6. hematopoietic colony stimulating factors Flashcards
what are the three types of leukocytes that are granulocytes
- neutrophils
- basophils
- eosinophils
what are the two leukocytes that don’t have granulocytes in their cytoplasm
- lymphocytes (B and T lymphocytes)
- monocytes (macrophages)
what are the major functions of blood
- transport of oxygen and carbon dioxide, food molecules (e.g. glucose, lipids amino acids), ions, hormones and other biochemical modulators, wastes, heat
- defence against infections and other foreign materials
- homeostasis, a process by which bleeding is halted
blood cells are produced in the _________
bone marrow
blood cells arise from a single type of cell called a ______________
hematopoietic stem cell
these factors play a role in the formation of blood cells
hematopoietic colony stimulating factors
this is a blood disorder defined as a qualitative or quantitative deficiency of hemoglobin
anemia
acute myelogenous _______, chronic lymphocytic _______ and chronic granulocytic __________ are all types of what bleeding disorder
leukemia
polycythemia, multiple myeloma, aplastic anemia and agranulocytosis are all different types of
bone marrow disorders
this stimulates the production of RBC.
- bleeding and higher demand for oxygen triggers increased production of ______.
- it is used in the treatment of anemia associated with chronic renal failure for patients on dialysis
- may also be used in anemia caused by other drugs
- anemia caused by cancer chemotherapy
- severe blood loss in certain populations such as Jehovahs witness, whose religion forbids them to receive blood transfusions
erythropoietin (EPO)
this medication is recombinant EPO. it is a 165 amino acid glycoprotein. it is a sterile, colorless formulation for i.v. or s.c. injection.
- doping substance used in sports
EPOGEN
this medication is an erythropoiesis stimulating protein, closely related to eryhtropoeitin. it is a 165 amino acid protein produced in Chinese hamster ovary cells by recombinant DNA.
- is formulated as a sterile, colorless, preservative free protein solution for iv or sc administration
is indicated for the treatment of
- anemia associated with chronic renal failure, including patients on dialysis and patents not on dialysis
- anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy
Aranesp
how to Aranesp and EPOGEN differ?
-EPOGEN contains 3 N-linked oligosaccharide chains
- Aranesp contains 5 chains
two additional N-glycosylation sites result from amino acid substitutions in the erythropoietin peptide backbone
does Darbepoetin alpha or recombinant human erythropoietin (rHu-EPO) have a longer half life?
darbepoetin alpha
does Darbepoetin alpha or recombinant human erythropoietin (rHu-EPO) have a larger clearance
rHu-EPO
does Darbepoetin alpha or recombinant human erythropoietin (rHu-EPO) have a larger AUC
Darbepoetin alpha
does Darbepoetin alpha or recombinant human erythropoietin (rHu-EPO) have a larger Vd?
rHu-EPO
this medication is methoxy polyethylene glycol (MPEG) attached to the -NH2 of N-terminus and all lysine side groups (longer circulation half life). it is a new continuous erythropoietin receptor activator (CERA).
Once a month injection maintains stable Hb levels
Mircera
this medication is a granulocyte colony-stimulating factor, a recombinant version of a human protein. selectively stimulates the production of infection fighting white blood cell (neutrophil). it is used to decrease the incidence of infection in certain cancer treatments
- it is a 175 amino acid protein expressed by E.coli bacteria into which the human granulocyte colony-stimulation factor gene has been inserted
- addition of an N-terminal Met is necessary for the expression of E.coli
indicated for:
- cancer patients receiving myelosupressive chemotherapy
- patients with acute myeloid leukemia receiving induction or consolidation chemotherapy
- cancer patients receiving bone marrow transplant
- patients undergoing peripheral blood progenitor cell collection and therapy
- patients with severe chronic neutropenia
NEUPOGEN (filgrastim)
this medication has a longer half life than NEUPOGEN (filgrastim). has a half life from 15 to 80 hours after s.c. injection
- approved for chemotherapy-induced neutropenia
Neulasta (pegfilgrastim)
this medication is a recombinant granulocyte-macrophage colony-stimulating factor (rHu-GM-CSF)
- can accelerate myeloid recovery, including increase in the number and activity of neutrophils, monocytes/macrophages and myeloid derived dendritic cells
this medication enhances immune stimulation which is important for
- antibacterial activity
- anti fungal activity
- antiviral activity
- in vitro antitumor activity
it is used following chemotherapy in older patients with acute myelogenous leukemia to speed up the recovery of the neutrophils and to reduce the incidence of severe and life threatening infections
it is also used in multiple stem cell transplantation settings
Leukine
this is a generic term for a large group of low molecular weight immune system proteins secreted by different cell types that act as chemical messengers
they enhance cell growth, promote cell to cell communication, coordinate antibody and T cell immune interactions, amplify immune reactivity
cytokines
list some types of cytokines
colony-stimulating factors
lymphokines’
chemokines
interleukins
interferons
tumor necrosis factors
these are a group of cytokines (secreted signalling molecules). they were first seen to be expressed by WBCs
interleukins
this medication is classified as a biological response modifier. BRMs modify the body response to cancer cells. it helps increase the production of several different components of the immune system in the blood (e.g. t lymphocytes and natural killer cells).
