Immunopharmacology Flashcards
Glucocorticoids
Surface receptor mediated, very quick response. Cause lysis and redistribution of lymphocytes and prevent lymphocytes from leaving the vasculature.
Genomic response: increase apoptosis of lymphocytes and inhibit synthesis of pro-inflammatory cytokines.
Prevent and treat transplant rejection, RA, IBS, and hypersensitivity
Adverse Effects: Adrenal suppression and increase risk of infection, hyperglycemia, slow wound healing, cataracts, ulcers, increased risk of osteoporosis.
Calcineurin inhibitors
binding reactions block calcineurin’ s phosphatase activity, required for movement of a component of NFAT into the nucleus, blocking the production of IL-2 (preventing activation of T-cells)
Cyclosporine
Calcineurin inhibitors - binds to cyclophilin (an immunophilin)
Highly lipophilic, oral administration is optimized using oil-based solubilization methods
Complex pharmacokinetics require modeling of individual patient blood curves.
Toxicity: Renal dysfunction and hypertension, hyperglycemia.
Sirolimus- cyclosporine combination increases nephrotoxicity, hyperlipidemia, and myelosuppression (super additive effects - can prevent by separating dosing)
Indicted for inflammation associated ocular dryness
Tacrolimus
Calcineurin inhibitors - binds to FKBP-12
More efficacious than cyclosporine and has easier monitoring – patients able to dose themselves
Toxicity: Nephrotoxicity, neurotoxicity, hyperglycemia, risk of secondary tumors and opportunistic infections.
Grapefruit Interaction (makes drug less effective)
P-glycoprotein
Methotrexate (Rheumatrex Dose Pack)
Anti-Proliferative/Anti-Metabolic
Inhibitor of dihydrofolate reductase
Inhibition leads to depletion of reduced folates and inhibits purine synthesis
Subtle way of attacking DNA, disrupts cell division
Greatest effect on B cells.
Used for autoimmune and organ transplants.
Cyclophosphamide
Anti-Proliferative/Anti-Metabolic
Converted to alkylating agent that irreversibly complexes with DNA – preventing DNA replication
Toxic to most proliferating cells - greatest effect on B cells.
Used for autoimmune diseases and organ transplants
Adverse effects: Bone marrow suppression, increase risk of infection, bladder cystitis.
Mycophenolate Mofetil
Anti-Proliferative/Anti-Metabolic - NOT an anti-inflammatory.
Converted to mycophenlic acid, inhibits purine synthesis. Suppresses both B and T cell activation. Intravenous and oral administration. Used for organ transplants
Adverse effects: bone marrow suppression and increase risk of infection
Azathioprine
Anti-Proliferative/Anti-Metabolic
Converted first to mercaptopurine (anticancer drug) and then to false nucleotides that inhibit purine pathways
Inhibits T cell function more than B cell function
Powerful anti-inflammatory
Used for autoimmune disorders and organ transplants.
Adverse effects: bone marrow suppression and increased risk of infections
Allopurinol inhibits biotransformation of azathioprine and mercaptopurine (inhibits inactivation) increasing toxicity
Sirolimus & Everolimus
Anti-Proliferative/Anti-Metabolic
Binds FKBP-12 that complexes with mammalian target of Rapamycin (mTOR) to block activation of T-Cells in cell cycle
Inhibits the response to interleukin-2 but does not alter production (as compared to cyclosporin and tacroliuc)
Very selective on T-cells
used for organ transplants
Adverse effects: Renal failure and hypertension, hyperglycemia, and hyperlipidemia
Etanercept (Enbrel)
Biologics
Binds the inflammatory TNF-α (significant inflammatory mediator) and depletes it. Blocks the inflammatory response through decreased interleukin release
Used for RA
Increase risk of infections and hypersensitivity
Infliximab
Biologics
Binds Tumor Necrosis Factor-α
Suppresses cytokine synthesis and release
Used for Crohn’s disease and RA
Adverse reactions: fever, chills, aches, flu-like, increase risk of infections (TB), hypersensitivity, congestive heart failure exacerbation. Increase risk of cancer - especially in adolescents.
Antithymocyte Globulin (ATG, Thymoglobulin)
Biologics - used if already experiencing rejection. Cytotoxic antibodies bind to surface T-cell antigens, and try to clear out T cells.
Used for acute transplant rejection, not used to prevent rejection.
Adverse: Hypersensitivity, fever and chills and hypotension.
Muromonab-CD3
Biologics - obtained from mouse
Anti-CD3 monoclonal antibodies, on the surface of T-lymphocytes. Blocks out T cells and recognition site for signaling and proliferation.
Used in acute organ transplant rejection - stop a rejection from occurring.
Adverse reactions: hypersensitivity, cytokine release syndrome (storm). (minimized by pretreatment with corticosteroids and antihistamines)
Daclizumab & Basiliximab
Biologics
Generally low toxicity however - hypersensitivity, increased risk of infections, heart failure, and cancer (esp. adolescents).
Thalidomide
Immunoenhancer
Unknown mechanism of action
suppresses TNF-a but increases in HIV patients, anti-angiogenic actions.
Used for leprosy, cancer, immune disorders and wasting syndrome in AIDS
Pregnancy category X
