USMLE (Subject) / Pharmacology - Immunology (Lesson)

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  • Cetuximab Target: EGFR Clinical use: - Stage IV colorectal cancer- Head and neck cancer
  • Rituximab Target: CD20 Clinical use: - B-cell non-Hodgkin lymphoma- CLL- Rheumatoid arthritis- ITP- Multiple sclerosis
  • Trastuzumab Target: HER2/neu Clinical use: - Breast cancer- Gastric cancer
  • Bevacizumab Target: VEGF Clinical use: - Colorectal cacer- Renal cell carcinoma- Non-small cell lung cancerOcular:- Neovascular age-related macular degeneration- Proliferative diabetic retinopathy- Macular edema
  • Alemtuzumab Target: CD52 Clinical use: CLL, multiple sclerosis
  • Cyclosporine Calcineurin inhibitor, binds cyclophilin.Blocks T-cell activation by preventing IL-2 transcription. Use:- Psoriasis- Rheumatoid arthritis Toxicity:- Nephrotoxicity- Hypertension- Hyperlipidemia- Neurotoxicity- Gingival hyperplasia- Hirsutism
  • Tacrolimus (FK506) Calcineurin inhibitor (like cyclosporine), binds FK506 binding protein.Blocks T-cell activation by preventing IL-2 transcription.  Use: Transplant rejection prophylaxis Toxicity: Similar to cyclosporine (nephrotoxicity, hyperlipidemia, hypertension)- ↑ risk of diabetes and neurotoxicity- No gingival hyperplasia or hirsutism
  • Sirolimus (Rapamycin) mTOR inhibitor; binds FKBP.Blocks T-cell activation by preventing response to IL-2.Synergistic with cyclosporine. Use: - Kidney transplant rejection prophylaxis specifically- Drug-eluting stents Toxicity:- Pancytopenia ("pansirtopenia")- Insulin resistance- Hyperlipidemia- Not nephrotoxic
  • Azathioprine Antimetabolite of precursor of 6-mercaptopurine.Inhibits lymphocyte proliferation by blocking nucleotide synthesis. Use:- Rheumatoid arthritis- Crohn disease- Glomerulonephritis- Other autoimmune conditions Toxicity: - Pancytopenia- 6-MP degraded by xanthine oxidase → toxicity ↑ by allopurinol
  • TNF-α inhibitors Adalimumab, certolizumab, golimumab, infliximab Clinical use:- IBD- Rheumatoid arthritis- Ankylosing spondylitis- Psoriasis - Etanercept is a decoy TNF-α receptor and not a monoclonal antibody
  • Basiliximab Monocloncal antibody; blocks IL-2 receptor. Use: Kidney transplant rejection prophylaxis Adverse effects:- Edema- Hypertension- Tremor
  • Mycophenolate mofentil Reversibly inhibits IMP dehydrogenase, preventing purine synthesis of B and T cells. Use: - Lupus nephritis- Used in combination with cyclosporin or tacrolimus as transplant rejectionprophylaxis Adverse effects:- GI upset- Pancytopenia- Hypertension- Hyperglycemia, hypercholesterolemia- Elevated BUN- Peripheral edema- Less nephrotoxic and neurotoxic - Associated with invasive CMV infection
  • Aldesleukin Interleukin-2 Clinical use:- Renal cell carcinoma- Metastatic melanoma
  • Interferon-α Clinical use:- Chronic hepatitis C and B- Renal cell carcinoma
  • Interferon-β Clinical use:- Multiple sclerosis
  • Interferon-γ Clinical use:- Chronic granulomatous disease
  • Daclizumab Target: CD25 (part of IL-2 recptor) Clinical use:- Relapsing multiple sclerosis
  • Eculizumab Target: Complement protein C5 Clinical use:- Paroxysmal nocturnal hemoglobulinuria
  • Natalizumab α4-integrin Clinical use:- Multiple sclerosis- Crohn disease - α4-integrin: WBC adhesion- Risk of PML in patients with JC-virus
  • Ustekinumab Target: IL-12/IL-23 Clinical use:- Psoriasis- Psoriatic arthritis
  • Abciximab Target: Platelet glycoproteins IIb/IIIa Clinical use: Antiplatelet agent for prevention of ischemic complications in patients undergoing percutaneous coronary intervention
  • Denosumab Target: RANKL Clinical use:- Osteoporosis; inhibits osteoclast maturation (mimics osteoprotegerin)
  • Omalizumab Target: IgE Clinical use: Refractory allergic asthma; prevents IgE binding to FcεR
  • Palivizumab Target: RSV F protein Clinical use: RSV prophylaxis for high-risk infants
  • Glucocorticoids Inhibit NF-κB. Suppress both B- and T-cell function by ↓ transcription of many cytokines.Induce T cell apoptosis. Use:- Many autoimmune and inflammatory disorders- Adrenal insufficiency- Asthma- CLL, non-Hodgkin lymphoma Toxicity:- Cushing syndrome- Osteoporosis- Hyperglycemia- Diabetes- Amenorrhea- Adrenocortical atrophy- Peptic ulcers- Psychosis- Cataracts- Avascular necrosis (femoral head) - Demargination of WBCs causes artificial leukocytosis. - Adrenal insufficiency may develop if drug is stopped abruptly after chronic use.
  • Colony stimulating factors Filgrastim (G-CSF)Sargramostim (GM-CSF) Clinical uses:- Leukopenia- Recovery of granulocyte and monocyte counts
  • Thrombopoietin Romiplostim (TPO analog)Eltrombopag (TPO receptor agonist) Clinical use:- Autoimmune thrombocytopenia