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Basic Pathology 2 > 23 Agents used in Cytopenias: Hematopoietic Growth Factors > Flashcards

23 Agents used in Cytopenias: Hematopoietic Growth Factors Flashcards

(69 cards)

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1
Q

Three essential nutrients for hematopoiesis

A

Iron
V B12
Folic acid

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2
Q

Proteins that regulate the proliferation and differentiation of hematopoeitic cells

A

Hematopoietic growth factors

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3
Q

Nonheme iron in food and in inorganic iron salts must be reduced by _____ to ____ before it can be absorbed by intestinal mucosal cells

A

Ferric reductase

Ferrous iron

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4
Q

Absorption of iron takes place in the _____

A

Duodenum and proximal jejunum

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5
Q

Iron crosses the luminal membrane of the intestinal mucosal cell by two mechanisms

A

Active transport of ferrous iron by divalent metal transporter (DMT1)
Absorption of iron complexed with heme

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6
Q

Actively transports newly absorbed iron into the blood across the basolateral membrane

A

Ferroportin

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7
Q

Oxidizes iron to ferric iron

A

Feroxidase hephaestin

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8
Q

Iron is stored primarily as _____ in macrophages in the liver, spleen and bone and parenchymal liver cells

A

Ferritin

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9
Q

Controls mobilization of iron from macrophages and hepatocytes
Inhibits intestinal cell iron release by binding to ferroportin and triggering its internalization and destruction

A

Hepcidin

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10
Q

Most common cause of IDA in adults

A

Blood loss

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11
Q

Ferrous salts

A

Ferrous sulfate/gluconate/fumarate

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12
Q

Amount of elemental iron should be given daily to correct IDA most rapidly

A

200-400 mg

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13
Q

Treatment of iron should be continued for _____ to ensure stores are replenished

A

3-6 months

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14
Q

Contains 50 mg of elemental iron/mL of solution

Given through deep IM injection or IV infusion

A

Iron dextran

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15
Q

Before administering of iron dextran, this should be performed

A

Test dose (risk of hypersensitivity reaction)

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16
Q

Other parenteral iron forms

A

Na ferric gluconate complex

Iron-sucrose complex

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17
Q

Potent iron-chelating compound

Given IV to bind iron that has already been absorbed and to promote its excretion in urine and feces

A

Deferoxamine

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18
Q

Lead to organ failure and death

Excess iron is deposited in heart, liver, pancreas and other organs of the body

A

Hemochromatosis (chronic iron toxicity)

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19
Q

Treatment for hemochromatosis

A 
Intermittent phlebotomy (1 unit of blood/week)
Iron chelation therapy
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20
Q

Oral chelator

A

Deferasirox

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21
Q

Extrinsic factor
Cofactor for several essential biochemical reactions in human
Deficiency leads to megaloblastic anemia, GI symptoms, and neurologic abnormalities

