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
16
Q
HYPERIMMUNE IMMUNOGLOBULINS
A
Available for treatment of:
- RSV
- Cytomegalovirus
- Varicella zoster
- Hepatitis B virus
- Rabies
- Tetanus
- Rattlesnake and coral snake bites
- Digoxin overdose
17
Q
TNF-α INHIBITORS
A
include Infliximab & Etanercept
Risks
- Patients may be at an increased risk of infection or reactivation of M tuberculosis, hepatitis B virus, and invasive systemic fungi.
- Patients may also be at increased risk for malignancies.
18
Q
INFLIXIMAB
A
- Chimeric monoclonal antibody.
- Binds with high affinity and specificity to human TNF-α
- Used in the treatment of Crohn’s disease, rheumatoid arthritis, ulcerative colitis, ankylosing spondylitis, and psoriatic arthritis.
19
Q
ETANERCEPT
A
- Not a true Mab.
- Contains the ligand-binding portion of a human TNF-α receptor fused to the Fc portion of human IgG1
- Etanercept binds to TNF-α and prevents it from interacting with its receptors.
- Approved for rheumatoid arthritis, ankylosing spondylitis, plaque psoriasis, polyarticular juvenile idiopathic arthritis, and psoriatic arthritis
20
Q
MUROMONAB-CD3
A
- Binds to the CD3 antigen on the surface of thymocytes and mature T cells.
- Depletes pool of T cells.
- Used to manage acute rejection of kidney, heart and liver transplants.
21
Q
DACLIZUMAB
A
- IL-2receptorantagonist.
- Humanized IgG that binds to the IL-2 receptor present on the surface of activated lymphocytes and prevents activation by IL-2.
- Used in combination with other immunosuppressants to prevent renal transplant rejection.
22
Q
BASILIXIMAB
A
- IL-2 receptor antagonist.
- Chimeric human-mouse IgG.
- Binds to the IL-2receptor.
- Used in combination with other immunosuppressants to prevent renal transplant rejection.
23
Q
RITUXIMAB
A
- Chimeric murine-human monoclonal antibody that binds to the CD20 molecule on B lymphocytes.
- Causes depletion of circulating B cells.
- Used for treatment of non-Hodgkin’s lymphoma and chronic lymphocytic leukemia.
- Also approved for the treatment of rheumatoid arthritis.
24
Q
IMMUNOSTIMULANTS
A
- Aldesleukin
- Interferons
- Bacillus Calmette-Guérin (BCG)
25
Q
ALDESLEUKIN
A
- Recombinant interleukin-2 (IL-2).
- IL-2 is a lymphokine that promotes the production of cytotoxic T lymphocytes and activates NK cells.
- Aldesleukin is indicated for the adjunctive treatment of renal cell carcinoma and malignant melanoma.
26
Q
INTERFERONS
A
used in hairy cell leukemia, chronic myelogenous leukemia, malignant melanoma, Kaposi’s sarcoma, and hepatitis B and C infections.
Interferon-β is approved for use in relapsing multiple sclerosis.
Interferon-γ is approved for treatment of chronic granulomatous disease.
27
Q
BCG
A
- Attenuated, live culture of Mycobacterium bovis.
- By unclear mechanisms, it is active against tumors.
- It is indicated for the treatment and prophylaxis of carcinoma of the urinary bladder.
- Adverse effects include hypersensitivity, shock, chills, fever, malaise, and immune complex disease.
