430 Immunosuppressive Agents Flashcards by Hope Manning

Rh(D) antibodies (RhoGAM)

Administered to the Rh negative mother within 72 hours after birth (neutralize the Rh positive antigens at birth)

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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

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Cyclosporine ADME (bioavailability, peak, half-life, metabolism, excretion)

Bioavailability 20-50% 
Peak < 3-4hrs 
Half-life 6hrs
Metabolized by liver 
Excreted in bile

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Cyclosporine DDI

Induce cyt P450–accelerate clearance

Inhibit cyt P450–reduce clearance

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Cyclosporine toxicity

renal and nephrotoxicity

HTN, neurological, elevated hepatic transaminase, hirsutism and gingival hyperplasia

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Cyclosporine indications

tissue transplantation
GVHD
Autoimmune diseases

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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

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Tacrolimus ADME (bioavailability, peak, metabolism, half-life, excretion)

Bioavailability 25% 
Peak 1-4 hrs 
Metabolized in liver 
Half-life 10hrs 
Excreted in urine

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Tacrolimus side effects

HA, tremors, insomnia, nausea, GI discomfort, lymphoproliferative disorders

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Tacrolimus indications

Tissue transplantation

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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

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Rapamyin ADME (metabolism)

Metabolized in liver

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Rapamycin DDI

Induce cyt P450–accelerate clearance

Inhibit cyt P450–reduce clearance

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Rapamycin side effects

impaired wound healing (b/c of apoptosis), allergic reaction, increase risk of infection

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Rapamycin Indications

Prevention of tissue rejection
Cancer
Good in combination with cyclosporine

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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

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Everolimus indications

Prevention of graft rejection
Cardiac allograft vasculopathy
Post-transplant lymphoproliferative disorders

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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)

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Fingolimod indications

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Multiple sclerosis (delay progression) 
Potential for heart failure and arrhythmia

Fingolimod side effects

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Fatal infection
Bradycardia
Hemorrhage

Belatacept MOA

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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

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Prophylaxis for rejection of kidney transplant

ONLY given to Epstein-Barr seropositive patients

Belatacept side effects

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Increase risk of post-transplant lymphoproliferative disorder (PTLD)
Increase risk of infection
Development of malignancies

Abatacept MOA

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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)

430 Immunosuppressive Agents Flashcards

(45 cards)