Immunosuppressants for Immuno exam Flashcards
What are the three major indications for immunosuppressants?
- Organ Transplant Rejection
- Chronic inflammatory diseases
- Autoimmune diseases
What are the major adverse effects of immunosuppressants?
Increased risk for infections and malignancies
What is the MOA of prednisone?
- Antinflammatory effects at lower doses: decrease synthesis of inflammatory mediators and decrease expression of adhesion molecules for extravasation
- Anti-inflammatory +immunosuppress effects at higher doses: increase expression of proteins that promote apoptosis
What are the major indications of prednisone?
- Inflammatory disorders like osteoarthritis
- Systemic inflammatory autoimmune diseases like RA, SLE, IBD
- Organ transplant rejection
- GVHD prophylaxis following bone marrow transplant
- T cell mediated hypersensitivities like poison oak and chronic asthma
What are side effects of prednisone?
Cushings syndrome and caution for adrenal suppression
Cyclosporine (TCR signaling inhibitors) MOA
Inhibit T cell intracellular signal 1 that is initiated by CD3 after TCR and co-receptor bind to p-MHC (signal 1) –> inhibits calcineurin which decreases T cell activation
Cyclosporine indications
- Systemic autoimmune disease like RA
- Organ transplant rejection prophylaxis
- GVHD prophylaxis following bone marrow transplant
Cyclosporine specific AEs
- Nephrotoxicity
- Hypertension
- Neurotoxicity
- Electrolyte abnormalities
- Gingival hyperplasia
- Hirsutism
Belatacept MOA
CTLA-4 binds to B7 and prevents T-cell activation via CD28 via signal 2
Belatacept indication
Organ transplant rejection prophylaxis
Belatacept AEs
Typical class effect (increased risk of infections and malignancies) and could cause PTLD or post-transplant lymphoproliferative disorder
Natalizumab MOA
Blocks VLA-4 and prevents extravasation of effector T cells into inflamed tissue (brain in MS, joints in RA, colon in IBD)
Natalizumab indication
Autoimmune diseases like MS
Natalizumab adverse effects
Typical class effect (increased risk of infections and malignancies) and increased risk of PML or progressive multifocal leukoencephalopathy
Rituximab (Anti-CD20 mab) MOA
Binds CD20 on B cells then initiates complement or ADCC to kill B cells which decreases circulating B cells & decreases absorption that mediates part of the inflammatory process of disease –> also kills tumor B-cells as well as normal B cells
Indications for rituximab
- Relapsing/remitting MS
- Antibody-mediated systemic autoimmune complex diseases like RA and SLE
- Non-Hodgkins B cell lymphoma
Rituximab AEs
- Hepatitis B reactivation
- Increased risk of progressive multifocal encephalopathy (PME)
Infliximab (Anti-TNF mab) MOA
Prevents TNF from activating its R and decreases inflammatory effects and innate response
Infliximab Indications
- Some systemic autoimmune diseases like RA and IBD
- Psoriatic arthritis
Infliximab AE
Increased risk of TB as well as other infections
T/F: Adalimumab is a mouse antibody
False, it is a TNF humanized antibody because it has the suffix mumab
Cetuximab (anti-EGFR mAb) MOA
IgG binding to cell EGFR causes initiation of ADCC to allow NK cells to kill tumor cells –> also blocks EGFR signaling which impairs tumor growth and survival
Cetuximab indications
Used in tumors that overexpress EGFR as a cancer driver mutation
Cetuximab side effects
Rash and diarrhea
Anakinra MOA
Prevents IL-1 receptor activation and decreases it
Anakinra indication
Hereditary fever syndromes like FMF
Anakinra AEs
Class effects only (increase risk of infections and malignancies)
Tocilizumab MOA
Binds to IL-6 receptor and decreases it which leads to lower inflammation
Tocilizumab indications
RA
Tocilizumab AEs
Class effects (increased risk of infections and malignancy)
Trastuzumab MOA
mAB to HER-2 and blocks HER-2 signaling (leads to impaired tumor cell growth/survival) and has IgG mAB bind to HER-2 (initiates ADCC to allow NK cells to kill tumor cells)
Trastuzumab indications
Tumors overexpressing HER-2
Anti-CTLA-4 mAB MOA
Prevents inhibition of clonal expansion of T cells and allows a stronger T cell response against cancer and other tissues
Anti-CTLA-4 indications
Melanoma
Anti-PD1 mAB MOA
Prevents the inhibitory signal and allows CD8 T cells to kill the cancer cells
Anti-PD1 indications
Many solid and hematologic cancers like melanoma, colon cancer, lung cancer, lymphoma
Anti-CTLA and anti-PD1 adverse effect
Excessive T cell mediated inflammation in various organs
Albuterol (B2 agonist) MOA
Stimulates B cell receptors on airway SM and causes bronchodilation but less effective with chronic inflammation
Albuterol indications
Acute allergic asthma
Albuterol AEs
- Tremor
- CNS effects like anxiety
- Increased HR
Epinephrine (mixed a/B agonist) MOA
- Stimulates B2 receptors on airway smooth muscle which causes bronchodilation
- Stimulates a1 receptors on vascular SM which increases SVR and blood pressure
- stimulates a1 receptors on ECs which reclose tight junctions and decrease edema
Epinephrine indications
Anaphylaxis
Epinephrine AEs
Increased HR and cardiac arrhythmias
Omalizumab (anti-IgE mAB) MOA
Binds Fc of soluble IgE and decreases binding to FCE receptors on mast cell (early response) and eosinophils (delayed response)
Omalizumab indications
- Moderate to severe allergic asthma
- Chronic idiopathic urticaria
Chlorpheniramine (1st gen) and fexofenadine (2nd gen) ( both are H1-R antagonists) MOA
Blocks H1-R and decreases histamine mediated symptoms caused by HM release from mast cells
H1-R antagonist indications
Allergic rhinitis and urticaria (poison ivy or oak)
Mepolizumab (anti-IL-5 mAB) MOA
Binds IL-5 and decreases activation of its receptor which leads to decreased activation/recruitment of eosinophils
Mepolizumab indications
Severe asthma and chronic allergic dermatitis
Montelukast (LT R antagonist) MOA
Blocks CysLT receptors and decreases LT symptoms
Montelukast indications
Allergic rhinitis and chronic asthma
