drugs for growth factors ch55

8/3/2019 Drugs for Growth Factors Ch55

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Chapter 55Chapter 55

Hematopoietic Growth FactorsHematopoietic Growth Factors


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DRUGS FOR

HEMATOPOIESIS


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OVERVIEW OF BLOOD Blood is essential for cell survival

Contains oxygen and nutrients

Removes waste products that could be toxic to

the tissues Contains clotting factors that help maintain

the vascular system

Contains the important components of theimmune system

Process of blood cell formation is calledhematopoiesis which begins with a stem cell


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OVERVIEW (cont.) The differentiation of the cell depends on the

needs of the body

Regulation occurs through hormones & chemicals

Hematopoietic Growth Factors: Erythropoietic or Erythropoiesis Stimulating Agents

Leukopoietic or Colony-Stimulating Factors

Thrombopoietic Through recombinant DNA technology, some of

these growth factors are available to be used as

medications


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ERYTHROPOIESIS

Process ofRBC production

RBCs are produced in the myeloid tissue of

bone marrow

The rate ofRBC production is controlled by

the glycoprotein erythropoietin

This protein is released from the kidneys in

response to decreased blood flow ordecreased oxygen tension in the kidneys

An undifferentiated cell is a hemocytoblast


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ERYTHROPOIESIS (cont.)

In the last phase, the cell loses its nucleus and

enters the circulation as a reticulocyte where it

finishes the maturing process

Due to the lack of a nucleus, the RBC cannot

reproduce or maintain itself

The average lifespan of an RBC is about 120

days

The old RBC will then be lysed in the liver,

spleen or bone marrow


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Hematopoietic Growth FactorsHematopoietic Growth Factors

Process by which blood cells and platelets areProcess by which blood cells and platelets are

producedproduced

TypesTypes Hematopoietic growth factorHematopoietic growth factor

Erythropoietic (RBCs)Erythropoietic (RBCs)

Leukopoietic (WBCs)Leukopoietic (WBCs)

Thrombopoietic growth factorThrombopoietic growth factor Oprelvekin (platelets)Oprelvekin (platelets)


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ERYTHROPOIETIC GROWTH FACTORS

Protype: epoetin alfa (Epogen, Procrit)

Drug formulation of erythropoietin

Therapeutic Uses:

Treats anemia associated with chronic renal failure

Decreases the need for blood transfusions in anemic

patients undergoing surgery

Treats anemia related to treatment for AIDS Chemotherapy-Induced Anemia (Procrit)

Administered IV or SQ (preferred route)


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Erythropoietic Growth FactorsErythropoietic Growth Factors

Also known as ESAs (erythropoiesisAlso known as ESAs (erythropoiesis

stimulating agents)stimulating agents)

Adverse effectsAdverse effects Increased risk ofDVT when used prior to electiveIncreased risk ofDVT when used prior to elective

surgerysurgery

For patients with cancerFor patients with cancer Can shorten time to tumor progressionCan shorten time to tumor progression

Reduce overall survivalReduce overall survival


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ERYTHROPOIETIC GROWTH FACTORS (cont.)

Adverse Effects:

Autoimmune Pure RBC Aplasia

Hypertension/Heart Failure

Thrombotic Events Administered 3 times/week until therapeutic response is

reached

Contraindicated for anemic patients that have normal

renal function

darbepoetin alfa (Aranesp) is pharmacologically similar

to Epogen & Procrit; however, the duration of action is

longer


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Epoetin Alfa (Erythropoietin)Epoetin Alfa (Erythropoietin)

Brand namesBrand names Epogen, ProcritEpogen, Procrit Hematopoietic growth factorHematopoietic growth factor

Significant effects outside hematopoietic systemSignificant effects outside hematopoietic system

Recombinant DNA technologyRecombinant DNA technology

UsesUses Anemia associated with chronic renal failureAnemia associated with chronic renal failure

For HIVFor HIV--infected patients taking zidovudineinfected patients taking zidovudine

ChemotherapyChemotherapy--induced anemiainduced anemia

Anemia in patients facing surgeryAnemia in patients facing surgery


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Adverse effectsAdverse effects HypertensionHypertension

Autoimmune pure redAutoimmune pure red--cell aplasiacell aplasia Very rareVery rare

Cardiovascular eventsCardiovascular events Cardiac arrestCardiac arrest

HypertensionHypertension

Heart failureHeart failure Thrombotic events (stroke and MI)Thrombotic events (stroke and MI)


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DosageDosage

To minimize risksTo minimize risks

Use minimum needed to gradually raise hemoglobinUse minimum needed to gradually raise hemoglobin

content to eliminate the need for RBC transfusionscontent to eliminate the need for RBC transfusions

Hemoglobin level should not exceed 12 g/dLHemoglobin level should not exceed 12 g/dL

MonitoringMonitoring

Monitor hemoglobin level twice weeklyMonitor hemoglobin level twice weekly


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LongerLonger--Acting ErythropoietinsActing Erythropoietins

