Download Therapeutic Agents for the Hematological System

Therapeutic Agents for the
Hematological System
Chapter 26
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Major Components of Blood
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•
•
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⬤ Whole
blood (plasma and cellular
components)
⬤ Plasma proteins (albumin*)
➢
⬤ Platelets
➢
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Osmosis and hydrostatic pressure
(thrombocytes)
Lifespan is 10 days
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IronisabuildingblockforRBCsandwithoutit,anemiaoccurs.
• Erythrocytes,alsoknownasRBCs,arecellsthatcontainhemoglobinandcan
carryoxygentothebody.Leukocytesorwhitebloodcellsareinvolvedin
fightinginfection.
• RBCproduction,orerythropoiesis,takesplaceinthebonemarrowandis
largelydrivenbythehormoneerythropoietinthatisproducedbythe
kidneys.ErythropoietincanbetherapeuticallyusedforpeoplewithlowRBC
countsattributabletokidneyorothermedicalconditions.
• Ironisanimportantandnecessaryfactorfortheproductionofhemoglobin.
Cellular Components of Blood
⬤ Leukocytes
(white blood cells [WBCs])
⬤ Erythrocytes (red blood cells [RBCs])
➢
Contain hemoglobin to carry oxygen
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Bloodmustflowtoorganstocarryoxygenandnutrients,butalsoridthe
bodyofwaste.
Italsotransportscellsoftheimmunesystem.
Hydrostaticpressureisdrivenbythebloodpressuregeneratedbycontraction
oftheheart.
Osmosisisthemovementofwaterdownaconcentrationgradient.
Thebloodcarriesoxygenandnutrientsthroughoutthebody,butitalso
carrieswastesfromthetissuesandorgansthatitsupportstoorganssuchas
thekidneysandliverforelimination.Thebloodadditionallytransportscells
oftheimmunesystemtositesofinfectionandinjury.
Incertaininstances,peoplecanproducelessalbumin,attributabletoliver
diseaseormalnutrition,orlosealbuminfromthebloodstream,attributable
tocertaintypesofkidneydisease.Wheneitherhappens,osmoticpressure
decreases,leadingtotheaccumulationoffluidwithinthetissuesoredema.
Platelets,alsoknownasthrombocytes,areacomponentofthebloodthatis
essentialintheprocessofbloodcoagulation(clotting).
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Withadequatesupplementation,resolutionofsymptomsgenerallyoccurs
within4weeksoftreatment.
• Thedurationofsupplementationdependsontheextentofthedeficiencyand
thecausativefactors.
• PerniciousanemiaiscausedbyavitaminB12deficiencyattributableto
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Common Conditions: Anemia
congenitaloracquireddeficiencyofIF.
• Sicklecellanemiainvolvesabnormalhemoglobinsynthesisandabnormal
RBCshape.
• Ironreplacementtherapyistheprimarytreatmentforiron-deficiency
anemia.Mildanemiamaybetreatedwithdietarychanges,andIVironmay
beadministeredtothoseundergoingchronicdialysis.
⬤ Anemia:
Reduction of RBC numbers
⬤ Common cause of iron deficiency anemia is
blood loss
Symptoms: Fatigue, weakness, shortness of
breath, and pallor
➢ Treatment: Identify source of blood loss, iron
replacement therapy, and dietary changes
➢ Drug treatment: Iron replacement therapy
➢
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Secondarypolycythemia,themostcommonform,occursasaresultofa
physiologicalresponsetohypoxia.
• Primarypolycythemia,alsoknownaspolycythemiavera,isachroniccondition
inwhichthebodyoverproducesRBCs.
• Polycythemiaisanincreaseinthetotalcellmassofthebloodfrequently
causedbyexcessiveRBCproduction.
• Forindividualswithpolycythemiavera,phlebotomyisfrequentlyusedto
reducethebloodvolumeandRBCnumbers.Drugtherapyinpolycythemia
verainvolvestreatmentsthatminimizetheriskofthrombosiswith
myelosuppressiveagents(e.g.,hydroxyurea)and/orantithrombotics(e.g.,
anagrelide).