A

Cobalamin

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22
Q

Active forms of Vitamin B12

A

Deoxyadenosylcobalamin

Methylcobalamin

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23
Q

Form of Vitamin B12 found in food sources

To be converted into the active form

A

Cyanocobalamin

Hydroxocobalamin

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24
Q

Normal daily requirement for Vitamin B12

A

2 micrograms

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25
Average adult has a total storage pool of ____
3-5mg
26
IF combines with V12 that is liberated from dietary sources in the stomach and duodenum, and the complex is absorbed in the ___ by a highly selective receptor-mediated transport system
Distal ileum
27
Serves as intermediate in the transfer of methyl group of N-methyltetrahydrofolate to homocysteine, forming methionine
Methylcobalamin
28
Disruption of ____ is thought to be the cause of the neurologic manifestations of Vitamin B12 deficiency
Methionine synthesis pathway
29
Isomerization of methylmalonyl-CoA to _______ by the enzyme _____
Succinylcholine-CoA | Methylmalonyl-CoA mutase
30
Accumulation of folate as N-methyltetrahydrofolate and the associated depletion of tetrahydrofolate cofactors in vitamin B12 deficiency
Methylfolate trap
31
Determine whether the cause of megaloblastic anemia is due to B12 deficiency or folic acid def
Serum levels of vitamins
32
Measures absorption and urinary excretion of radioactively labeled vitamin B12 Used to defined the mechanism of V12 malabsorption
Schilling test
33
Most common causes of V12 deficiencies
Pernicious anemia (defective secretion of IF and individuals frequently have autoantibodies for IR) Partial or total gastrectomy Conditions affecting distal ileum
34
Parenteral injection is available as ___
Cyanocobalamin or hydroxycobalamin
35
Preferred because it is highly protein-bound and remains longer in the circulation
Hydroxycobalamin
36
Initial therapy for V12 def
100-1000 micrograms IM daily or every other day for 1-2 weeks
37
Maintenance therapy for V12 def
100-1000 micrograms IM once a month for life
38
Required for essential biochemical reactions that provide precursors for the synthesis of AA, purines and DNA
Folic acid
39
Indicated in the cause of congenital NTD | Relatively common
Folic acid deficiency
40
Folic acid deficiency can be caused by drugs
Methotrexate Trimethroprim and pyrimethamine Phenytoin
41
Inhibits dihydrofolate reductase and may result in a deficiency of folate cofactors
Methotrexate
42
Long-term use may also cause folic acid deficiency | Rarely causes megaloblastic anemia
Phenytoin
43
Dose for treating folic acid deficiency
1 mg orally
44
Gp (34-39 kDa) | Serum half-life of 4-13 hours in px with chronic renal failure
EPO
45
Modified form of EPO that is more heavily glycosylated resulting to a twofold to three fold longer half-life than epoetin alfa
Darbepoetin alfa
46
Isoform of EPO covalently attached to a long polyethylene glycol polymer administered at 2-week or monthly intervals
Methoxypolyethylene glycol-epoeitin beta
47
EPO receptor is a member of ____ | Use phosphorylation and transcription factor activate to regulate cellular function
JAK/STAT cytokine receptors
48
Adverse effects of EPO
HPN Thrombotic complications Allergic reactions Pure red cell aplasia
49
Consistently improve hematocrit and hemoglobin level | Often eliminate the need of transfusion
Erythropoiesis-stimulating agents (ESAs)
50
Originally purified from cultured human cell lines
G-CSF | GM-CSF
51
Covalent conjugation product of filgastrim and a form of polyethylene glycol Longer serum half -life than recombinant G-CSF
Pegfilgrastim
52
Glycosylated form of recombinant G-CSF
Lenograstim
53
Stimulates progenitors committed to neutrophil lineage | Activates phagocytic activity of mature neutrophils and prolongs their survival
G-CSF
54
Multipotential hematopoeitic growth factor Stimulates proliferation and differentiation of earlly and late granulocytic progenitor cells, and erythroid and megakaryocyte progenitors
GM-CSF
55
Also mobilizes PB stem cells, but significantly less efficatious and more toxic
GM-CSF
56
Common adverse effect of the cytotoxic drugs used to treat cancer, and they increase the risk of serious infection in patients receiving chemotherapy
Neutropenia
57
Treatment regimen for neutropenia
G-CSF
58
Can be an alternative to preventing chemotherapy-induced neutropenia Administered once per chemotherapy cycle Shortens period of severe neutropenia slightly more than G-CSF
Pegfilgrastim
59
Potent hematopoietic stem cell mobilizer
Plerixafor
60
Key endogenous regulators of platelet production
TPO and IL-11
61
TPO agonists
Romiplostim | Eltrombopag
62
68-85 kDa protein produced by fibroblasts and stromal cells in the bone marrow Half-life is 7-8 hours
IL-11
63
Recombinant form of IL-11 approved for medical use and is produced by expression in E. coli
Oprelvekin
64
Acts through a specific cell surface cytokine receptor to stimulate the growth of multiple lymphoid and myeloid cells
IL-11
65
Approved for the secondary prevention of thrombocytopenia in px receiving cytotyoxic chemotherapy for treatment of nonmyeloid cancers
IL-11
66
IL-11 dosing
Subcutaneous injection at a dose of 50 mcg/kg/d Started 6-24 hours after completion of chemotherapy and continued for 14-21 days or until the platelet count passes the nadir
67
Approved for therapy for patients with chronic immune thrombocytopenia and inadequate response to other therapies
Romiplostim
68
After subcutaneous administration, romiplostim is eliminated by the ____ with an average half life of ____
RES | 3-4 days
69
Orally active small nonpeptide thrombopoeitin agonist | For tx of thrombocytopenia in patients with hep C to allow initiation of IFN therapy
Eltrombopag

Basic Pathology 2 (8 decks)

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