Pharmacology and Pharmacotherapy of Neutro/Thrmbocytopenia Flashcards
What is neutropenia?
Granulocye disorder with low number of neutrophils
Mild neutropenia is?
1000-1500
Minimal risk of infection
Moderate neutropenia is?
500-1000
Moderate risk of infection
Severe neutropenia is?
<500
Severe risk of infection
What is thrombocytopenia?
Decrease in platelets within the blood
<100,000
Decreased platelet count due to?
Decreased production
Increased destruction
Drug-induced
What are hematopoietic growth factors?
Glycoproteins that are secreted from bone marrow cells and peripheral tissue
ACTIVE AT LOW CONCENTRATIONS
Interact synergistically with other factors
Proteins produced in prokaryotes show?
No glycosylation
Proteins produced in eukaryotic cells are?
glycosylated
Degree of glycosylation can affect?
PK
Biological activity
Antigenicity
Toxicity
What stimulates stem cells to form a series of burst-forming units (BFU) and colony forming units (CFU)?
Stem cell factor
FLT-3 ligand
IL3
GM-CSF
What is SCF
Cytokine/Hematopoietic Growth Factor involved in regulation in the early stages of hematopoiesis
- Promote HSC survival and self-renewal
SCF exerts its effects by binding to what receptor?
CD117
SCF bind with its receptors creates?
Docking sites for signal transduction molecules
ANCE STIM
Soluble SCF
What is Granulocyte- Colony Stimulating Factor (G-CSF)?
GF that stimulates proliferation and differentiation of colony forming unit committed to the neutrophil lineage
What does G-CSF do?
Protect neutrophils from apoptosis and enhances their function
Control migration from marrow to the blood
Filgrastim
Recombinant G-CSF
Treat severe neutropenia
NOT in prego
Pegfilgrastim (Neulasta)
Pegylated recombinant G-CSF
Minimize glomerular filtration = increased duration of action
Granulocyte Macrophage-CSF
Stimulates production and activty of all granulocytes and monocytes
Lineage specific receptor
Sargramostim (Leukine)
Recombinant GM-CSF
Less glycosylated
Treats: after bone marrow transplant or neutropenia-induced chemotherapy
Molgramotim
Non-glycosylated GM-CSF
Increased receptor binding
Remove carb moiety =
increased the activity of GM-CSF
What does IL11 do?
Stimulates hematopoiesis (megakarlocyte maturation) Improve platelet recovery after chemo
IL11 binds what to do what?
gp130 to initiate signal transduction pathway
What is Oprelvekin (Neumega)?
Non-glycosylated
Stimulates megakaryocytopoiesis and thrombopoiesis
Oprelvekin (Neumega) indicated for?
Prevent severe thrombocytopenia
Reduction of platelet transfusion
- Can cause some heart probs (elderly)
What does Thrombopoietin do?
Stimulates the production and differentiation of megakaryocyte
Romiplostim (Nplate) is?
Fusion protein analog of thrombopoietin (increase platelets)
Romiplostim (Nplate) is indicated for?
Treatment for chronic idiopathic thrmbocytopenic purpura ITP)
Eltrombopag (Promacta) is?
ORAL ONLY
Increases megokaryocytes to platelet
Treats: ITP and Hep C
HEPATOTOXICITY
Erythropoietin (EPO) is?
Prevents apoptosis of erythroid precursor cells
Erythropoietin can cause?
Iron deficiency, hypertension
Epoietin Alpha (Epogen)
Taken with iron supps
Recombinant Erytropoietins