Darbepoetin alfa (longDarbepoetin alfa (long--acting)acting) Similar risks and needs for monitoring as epoetinSimilar risks and needs for monitoring as epoetin

alfaalfa

Patients with hypertension may need increasedPatients with hypertension may need increasedhypertension medshypertension meds

Methoxy polyethylene glycolMethoxy polyethylene glycol epoetin betaepoetin beta

(very long(very long--acting)acting) Not marketed in the United StatesNot marketed in the United States


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COLONY-STIMULATING FACTORS

Increases the production of leukocytes andactivates existing WBCs

Active at very low concentrations

Named according to the type of blood cell theystimulate

G-CSF--Prototype: filgrastim (Neupogen)

Neutrophils

GM-CSFPrototype: sargramostim (Leukine)

Neutrophils Monocytes Macrophages -

Eosinophils


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COLONY-STIMULATING FACTORS

(cont.)

Made through recombinant DNA technology

Indications for Use:

Prevent infection in patients with neutropeniainduced by cancer chemotherapy or bone

marrow transplantation

To mobilize stem cells from the bone marrowto the periphery to be reinfused after

chemotherapy

To treat severe chronic neutropenia


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Filgrastim (Neupogen)Filgrastim (Neupogen)

Granulocyte colonyGranulocyte colony--stimulating factorstimulating factor Leukopoietic growth factorLeukopoietic growth factor


Reduces the incidence of severe neutropeniaReduces the incidence of severe neutropenia Produces doseProduces dose--dependent increase independent increase in

circulating neutrophilscirculating neutrophils

Reduces the incidence of infection, need forReduces the incidence of infection, need forhospitalization, and need for intravenoushospitalization, and need for intravenous

antibioticsantibiotics


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Filgrastim (Neupogen)Filgrastim (Neupogen)

UsesUses CancerCancer

Severe chronic neutropeniaSevere chronic neutropenia

Adverse effectsAdverse effects Bone painBone pain

LeukocytosisLeukocytosis


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Pegfilgrastim (Granulocyte ColonyPegfilgrastim (Granulocyte Colony--

Stimulating Factor)Stimulating Factor)

LongLong--actingacting

Derivative of filgrastim (Neupogen)Derivative of filgrastim (Neupogen)

Stimulates myeloid cells to increaseStimulates myeloid cells to increase

production of neutrophilsproduction of neutrophils

Adverse effectsAdverse effects Similar to filgrastimSimilar to filgrastim

May require opioids for pain reliefMay require opioids for pain relief


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Sargramostim (GranulocyteSargramostim (Granulocyte--MacrophageMacrophage

ColonyColony--Stimulating Factor)Stimulating Factor)

Brand nameBrand name LeukineLeukine Hematopoietic growth factorHematopoietic growth factor


UsesUses Adjunct to autologous bone marrowAdjunct to autologous bone marrow

transplantationtransplantation

Treatment of failed bone marrow transplantsTreatment of failed bone marrow transplants

Patients with acute myelogenous leukemia (AML)Patients with acute myelogenous leukemia (AML)

Adverse effectsAdverse effects LeukocytosisLeukocytosis

ThrombocytosisThrombocytosis


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THROMBOPOIETIC GROWTH FACTOR

Stimulates the production of megakaryocytes andthrombopoietin

Prototype: oprelvekin (Neumega)

Used in chemotherapy-induced thrombocytopenia

Delayed onset of action/Extended duration of action

Therapy continues until platelet count returns to

>100,000/mm

Given only using the SQ route

Primary adverse reactions:

Fluid Retention - Cardiac Dysrhythmias Allergic

Reactions


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Oprelvekin (InterleukinOprelvekin (Interleukin--11)11)

Brand nameBrand name NeumegaNeumega Thrombopoietic growth factorThrombopoietic growth factor


UsesUses Used with myelosuppressive chemotherapy to minimizeUsed with myelosuppressive chemotherapy to minimize

thrombocytopenia and to decrease the need for plateletthrombocytopenia and to decrease the need for platelet

transfusionstransfusions

Adverse effectsAdverse effects Fluid retentionFluid retention

Cardiac dysrhythmiasCardiac dysrhythmias

Effects on the eyeEffects on the eye

Sudden deathSudden death


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Important Points

Do not administer this drug simultaneously withchemotherapy

Monitor cardiac status

Monitor CBC with differential twice weekly Assess for skeletal pain

Contraindicated in those with hypersensitivity to E. Coli

A serious side effect of Leukine is respiratory distress

that occurs during the first time the drug is

administered intravenously

Teach patient to avoid people with infections/crowds


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CAUTIONCAUTION

Epoetin alfa, filgrastim, sargramostim, andEpoetin alfa, filgrastim, sargramostim, and

oprelvekin stimulate proliferation of boneoprelvekin stimulate proliferation of bone

marrow cellsmarrow cells

USE WITH GREAT CAUTION, if at all, forUSE WITH GREAT CAUTION, if at all, for

patients with cancers of bone marrow originpatients with cancers of bone marrow origin


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drugs for growth factors ch55

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