Immunopharmacology Flashcards
Uses of Immunosuppressives?
1) Autoimmune diseases
2) Isoimmune diseases
3) Organ transplantation
4) Prevention of cell proliferation
Classification of Immunosuppressive Agents?
1) Corticosteroids
2) Calcineurin inhibitors
3) Cytotoxic agents
4) Mycophenolate mofetil
5) Proliferative signal inhibitors
6) Biologicals (antibodies)
Steroids are used in the treatment of?
RA SLE Psoriasis Asthma Inflammatory renal disease Inflammatory opthalmic disease Autoimmune hematological disease MS
Immediate side effects of corticosteroids:
Cushingoid features Weight gain (ravenous appetite) Diabetes (transient) Hirsutism (especially pediatrics) Cataracts Mood changes
Corticosteroids are excreted via the ___ as the metabolite ____:
kidneys; dihydroxyketone (17-hydroxysteroids)
Longest acting, most potent corticosteroids?
Bethamethasone
Dexamethasone
Least potent corticosteroid?
Cortisone
Shortest acting corticosteroid?
Hydrocortisone
Long term effects of corticosteroids:
Osteoporosis
Avascular necrosis
Growth retardation
Effects of steroids?
Regulates numerous gene transcription
Curtail NF-KB activation
Downregulation of IL-1 and IL-6
T-cells are inhibited from producing IL-2
CD8 activation is inhibited
Increase in neutrophils, decrease in other leukocytes
Neutrophils and monocytes display poor chemotaxis
The CNI Cyclosporine A is derived from?
Tolypocladium inflatum
The CNI Tacrolimus is derived from?
Streptomyces tsukunbaensis
IC mediator of CsA?
Cyclophilin
IC mediator of TAC?
FKBP-12
Adverse effects unique to CsA?
Hirsutism
Gum hypertrophy
Hypercholesterolemia
Adverse effects unique to TAC?
Hair loss
GI side effects
Adverse effects common to both TAC and CsA?
Nephrotoxicity
Hyperkalemia
Hypomagnesemia
What are the cytotoxic agents?
Azathioprine Methotrexate Cyclophosphamide Leflunomide Hydroxychloroquine
Uses of Azathioprine?
Transplantation RA Crohn's disease Ulcerative colitis GVHD
Methotrexate inhibits____ which leads to ____.
Dihydrofolate reductase; cessation of nucleotide synthesis
Uses of methotrexate?
GVHD
RA
SLE
Psoriasis
Cyclophosphamide is an ____ that forms covalent bonds with DNA and suppresses ___, which inhibits ___ production.
alkylating agent; cellular immunity; Ab and autoAb
Adverse effects of cyclophosphamide:
Leukopenia Sterility Hemorrhagic cysts (hydrate patient before infusion) Malignancy Cardiac toxicity N&V
Uses of cyclophosphamide:
Hematopoietic cell transplantation
SLE
Vasculitis
Wegener’s Granulomatosis
Leflunomide is a pro-drug inhibitor of ___ synthesis and indicated in cases of __:
Pyrimidine; Rheumatoid arthritis
Hydroxychlorine suppresses ___ by ____, which results in decreased ___.
APC processing and MHC II loading; increasing lysosomal pH; T-cell activation
Mycophenolate mofetil reversibly inhibits ____, thereby blocking:
IMDPH; de novo purine synthesis
What are the Proliferative signal inhibitors?
1) Sirolimus/Rapamycin/Rapammune
2) Everolimus
3) Temsirolimus
Sirolimus is a ____ derived from __.
Macrocylic lactone; streptomyces hygroscopicus
Azathiprine is metabolized to ___, which interrupts ___ and so reduces mitosis.
6-mercaptopurine; purine synthesis
Adverse effects of MMF:
GI disturbances
Suppression of bone marrow
Long term risks of Aza therapy:
Increased risk of squamous cell carcinoma
Lymphoma
Bacterial and opportunistic infections
MOA of Sirolimus?
1) Binds to FKBP
2) Blocks serine threonine kinase
3) Does not block IL production but lymphocytic response to them.
Everolimus is a ____ derived from naturally occurring ___.
Semi-synthetic proliferative signal inhibitor (PSI); rapamycin
TAC is 50 -100 more potent than ___; but ___ is 27x more potent than TAC
CsA; Sirolimus
Sirolimus is isolated from:
Streptomyces hygroscopicus
Sirolimus arrests malignant cell growth through it’s ____ effect:
anti-angiogenesis
Mechanism of the ATGs?
Depletion of circulating t-cells
Modulation of cell surface receptor molecule
Induction of anergy
Apoptosis of activated T-cells
MMF is not co-administered with:
Azathioprine
What is the first therapeutic monoclonal antibody? What is it’s antigen?
OKT3, directed against CD3 receptor on T cells
Symptoms of cytokine release syndrome:
First dose effect
Fever, chills, rigors, “shake and bake”
Pulmonary edema
This drug has a low rejection rate and minimal side effects when used in kidney transplant:
Alemtuzumab
Chimeric mAb IL-2 Receptor antagonist:
Basiliximab
Humanized mAb IL-2 receptor antagonist:
Daclizumab
Rituximab is a ___ mAb specific for the B-cell marker ___, approved in the treatment of:
chimeric; CD20; refractory non-Hodgkins lymphoma
Alemtuzumab is a ___ mAb directed against the marker ___:
Humanized; CD52
Restores function of B & T lymphocytes, monocytes and macrophages:
Levamisole
Indicated in erythema nodosum leprosum multiple myeloma RA:
Thalidomide
Used in Ca in situ of the urinary bladder and primary recurrent papillary tumors:
Bacille-Calmette-Guerin
Indications for Interferon Alpha-2b:
Chronic Hep B and C
Melanoma
Lymphoma follicular
Kaposi’s sarcoma
Interferon indicated in multiple sclerosis:
Interferon Beta-1a
The Recombinant cytokines:
Hematopoietic growth factors
Interferons
Interleukin-2 (RCC)
The therapeutic Abs:
IVIG (polyclonal) Polyclonal Ab (directed against cells) Hyperimmune globulins (polyclonal and monoclonal)
Used to treat Rh disease:
Polyclonal Ab, RhD immunoglobulin against the D blood group Ag
The hyperimmuneglobulins:
Hep B Immuneglobulin Rabies Tetanus Varicella CMV RSV
Immunomodulator used in metastatic renal cell carcinoma?
IL-2
