Immunopharm Flashcards
1
Q
Immunosuppressive Drugs
A
- Glucocorticoids
- Calcineurin Inhibitors
- mTOR Inhibitors
- Inhibitors of Angiogenesis
- Cytotoxic Agents
- Immunosuppressive Antibodies
2
Q
CALCINEURIN INHIBITORS
A
- includes Cyclosporine & Tacrolimus
MOA
- Calcineurin is a phosphatase necessary for activation of a T- cell-specific transcription factor: NFAT.
- NFAT is required for the induction of cytokine genes.
- Cyclosporine forms a complex with cyclophilin, an immunophilin.
- This complex inhibits calcineurin.
- Cyclosporine forms a complex with cyclophilin, an immunophilin -> inhibits calcineurin.
Uses: organ transplantation, uveitis, rheumatoid arthritis, and psoriasis.
3
Q
CYCLOSPORINE: ADVERSE EFFECTS
A
- Main adverse reactions: Nephrotoxicity,tremor, hypertension, hyperglycemia, hyperlipidemia, osteoporosis, hirsutism, gum hyperplasia.
- Nephrotoxicity is limiting and occurs in the majority of patients treated. It is the major indication for cessation or modification of therapy.
- Very little bone marrow toxicity.
Drug interactions: primarily metabolized by CYP3A4: involved in many drug interactions.
4
Q
TACROLIMUS
A
- Tacrolimus binds to FK-binding protein (FKBP).
- FKBP is an immunophilin.
- The tacrolimus-FKBP complex inhibits calcineurin.
Uses
- organ and stem cell transplantation.
- atopic dermatitis and psoriasis.
5
Q
Sirolimus
A
- MAMMALIAN TARGET OF RAPAMYCIN (mTOR) INHIBITORS
- Structurally similar to tacrolimus.
- Sirolimus binds to FKBP .
- But the sirolimus-FKBP complex does not inhibit calcineurin.
- Instead, it inhibits the serine-threonine kinase mTOR.
- Blockade of mTOR blocks IL-2-driven T-cell proliferation.
6
Q
Thalidomide
A
- INHIBITORS OF ANGIOGENESIS
- Its mechanism of action is unclear.
- Inhibits synthesis of TNF-α.
- Inhibits angiogenesis.
- Thalidomide is now called an immunomodulatory drug.
- Indicated for the treatment of patients with erythema nodosum leprosum and multiple myeloma
7
Q
CYTOTOXIC AGENTS
A
ANTIMETABOLITES
- Azathioprine
- Methotrexate
- Mycophenolate mofetil
- Leflunomide
ALKYLATING AGENTS
- cyclophosamide
8
Q
AZATHIOPRINE including drug interactions
A
- Prodrug of 6-mercaptopurine.
- 6-MP is metabolized to 6-thioinosinic acid,which inhibits de novo purine nucleotide synthesis.
- This leads to suppression of B and T cell function, of immunoglobulin production and of IL-2 secretion
Drug interactions
- Much of the drug’s inactivation depends on xanthine oxidase.
- Patients who are also receiving allopurinol for control of hyperuricemia should have the dose of azathioprine reduced.
- Azathioprine is indicated for prevention of organ transplant rejection and in severe rheumatoid arthritis.
9
Q
METHOTREXATE
A
MOA @ low doses
- inhibition of amino imidazole carboxamide ribonucleotide (AICAR) transformylase.
- AICAR transformylase catalyzes the penultimate and final steps in de novo purine biosynthesis which lead to synthesis of IMP.
- Inhibition of AICAR transformylase leads to accumulation of AMP.
- AMP is released and converted extracellularly to adenosine
- Adenosine is a potent inhibitor of inflammation.
10
Q
MYCOPHENOLATE MOFETIL
A
- Mycophenolate mofetil is converted into mycophenolic acid.
- Mycophenolic acid inhibits inosine monophosphate dehydrogenase, an enzyme in the de novo pathway of GTP synthesis.
- This action suppresses both B-andT- lymphocyte activation.
- Lymphocytes are particularly susceptible to inhibitors of the de novo pathway because they lack the enzymes necessary for the salvage pathway.
Uses
- Prophylaxis of transplan trejection.
- SLE
11
Q
LEFLUNOMIDE
A
- Prodrug of teriflunomide.
- Teriflunomide inhibits dihydroorotate dehydrogenase.
- This decreases levels of UMP.
- UMP is essential for the synthesis of pyrimidines.
Uses
- Rheumatoid arthritis
- SLE
- Myasthenia gravis
12
Q
Cyclophosphamide
A
- ALKYLATING AGENTS
- one of the most effective immunosuppressive drugs available.
- Cyclophosphamide destroys proliferating lymphoid cells.
**Uses: **SLE and other autoimmune diseases.
13
Q
POLYCLONAL ANTIBODIES
A
- Antilymphocyte & Antithymocyte Antibodies
- Immune Globulin Intravenous (IGIV)
- Rho(D) Immune Globulin
- Hyperimmune Immunoglobulins
14
Q
ANTILYMPHOCYTE & ANTITHYMOCYTE ANTIBODIES
A
- Antilymphocyte globulin (ALG)
- Antithymocyte globulin (ATG)
- Both are produced in horses or sheep by immunization against human thymus cells.
- Antibodies in these preparations bind to T cells involved in antigen recognition and initiate their destruction by serum complement.
Uses
- ALG and ATG are used before stem cell transplantation to prevent graft-versus-host reaction.
- Also used for solid organ transplantation.
15
Q
IGIV
A
- Immunoglobulin preparation from pools of thousands of healthy donors.
- It is believed to have a normalizing effect on an individual’s immune system.
- Its precise mechanism is not known.
Uses
- Immunoglobulin deficiencies
- Autoimmune disorders
- HIV disease
- Bone marrow transplantation
