
- MMR
- typhoid
- polio
Which medication reduce the benefit of vaccines?
- steroids
- rituximab
- and high dose prednisone
