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