it is a synthetic form of IL-2. it is used for
- metastatic renal cell carcinoma
- metastatic melanoma
PROLEUKIN IL-2 (Aldesleukin)
did patients respond to low dose or high dose intravenous interleukin 2
high dose
this medication is a thrombopoietic growth factor (TPO). it directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells, induces megakaryocytic maturation resulting in an increased platelet production.
it is produced in E.coli by recombinant DNA technology
it is indicated for:
-the prevention of severe thrombocytopenia
-the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in adult patients with nonmyseloid malignancies who are at high risk of severe thrombocytopenia
Neumega (oprelvekin) IL-11
Neumega (oprelvekin) IL-11 is 177 amino acids in length and differs from the 178 amino-acid length of native IL-11 only in lacking the amino-terminal _____ residue, which is a potential alpha-helical breaker
proline
what is the ph of Neumega (oprelvekin) IL-11
7.0
a class of natural proteins produced by immune cells in response to challenges by foreign agents such as viruses, bacteria, parasites, and tumour cells
biological properties include:
- antiviral and antioncogenic properties
- macrophage and natural killer lymphocyte activation
- enhancement of major histocompatibility complex (MHC) glycoprotein classes I and II thus presentation of foreign antigens to T cells
interferons
what receptor do interferon type I bind to
binding to a specific cell surface receptors complex known as the IFN-alpha receptor (IFNAR)
what receptor do interferon type II bind to
binding to the IFN-gamma receptor
what receptor do interferon type III bind to
binding to a receptor complex consisting of IL10R2 and IFNLR1
this type of interferons are secreted by many cell types including lymphocytes (NK cells, B-cells and T-cells), macrophages, fibroblasts, endothelial cells, osteoblasts and others
stimulate both macrophages and NK cells to elicit an anti-viral response
also active against tumours
type I IFNs (alpha and beta)
this type of interferons are released by leukocytes at the site of the viral infection or tumors
type I IFNs (w)
this type of interferons are produced in activated T cells and NK cells.
possess weak anti-vital and anti-tumor effects
potentiate the effects of the type I IFNs
type II IFNs
this interferon medication is interferon alpha-2a and is used for hairy cell leukemia, AIDS related Kaposi’s sarcoma, hep. C.
Roferon-A
this interferon medication is interferon alpha-2a which can be used alone or in combination with Ribavirin, an antiviral agent
used to treat hep. b and c.
pegylated therefore it has an increased half life
Pegsys
this interferon medication is interferon alpha-2b
is used to treat hairy cell leukemia, genital warts, hep b and c, malignant melanoma
Intron A
this interferon medication is interferon alpha-n3
approved for the treatment of genital and perianal warts caused by HPV
Alferon-N
this interferon medication is interferon beta-1b which is approved for the treatment on MS
Betaseron
this interferon medication is interferon beta-1a and is approved for the treatment of MS
Avonex
what are some common side effects of interferons
- flu like symptoms
- convulsion
- hair thinning
- depression
- erythema, pain and hardness at the injection site