Polycythemia
⬤ Excessive
⬤ Primary
➢
RBC production
or secondary
Difficulty oxygenating the blood
⬤ Treatment:
Smoking cessation, medical
intervention for chronic obstructive pulmonary
disease (COPD) and heart failure, and
phlebotomy
⬤ Drug treatment: Treatments to minimize risks
of thrombosis with myelosuppressive agents
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Thrombocytopeniahasavarietyofcauses.
• Someofthemostcommoncausesarepregnancy(gestational
thrombocytopenia),drugsideeffects(drug-inducedthrombocytopenia),and
idiopathicthrombocytopenia.Idiopathicmeansofunknowncause.
• Heparin,vancomycin,andphenytoinareallassociatedwithdrug-induced
thrombocytopenia.
• Promactaisathrombopoietin-receptoragonist,whichincreasesplatelet
production.
• Promactaneedstobetakenonanemptystomachatleast1hourbeforeor2
hoursaftermeals.
Low Blood Cell and Platelet Counts
⬤ Agents:
Colony-stimulating factors (CSFs)
⬤ Thrombocytopenia: Low platelet count
⬤ Treatment: Resolution of contributing factors,
transfusions to increase platelet levels, and
activity restrictions
⬤ Drug treatment: Steroid treatment, and
glucocorticoid medication
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Neutropenia
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⬤ Occurs
➢
in conjunction with other conditions
Mild, moderate, or severe
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⬤ Leukopenia:
Low WBC count
⬤ Granulocytopenia: Decreased number of
circulating granulocytes
⬤ Treatment depends on degree of severity;
regular dental care
⬤ Drug treatment: Recombinant growth factors,
and CSFs
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Hematological Cancers
⬤ Leukemia:
WBCs
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Cancerous cells replace normal
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Treat with antimetabolites such as 5-fluorouracil (5FU)
⬤ Antimetabolite
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agents: Prevent cell division
Side effects: Nausea, vomiting, fever, anorexia,
and bone marrow suppression
⬤ Antibiotics:
Bind to DNA and prevent formation
of new cancer cells
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Hematological Cancers (Cont.)
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⬤ Alkylating
agents: Nitrogen mustards and
nitrosoureas
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Methods of action and side effects differ
⬤ Nitrogen
mustards: Used during World War I,
reduce WBCs; had severe side effects
⬤ Nitrosoureas: Used to treat brain cancers
➢
Leukemiaisaformofcancercharacterizedbytheproductionofcancerous
hematopoieticstemcellsthatreplacenormalwhitebloodcellswithinthe
bonemarrow
Bothgeneticsandenvironmentalfactorscancontributetothedevelopment
ofleukemia.Environmentalfactorscanincludeexposuretoradiationand
chemicals,includingradiationandchemotherapeuticagentsusedtotreat
otherformsofcancer.
Thereareseveralformsofleukemia,includingacutelymphoblasticleukemia
(ALL),acutemyeloblasticleukemia(AML),chronicmyeloblasticleukemia
(CML),andlymphocyticleukemia(CLL),amongothers.
Thestructureofantimetabolitesissimilartothatofthebasesinthe
nucleotidesthatformdeoxyribonucleicacid(DNA)strands;however,because
theyarenotidentical,antimetabolitespreventthecompletionofcelldivision
ormitosis.Antimetabolitesareoftenusedtotreatleukemia.Themost
commonsideeffectsincludenausea,vomiting,fever,anorexia,bonemarrow
suppression,andjaundice.
StageIV,ormetastaticcancer,isthemostadvancedformofcancer.
Side effects: Severe emesis, nausea, diarrhea, and
hair loss
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➢
Whenapatientisassessedforneutropenia,theabsoluteneutrophilcount
(ANC)oftenisusedtodefinetheneutropeniaasmild,moderate,orsevere.
