|
Home > Preview
The flashcards below were created by user
jgiantess
on FreezingBlue Flashcards.
-
Methotrexate
- MoA:
- - Inhibit of aminoimidazolecarboxamide (AICAR) transformylase
- (10-formyl THF + AICAR -x-> THF + FAICAR)
- Accum AICAR: increase adenosine release @ sites of inflammation, increase inhibition of inflammation (adenosine A2 receptors) =action in autoimmune disease.
- - affects polymorphonuclear chemotaxis
- - Also inhibit dihydrofolate reductase , and thymidylate synthetase (angiogenesis and affects lymphocyte/mac function)
- - Anti-inflam: inhibits cytokine production, purine biosynthesis; stimulates adenosine release.
- - Decreased rate of appearance of new RA erosions
- - Improves survival (only drug CVD)
- - 2-3 weeks onset (use NSAIDs to bridge)
- PK:
- A: F ~70%
- D: 35-50% PB
- M: hydroxylated to less active
- Parent cpd+ metabolite
- metab’d further into
- polyglutamated derivs
- intracellularly.
- E: renal: 70-80% unchanged
- Bile: 30%
- T1/2: 6-9 hours 24 hours
- (intracellular t1/2 much longer, so can dose less frequently)
- SE:
- HEENT: stomatitis, (+/- pain)
- Pulm: hypersensitivity lung, fibrosis, pneumonitis
- GI: Diarrhea, N/V, hepatotoxicity (LE), cirrhosis
- Heme: thromobocytopeia
- Teratogenic: CI in pregs
- MTX is folic acid antag: can induce folic acid deficiency…
- Supplement (controversial):Folic acid 5mg daily OR Leucovorin once weekly (24 hours after MTX)
-
Hydroxychloroquine
- MoA:
- - Amtimalarial
- - MOA unknown
- - No effect on radiographic progression
- PK:
- A: “good and rapid”
- D: “wide” PB 50%, extensively tissue-bound in melanin-containing tissues (retinas)
- M: deaminated in liver
- E: t1/2 up to 45 days (long)
- SE:
- CNS: dizz, H/A, insomnia, dreams
- HEENT: decrease accommodation, bullseye retna,benign corneal deposits, burred vision, pre-retinopathy (Get ophthalmologist exam /yr)
- GI: N/V, D (decreased with food)
- Heme: hemolysis in G6PD def
- DERM: rash, alopecia, skin pigmentation
- May be used in pregnancy (if not already get complete absence of symptoms in pregnancy)
-
Sulfasalazine
- MoA:
- - MOA unknown
- - Sulfapyridine = antirheumatic props
- - decrease IgA and IgM rheumatoid factor prod.
- - Inhibit in vitro B cellproliferation
- - Decrease radiographic progression
- - Reduce sn/sx of RA
- PK: Prodrug cleaved by bacteria in colon to sulfapyridine & 5-ASA
- SE:
- HEENT: stomatitis
- GI: N/V/D, anorexia, increase LE
- Heme: leucopenia
- Oligospermia
- Derm: alopecia, rash, urticaria, serum sickness-like reactions, skin/urine turn yellow-orange
- Hypersensitivity to sulfa
- Ok for pregnancy
-
Gold
- MoA:
- - MOA: don’t have to know…reduce phagocytosis by macs, reduce proliferative response of lymphocytes, reduce IgA IgM RF production..etc
- - Actually unknown.
- - Given IM
- - Slow onset of action
- PK:
- Give10mg IM x1, then 25mg IM in 2nd week, then 50mg IM weekly -> response/1g
- If response, decrease to 50mg q2wks x 3mos, then q3wks x 3mos, then maintenance monthly dose (indefinitely).
- Tx failure: no response after total 1g administered.
- Onset: 4-6 mo or after 1g
- SE: Often lead to D/C
- HEENT: stomatitis
- GI: mucositis
- GU: proteinuria -> gold-ind’d membranous glomerulonephropathy -> nephritic syndrome; microscopic hematuria
- HEME: immune thrombocytopenia, granulocytopenia, aplastic anemia
- DERM: rash (pruritic erythematous -> severe exfoliative dermatitis); chrysiasis
- Inj rxns: nitritoid reaction (flush, dizz, faint)
- Monitoring:
- If mild mucocutaneous eruption, d/c tx.
- If eruption better, restart at 10-15mg/wk, increase to 50mg/wk.
- Chrysiasis- skin bluish gray forever.
- Not safe in pregs
-
Leflunomide
- MoA:
- - Indirectly inhibits protein synthesis
- - Competitive inhibitor of pyrimidine synth (enzyme DHODH) lymphocyte prolif + modulation of inflammation
- - Arrests activated lymphocytes in G1
- - Slows radiographic progression of joint damage
- - Prevents new joint erosions in 80% of patients over 2 year period
- - Similar efficacy to MTX
- PK:
- D:extensive PB
- E: urine, bile, t1/2 14-16 d
- Onset of action: 4-8 weeks
- SE:
- GI: reversible increase LE >3x ULN (esp w/ MTX)
- Diarrhea, GI upset
- DERM: alopecia
- Teratogenic - Adequate birth control (x2)
- If want to get pregs:
- - cholestyramine 8gtid x11d
- - 2x leflunomide levels drawn 14 days apart
- - Sr[] <0.02mg/L prior to conception
-
Cyclosporine
- MoA:
- - Immunosuppressive agent, calcineurin antagonist
- - Inhibits T cell fxn by inhibiting transcription of IL-2 (big contributor to RA)
- SE: Infection, Renal insufficiency, Hirsuitism
-
Etanercept(Enebrel)
- Soluble TNFR (recomb fusion protein)
- -structure: human p75 extracellular TNF receptor + human IgGI
- -mimics p75, takes up TNF in circulatin and inactivates them
- -onset: 1-4 weeks (v fast)
- -25mg SC twice weekly
- PK:
- A: 58% abs SC
- D: 0.11 L/kg
- M: neg
- E: renal – negligible
- Cl 0.02ml/min/kg
- T1/2: 4 days (IV 70 hrs, SC 92 hrs)
- Target: TNF/Lymphotoxin-alpha (both cytokines)
- SE:
- CNS: demyelinating syndromes (Do not give for pts with MS)
- Infections: increase Upper RTI, serious/opportunistic infections i.e. TB
- Heme: pancytopenia, neutropenia, blood dyscrasias
- Others: injection site rxns 37% (mild)
- 1% pts develop anti-etanercept Ab but non-neutralizing.
