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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

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
Q

Average adult has a total storage pool of ____

A

3-5mg

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26
Q

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

A

Distal ileum

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27
Q

Serves as intermediate in the transfer of methyl group of N-methyltetrahydrofolate to homocysteine, forming methionine

A

Methylcobalamin

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28
Q

Disruption of ____ is thought to be the cause of the neurologic manifestations of Vitamin B12 deficiency

A

Methionine synthesis pathway

29
Q

Isomerization of methylmalonyl-CoA to _______ by the enzyme _____

A

Succinylcholine-CoA

Methylmalonyl-CoA mutase

30
Q

Accumulation of folate as N-methyltetrahydrofolate and the associated depletion of tetrahydrofolate cofactors in vitamin B12 deficiency

A

Methylfolate trap

31
Q

Determine whether the cause of megaloblastic anemia is due to B12 deficiency or folic acid def

A

Serum levels of vitamins

32
Q

Measures absorption and urinary excretion of radioactively labeled vitamin B12
Used to defined the mechanism of V12 malabsorption

A

Schilling test

33
Q

Most common causes of V12 deficiencies

A

Pernicious anemia (defective secretion of IF and individuals frequently have autoantibodies for IR)
Partial or total gastrectomy
Conditions affecting distal ileum

34
Q

Parenteral injection is available as ___

A

Cyanocobalamin or hydroxycobalamin

35
Q

Preferred because it is highly protein-bound and remains longer in the circulation

A

Hydroxycobalamin

36
Q

Initial therapy for V12 def

A

100-1000 micrograms IM daily or every other day for 1-2 weeks

37
Q

Maintenance therapy for V12 def

A

100-1000 micrograms IM once a month for life

38
Q

Required for essential biochemical reactions that provide precursors for the synthesis of AA, purines and DNA

A

Folic acid

39
Q

Indicated in the cause of congenital NTD

Relatively common

A

Folic acid deficiency

40
Q

Folic acid deficiency can be caused by drugs

A

Methotrexate
Trimethroprim and pyrimethamine
Phenytoin

41
Q

Inhibits dihydrofolate reductase and may result in a deficiency of folate cofactors

A

Methotrexate

42
Q

Long-term use may also cause folic acid deficiency

Rarely causes megaloblastic anemia

A

Phenytoin

43
Q

Dose for treating folic acid deficiency

A

1 mg orally

44
Q

Gp (34-39 kDa)

Serum half-life of 4-13 hours in px with chronic renal failure

A

EPO

45
Q

Modified form of EPO that is more heavily glycosylated resulting to a twofold to three fold longer half-life than epoetin alfa

A

Darbepoetin alfa

46
Q

Isoform of EPO covalently attached to a long polyethylene glycol polymer administered at 2-week or monthly intervals

A

Methoxypolyethylene glycol-epoeitin beta

47
Q

EPO receptor is a member of ____

Use phosphorylation and transcription factor activate to regulate cellular function

A

JAK/STAT cytokine receptors

48
Q

Adverse effects of EPO

A

HPN
Thrombotic complications
Allergic reactions
Pure red cell aplasia

49
Q

Consistently improve hematocrit and hemoglobin level

Often eliminate the need of transfusion

A

Erythropoiesis-stimulating agents (ESAs)

50
Q

Originally purified from cultured human cell lines

A

G-CSF

GM-CSF

51
Q

Covalent conjugation product of filgastrim and a form of polyethylene glycol
Longer serum half -life than recombinant G-CSF

A

Pegfilgrastim

52
Q

Glycosylated form of recombinant G-CSF

A

Lenograstim

53
Q

Stimulates progenitors committed to neutrophil lineage

Activates phagocytic activity of mature neutrophils and prolongs their survival

A

G-CSF

54
Q

Multipotential hematopoeitic growth factor
Stimulates proliferation and differentiation of earlly and late granulocytic progenitor cells, and erythroid and megakaryocyte progenitors

A

GM-CSF

55
Q

Also mobilizes PB stem cells, but significantly less efficatious and more toxic

A

GM-CSF

56
Q

Common adverse effect of the cytotoxic drugs used to treat cancer, and they increase the risk of serious infection in patients receiving chemotherapy

A

Neutropenia

57
Q

Treatment regimen for neutropenia

A

G-CSF

58
Q

Can be an alternative to preventing chemotherapy-induced neutropenia
Administered once per chemotherapy cycle
Shortens period of severe neutropenia slightly more than G-CSF

A

Pegfilgrastim

59
Q

Potent hematopoietic stem cell mobilizer

A

Plerixafor

60
Q

Key endogenous regulators of platelet production

A

TPO and IL-11

61
Q

TPO agonists

A

Romiplostim

Eltrombopag

62
Q

68-85 kDa protein produced by fibroblasts and stromal cells in the bone marrow
Half-life is 7-8 hours

A

IL-11

63
Q

Recombinant form of IL-11 approved for medical use and is produced by expression in E. coli

A

Oprelvekin

64
Q

Acts through a specific cell surface cytokine receptor to stimulate the growth of multiple lymphoid and myeloid cells

A

IL-11

65
Q

Approved for the secondary prevention of thrombocytopenia in px receiving cytotyoxic chemotherapy for treatment of nonmyeloid cancers

A

IL-11

66
Q

IL-11 dosing

A

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
Q

Approved for therapy for patients with chronic immune thrombocytopenia and inadequate response to other therapies

A

Romiplostim

68
Q

After subcutaneous administration, romiplostim is eliminated by the ____ with an average half life of ____

A

RES

3-4 days

69
Q

Orally active small nonpeptide thrombopoeitin agonist

For tx of thrombocytopenia in patients with hep C to allow initiation of IFN therapy

A

Eltrombopag

Basic Pathology 2 (8 decks)

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