Theseagentscanbeusedprophylacticallyforchemotherapy-induced
neutropeniaandfortherapeuticuseinpeoplewithpreexistingneutropenia.
Granulocytopeniaisareductioninthenumberofgranulocytes,which
encompassesspecifictypesofwhitebloodcellsinthebloodthatcontain
granules.Thesewhitebloodcellsincludeneutrophils,eosinophils,and
basophils;allareknownasgranulocytes.
Neupogenstimulatestheproductionofneutrophilsinthebonemarrowand
isusedtotreatneutropenia.Itissuppliedasasubcutaneousinjectionand
shouldnotbeshakenbeforeadministration.
Circulatinggranulocytesareneutrophils,eosinophils,andbasophils.
Side effects: Nausea, vomiting, major flushing of
skin, eye redness, headache, and rash
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BecausealkylationisanormalreactionthattakesplaceintheDNAbetween
chemicalcompounds,theseagentsareabletobindtocertainbasesofthe
DNA.
Sideeffectsmayincludelowbloodcounts,nausea,vomiting,mouthsores,
hairloss,darkeningofveinsusedforinfusion,andlossoffertility.
Nitrosoureascrosstheblood-brainbarrierthatsurroundsthecentral
nervoussystem.Becauseofthisability,theycanbeusedtotreatcancersin
thebrain.
Cyclophosphamideisanitrogenmustard.
Mitoticinhibitorspreventmitosisatthemetaphasestage.Mitosisisthe
processofcelldivisionthatallcellsmustperform.Agroupofalkaloids
derivedfromplantsareusedtopreventthiscellularreproduction.
Theinflammationassociatedwiththedevelopmentoflymphomasoften
leadstoenlargementofthelymphnodes,whichcanbeanearlysymptomof
thecancer.
• Althoughthesignsandsymptomsofthesetwoformsoflymphomaoverlap,
theyaretreateddifferentlyandhavedifferentprognoses.
• StandardcombinationssuchasMOPPorABVDtherapy,forexample,canbe
usedforthetreatmentofHodgkindisease.
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Lymphomas
⬤ Cancers
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of the lymphatic system
Develop in lymph nodes or spleen
⬤ Risk
factors: Immunodeficiency disorders, and
exposure to herbicides/pesticides
⬤ Two categories: Hodgkin's and non-Hodgkin's
⬤ Treatment: Prevention, aggressive treatment
of infection, and radiation therapy
⬤ Drug treatment: Chemotherapeutic agents
(vary depending on type and stage of cancer)
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Bleeding Disorders
⬤ Hemophilia:
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Intermittent bleeding episodes
Associated with either a deficiency or lack of either
antihemophilic Factor VIII or Factor IX
⬤ Von
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Willebrand’s disease
Lack of platelet binding to vasculature
⬤ Both
are defects in the clotting or coagulation
process
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Bleedingdisordersgenerallyareassociatedwithadefectinoneormore
clottingfactorsinvolvedinthecoagulationprocess.
TreatmentinvolvesstrategiestoincreasetheavailabilityofvonWillebrand’s
factorandincludetheuseofcryoprecipitate,FactorVIIIconcentrates,
desmopressin(DDAVP),freshfrozenplasma,andestrogentherapy.
DDAVPisavailableforIV,subcutaneous,oral,andintranasaladministration.
DDAVPisindicatedforbleedingprophylaxisandforthetreatmentof
hemophiliaA,hemorrhage,surgicalbleeding,andvonWillebranddisease.
Extremecareshouldbetakenwhenpreparingwarfarinprescriptionsto
ensurethatthepatientisreceivingthecorrectdosageandinstructionsfor
use.Thepharmacistshouldadditionallyensurethatthosetakingwarfarin
understandthattheyshouldavoidtakingaspirinandotherNSAIDsbecause
oftheriskofbleeding.Thesepatientsshouldalsobeconsistentintheir
intakeoffoodsrichinvitaminKsuchasspinachandliverbecauseofthe
potentialforthesefoodstoaffecttheanticoagulanteffectofwarfarin.