- Can activate latent TB…just treat concomitantly with INH?
-
Infliximab(Remicade)
- TNF MAb (chimeric): high affinity/spec.
- -stucture: mouse TNF binding site + human IgGI
- -binds TNF from macs in joints and circ, +inactivates them(px int’n with receptors on surface of inflamm cells)
- -onset: days to weeks
- -3-10mg/kg IV w/ MTX q4-8wks T1/2: 8-10 days
- Target: TNF
- SE:
- Infusion related:
- - “cytokine release syndrome” (fever, chills,h/a)…usually with first infusion and decreases w/ time
- Anti-infliximab Ab (10-30%) (MUST be used with MTX (blocks Ab that sucks up infliximab)
- Anti-DS DNA Ab
- Systemic lupus erythematosus (SLE)
- Sepsis and disseminated TB and other opportunistic infections
- Slow infusion rate.
-
Adalimumab (Humira)
- TNF MAb (recombinant)
- -structure: human TNF binding site + human IgGI
- 40mg SC qoweek T1/2: 10-20 days
- Target: TNF
-
Anakinra
- IL-1 blocker : human recombinant
- - IL-1 is immune and pro-inflammatory cytokine, autoinduction regulates own expression; mediates disease activity and progression of joint destruction, correlates with plasma/synovial fluid levels of IL-1.
- - IL-1ra is endogenous R antag.
- - Blocks IL-1 from binding to IL-1R by binding with same affinity.
- - Onset: 2-4 weeks Rapid onset of action…but not work well.
- SE:
- Injection site reactions (66%): mild erythema, itching, discomfort that reslves over 1-2 mo
- Infection: increased risk of serious ifxn (shutting down immune system...DO NOT use 2 biologics at same time. Combo increase risk of death from infection)
- Heme: neutropenia.
- Comboanakinra/etanercept: 3% severe neutr
- Neutralizing Abs rare: do not appear to correlate with clinical response or adverse events.
-
Abatacept
- - Selective T-cell co-stimulation modulator; recombinant human fusion protein:
- - EC human CTLA4 (cytotoxic T-lymphocyte-associated antigen-4) + Fc domain of human IgG1.
- - Normally, T-cell activation needs binding of CD28 and TCR to an APC; but CTLA-4 can displac binding of CD28 to CD80/86, therefore Tcell activation inhibition.
- - Abatacept acts like the CLTA4.
- - Onset: within 2-12 weeks. T1/2: 14.7 days
- Admin: silicone-free syr; IV 30min infusion once, then at week 2, 4, and every 4 weeks thereafter.
- Blocks not just TNF-alpha (macs), aso blocks IL-6 and MMPs from fibroblasts, and autoantibodies (RF) from b-cells…but response rate === other biologics (50-60%)
-
Rituximab
- - B-cell depletion
- - B-cells important in RA, and CD20 Ag is expressed on B-cells -> target!
- - Synthetic CD20 monoclonal Ab, selectively depletes CD20+ B cells
- - Chimeric murine/human MAb: mouse variable region (CD20 binding site) + human IgG1 constant region.
- - Onset: 2 months
- - Target: binds to CD20 antigen T1/2: 19.7 days
- Admin: 1000mg IV days 1-15 (50mg/h up to 400mg/h)
- Can go without dosng for up to 1.5 years! (mostppl need reinfuson after 6mo -1yr)
- Other drugs: risk of lymphoma…but rituximab can be used to treat lymphoma!
- *Depletes B cells w/o compromising immune
- Lethal brain condition…not much experience. Black box warning.
- Binds CD20 on pre to mature B cells (hematopoietic stem cells, pro-B cells, plasma cells, and other normal tissuesdo not have CD20 antigen)
-
Tocilizumab
- - Anti-IL-6 receptor antibody
- - IL-6 activates T-cells, B cells, induction of RF, differentiation of monocytes to macs, activation of osteoclasts…etc
- - 95% human, 5% mice, monoclonal recombinant humanized anti-IL-6 receptor Ab (murine binding site for IL-6 , human IgG1)
- - Binds directly to IL-6 receptor and prevents Il-6 from binding/activating
- - Onset: assessed at 12 weeks T1/2: 10 days
- Admin: 4-8mg/kg IV q4 wks
-
Tofacitinib
- - NOT a biological: just small molec
- - Designed based on congenital JAC3 deficiency -> immunodef. By blocking JAK, block inflamm cascade (many in pathogenesis of RA: IL-6,7.10…)
- - Efficacy===biologics
- - Orally active immunosuppressant
- - Inhibits janus activated kinase 3 (JAK3) Once daily dosing 20mg effective for tx RA. Anemia, diarrhea, increase nasopharyngitis infxns
- Interacts with fluconazole (increaseAUC and Cmax of tofacitinib)
- Safe for combo w/ MTX
|
|
Get the free mobile app
Take the Quiz
Learn more
Learn more