Immunopharmacology Flashcards
What are the clinical uses and limitations to immunosuppression therapy?
Clinical: Autoimmune disorders, Organ transplantation
Limitations: Increased infection risk, Increased risk for cancer (lymphomas), drug toxicity
What is the goal of induction therapy?
Provide strong immunosuppressive at the time of surgery to reduce the incidence of acute rejection
What is the goal of maintenance therapy?
Preserve the allograft for many years with a multidrug approach for immunosuppression without drug toxicity and infection risk
What is the goal of rescue therapy?
Rescue the allograft from an immune attack, treating transplant rejection
What are the two calcineurin inhibitors?
Cyclosporine and Tacrolimus
What is the MoA for cyclosporine and tacrolimus?
Inhibit calcineurin in T cells, preventing the regulation of NFAT, resulting in decreases in IL-2 synthesis and inhibition of T cell activation
Also increase TGF-B
What are the therapeutic uses and adverse effects of cyclosporine and tacrolimus?
Therapy: Prevent transplant rejection, autoimmune disorders
Adverse effects: Nephrotoxicity, hypertension, neurotoxicity, hepatotoxicity, post-transplant diabetes
What is the MoA, Therapeutic uses, and AE’s of glucocorticoids Prednisone and prednisolone?
MoA - Induce nonspecific immunosuppression by inhibiting T cell expanison, decreasing pro-inflammatory cytokines IL-1 and IL-6
Therapy: Prevent and treat transplant rejection
AE’s: hyperglycemia, hypertension, weight gain, increased risk of infection, osteoporosis, psychosis
What are the mTOR inhibitors and their MoA?
Sirolimus and Everolimus
MoA - Inhibit mTOR kinase, which is a key enzyme in cell cycle progression at G1->S phase transition
Inhibits IL-6 stimulated T cell expansion
What are the therapeutic uses, AE’s, and beneficial effects of mTOR inhibitors?
TU: prophylaxis of organ transplant rejection, incorporated into stents to inhibit occlusion
AE’s: Hyperlipidemia, anemia, leukopenia, thrombocytopenia, delay in wound healing and graft function
Benefits: anticancer effects, non nephrotoxic
What is the MoA, therapeutic uses, and AE’s for azathioprine?
MoA - prodrug converted to 6-mercaptopurine, which are incorporated into DNA, inhibiting synthesis. Also inhibits de novo purine synthesis, which lymphocytes rely on
Therapy: adjunct for prevention of organ transplant rejection, RA
AE’s: bone marrow suppression, increased infection risk, hepatotoxicity, alopecia, GI toxicity
What is the drug interaction for azathioprine?
If allopuinol is given, reduce AZA dose
What is the MoA, therapeutic uses, and AE’s for Mycophenolate mofetil (MFF)?
MoA - prodrug converted to mycophenolic acid, reversible inhibitor of inosine monophosphate dehydrogenase, inhibiting de novo synthesis of guanine
Therapy: Used in combination with GCs and calcineurin inhibitors for prophylaxis of transplant rejection
AE’s: GI and hematologic, contraindicated in pregnancy
What is the MoA, therapeutic uses, and AE’s for Muromonab-CD3?
MoA - monoclonal antibody that depletes CD3 positive cells, internalization of TCR, blocks antige-mediated actrivation of T cells
Therapy: induction therapy, treat transplant rejection
AE’s: Cytokine release syndrome, pulmonary edema
What is the MoA, therapeutic uses, and AE’s for Antithymocyte globulin (ATG)?
MoA - Cytotoxic antibodies against numerous T-cell surface molecules
Therapy: Induction therapy, treatment of transplant rejeciton
AE’s: Fever, chills, hypotenstion, serum sickness, nephritis, anaphylaxis
What is the MoA, therapeutic uses, and AE’s for Anti-CD25 (anti-IL-2 receptor)?
Basilixmab, Daclizumab
MoA - block IL-2 mediated T-cell activation
Therapy: Induction therapy, prophylaxis of acute organ rejection. Daclizumab usef for relapsing MS
AE’s: Good safety profile
What is the MoA, therapeutic uses, and AE’s for Anti-CD52 (Alemtuzumab)?
MoA - binds CD52 on B and T cells, macrophages, NK cells and some granulocytes. Induces ADCC of cells and a profound leukopenia that may last for more than a year
Therapy: Chronic lymphocytic leukemia, MS, induction therapy, transplant rejection
AE’s: Profound leukopenia that may last for over a year. Neutropenia most common
What is the MoA, therapeutic uses, and AE’s for Anti-CD20 (Rituximab)?
MoA - deplete circulating mature B lymphocytes
Therapy - Chronic lymphoid leukemia, non-Hodgkin’s lymphoma and RA, induction therapy
AE’s: -
What is the MoA, therapeutic uses, and AE’s for Alefacept?
MoA - Blocks interaction between LFA-3 and CD2, inhibiting adhesion between APCs and T cells
Therapy: Psoriasis
What is the MoA, therapeutic uses, and AE’s for Anti-IL6 antibody (Tocilizumab)?
MoA - Inhibits binding of IL-6 to both soluble and membrane bound receptors
Therapy - juvenile RA, RA
AE - good safety profile
What are the Anti-TNF drugs?
Infliximab
Certolizumab pegol
Adalimumab
Etanercept
Golimumab
What is the MoA, therapeutic uses, and AE’s for Anti-TNF drugs?
MoA - binds to and neutralizes TNFa
Therapy - RA, Crohn disease, plaque psoriasis, psoriatic arthritis, ulcerative colitis
AE’s: Infucsion reaction with fever, urticaria, hypotension, dyspnea
What are abatacept and belatacept?
CTLA4-IgG1 fusion proteins
MoA - Block the costimulatory pathway in T cells
Therapy - prophylaxis of organ rejection
AE’s - increased risk of post-transplant lymphoproliferative disorder involving the CNS, progressive multifocal leukoencephalopathy, CNS infections
What is Rho(D) immunoglobulin?
High titer IgG against Rho antigen on the surface of RBCs
Prevents hemolytic disease of the newborn
What is thalidomide?
Immunomodulatory activity
Used in erythema nodosum leprosum, and multiple myeloma
Contraindicated in pregnancy
What is Levamisole?
Inhibits T-suppressor cells
Used as immunostimulant in colon cancer
What is Bacillus Calmette-geurin?
Viable attenuated strain of Mycobacterium bovis
Stimulates NK and T cell activity
Used in bladder cancer treatment
Severe hypersensitivity can develop
What are the uses for interferons?
Chronic HCV and HBV infection, Kaposi sarcoma, MS
What is Aldesleukin?
IL-2
Used to treat metastatic melanoma and renal cell cancer
Toxicity - inflammation and vascular leak, hypotension
What are myeloid colony stimulating factors?
Used for neutropenia, BMT, HIV, aplastic anemia
