430 Immunosuppressive Agents Flashcards
Rh(D) antibodies (RhoGAM)
Administered to the Rh negative mother within 72 hours after birth (neutralize the Rh positive antigens at birth)
Cyclosporine MOA
Enters T cell, binds to cyclophilin receptor creating a cyclophilin-cyclosporine complex
Inhibits calcineurin
Inhibits synthesis and secretion of IL-2
Inhibits expression of IL-2 receptors
Cyclosporine ADME (bioavailability, peak, half-life, metabolism, excretion)
Bioavailability 20-50% Peak < 3-4hrs Half-life 6hrs Metabolized by liver Excreted in bile
Cyclosporine DDI
Induce cyt P450–accelerate clearance
Inhibit cyt P450–reduce clearance
Cyclosporine toxicity
renal and nephrotoxicity
HTN, neurological, elevated hepatic transaminase, hirsutism and gingival hyperplasia
Cyclosporine indications
tissue transplantation
GVHD
Autoimmune diseases
Tacrolimus MOA
Enters T cell, binds to immunophilin FKBP, creating a Tacrolimus-immunophilin complex
Inhibits calcineurin
Inhibits IL-2 synthesis and secretion
Inhibits expression of IL-2 receptor
Tacrolimus ADME (bioavailability, peak, metabolism, half-life, excretion)
Bioavailability 25% Peak 1-4 hrs Metabolized in liver Half-life 10hrs Excreted in urine
Tacrolimus side effects
HA, tremors, insomnia, nausea, GI discomfort, lymphoproliferative disorders
Tacrolimus indications
Tissue transplantation
Rapamycin MOA
Enter T cell and bind to immunophilin, creating rapamycin-immunophilin complex
Inhibits mTOR (which inhibits IL-2 signaling)
Inhibits cyclin E (which inhibits cell cycle from G1 to S phase)
-blocks T cell proliferation
-apoptosis
Rapamyin ADME (metabolism)
Metabolized in liver
Rapamycin DDI
Induce cyt P450–accelerate clearance
Inhibit cyt P450–reduce clearance
Rapamycin side effects
impaired wound healing (b/c of apoptosis), allergic reaction, increase risk of infection
Rapamycin Indications
Prevention of tissue rejection
Cancer
Good in combination with cyclosporine
Everolimus MOA
Enter T cell and bind to immunophilin, creating everolimus-immunophilin complex
Inhibits mTOR (which inhibits IL-2 signaling)
Inhibits cyclin E (which inhibits cell cycle from G1 to S phase)
-blocks T cell proliferation
-apoptosis
Everolimus indications
Prevention of graft rejection
Cardiac allograft vasculopathy
Post-transplant lymphoproliferative disorders
Fingolimod MOA
Binds to G-protein linked S1P1 receptor present of lymphocytes and thymocytes
Internalization of the receptor (unable to egress from lymphoid organs)
Second MOA—causes lymphocytes to move from circulation into secondary lymphoid tissues (decrease peripheral blood lymphocyte count)
Fingolimod indications
Multiple sclerosis (delay progression) Potential for heart failure and arrhythmia
Fingolimod side effects
Fatal infection
Bradycardia
Hemorrhage
Belatacept MOA
Fused Fc of IgG1 with EXTRA cellular domain of CTLA-4 (CD152) binds to CD80/86 to decrease activation of helper T cells
Belatacept indications
Prophylaxis for rejection of kidney transplant
ONLY given to Epstein-Barr seropositive patients
Belatacept side effects
Increase risk of post-transplant lymphoproliferative disorder (PTLD)
Increase risk of infection
Development of malignancies
Abatacept MOA
Differs from Belatacept by TWO amino acids
Fused Fc of IgG1 to CTLA-1 (CD152) binds to CD80/86 and decreases T cell activation
Abatacept Indications
Treat RA in those who don’t respond to other treatments (delays progression of structural damage)
NOT used in combination with Kineret and TNFalpha drugs
Abatacept side effects
Flu-like symptoms: fatigue, sore throat, drug cough, trouble breathing, wheezing, fever, chills, night sweats
Adrenocortical steroids MOA
Inhibit T cell proliferation
Inhibit expression of encoding cytokines (IL-2, IL-1, IL-6, IFNalpha, TNFalpha)
Anti-adhesion effects
Adrenocortical steroids Indications
Preventing transplant rejection
Autoimmune disorders
Minimize allergic reactions with monoclonal antibodies
LARGE doses—reversal of acute graft rejection
LOW doses—prevent GVHD
Cytotoxic drugs MOA
Kill both B and T cells
Prevent the expansion of both B and T cells
Azathioprine (cytotoxic drug) indications
Prevent transplant rejection (combination with other immunosuppressive agents or prednisone)
Reserved for patients not responding to other therapies
Azathioprine (cytotoxic agent) side effects
Leukopenia Thrombocytopenia GI toxicity Hepatotoxicity Carcinogenicity
Mycophenolate Mofetil MOA
Selective for B and T lymphocytes because of its reliance on the de novo pathway (NOT salvage pathway)
Suppresses lymphocyte proliferation and antibody formation by B cells
Inhibit recruitment of leukocyte glycoproteins to inflammatory sites
Mycophenolate Mofetil ADME (bioavailability, metabolism, elimination)
Bioavailability 94%
Metabolized by glycuronyl transferase to active metabolite
Eliminated in urine
Mycophenolate Mofetil DDI
Antacids containing Mg and Al leads to decreased absorption
Mycophenolate Mofetil Indications
After renal, heart, liver transplantation
Combination with cyclosporine and corticosteroids
Cyclophosphamide MOA
Alkylates DNA in proliferating cells (B and T cells)
Cyclophosphamide indications
Large doses: immunosuppressive agent in bone marrow transplants
Small doses: treat variety of autoimmune disorders
Methotrexate indications
treatment of RA
Methotrexate side effects
Chronic use of low dose can produce liver toxicity
Muromonoab-CD3 (OKT3) MOA
Polyclonal antibody directed against T cells and specific for 20,000-dalton glycoprotein in CD3 complex
Antibody itself is directed against polypeptide present in CD3 complex
Muromonoab-CD3 (OKT3) indications
Adjuvant for acute rejection in allograft (no prevention of rejection except in bone marrow transplantation to prevent GVHD)
Muromonoab-CD3 (OKT3) side effects
Flu-like symptoms (chills, fever)
Dyspnea, chest pain, wheezing, GI effects
Pulmonary edema (fatal)
Reversible CNS syndrome
Methoxsalen indications
ONLY used for treatment of T cell lymphoma resistant to standard therapy
Methoxsalen MOA
2 hours after patient is given methoxsalen blood is removed and exposed to ultraviolet light—radiated cells are returned to patient and process repeated again in 24hrs
Methoxsalen intercalates into DNA and modifies DNA structure inhibiting T cell function (killing T cells and stop immune reaction)
Immunostimulants (boost immune response)
BCG (vaccine for TB, protects against leprosy)
Levamisole
Isoprinosine
Cytokines (IFN alpha, IL-2)
