Immunology - Immunosuppressants Flashcards
Which immunosuppressant binds to cyclophilins?
Cyclosporine
What is the mechanism of action of cyclosporine?
Cyclosporine-cyclophilin blocks the differentiation of T cells by inhibiting calcineurin and preventing production of interleukin-2 and its receptor
What are the clinical uses of cyclosporine?
Cyclosporine is used to treat some autoimmune disorders
What are the adverse effects of cyclosporine use, and how is it prevented?
Nephrotoxicity, which can be prevented with mannitol diuresis
Which immunosuppressant is similar to cyclosporine but functions by binding to FK-binding protein instead of cyclophilins?
Tacrolimus (FK-506)
Tacrolimus works by binding to the FK-binding protein, thereby inhibiting the secretion of _____-_____ and other cytokines.
Interleukin-2
Tacrolimus is used as an immunosuppressant for which patient population?
Organ transplant recipients
What toxicities are associated with tacrolimus use?
Nephrotoxicity, peripheral neuropathy, hypertension, pleural effusions, and hyperglycemia
Which two immunosuppressant drugs function as calcineurin inhibitors?
Cyclosporine and tacrolimus
Which drug is an antimetabolite derivative of 6-mercaptopurine that interferes with the metabolism and synthesis of nucleic acids?
Azathioprine
Why does azathioprine act as an immunosuppressant?
Azathioprine is toxic against proliferating lymphocytes
What are the clinical indications for use of azathioprine?
As an immunosuppressant during kidney transplantation and for autoimmune disorders
What is the major adverse effect of azathioprine use?
Bone marrow suppression
How does allopurinol exacerbate the toxic effects of azathioprine?
Mercaptopurine (the active metabolite of azathioprine) is metabolized by xanthine oxidase (which is inhibited by allopurinol)
Muromonab-CD3 (OKT3) is a monoclonal antibody that binds to which protein on the surface of T cells?
CD3
How does muromonab-CD3 (OKT3) work?
By blocking binding to the CD3 protein on the T-cell surface, which inhibits signal transduction and cellular function
In what clinical scenario is muromonab-CD3 (OKT3) used?
For immunosuppression after kidney transplants
What two types of reactions are associated with muromonab-CD3 (OKT3) toxicity?
Cytokine release syndrome and hypersensitivity reaction
What is the mechanism of action of sirolimus, and what effect does this have on immunity?
Sirolimus binds mammalian target of rapamycin and inhibits T-cell proliferation in response to interleukin-2
What two other drugs are commonly used in conjunction with sirolimus after kidney transplantation for immunosuppression?
Cyclosporine and corticosteroids
What three toxicities are associated with the use of sirolimus?
Hyperlipidemia, thrombocytopenia, leukopenia
What is the mechanism of action of mycophenolate mofetil, and what effect does it have?
Mycophenelate mofetil inhibits de novo synthesis of guanine and blocks lymphocyte production
What is the mechanism of action of daclizumab?
Daclizumab is a monoclonal antibody that blocks interleukin-2 receptors on T cells
What is aldesleukin?
Recombinant interleukin-2
