Download - Obat Antianemia
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OBAT ANTIANEMIA
EVI SOVIA
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Anemia: penurunan konsentrasi seldarah merah atau hemoglobin
Kriteria anemia: Wanita: b ! "# g$dl atau hematokrit !
%&'
(aki)laki:b ! "* g$dl atau hematokrit !*+'
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Anemia
#ndmost presenting mani,estation o,disease- .ith pain being the /rst0
It is de/ned as: lo. hemoglobin- lo. 1B23ount and lo. 1B2 mass0
4suall5 presents .ith pallor- ,atigabilit5-.eakness and pale 3on6un3ti7ae
In order to properl5 treat the anemia- 5oumust determine the 3ause0
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2auses o, Anemia
"0 8iminished produ3tion and orrepla3ement o, red blood 3ells0
#0 E93essi7e breakdo.n and loss o,red blood 3ells0
emodilution .hile not a 3ause o,anemia- it does 3ause an anemia)like
ee3t0
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"0 8iminished ;rodu3tion$1epla3emento, 1B2 de/3ien35 o, ?e 1B2 de/3ien35 o,Er5thropoietin
2aused b5 3ompromised renal ,un3tion0
Ma3ro35ti3 Anemia) de/3ien35 o, ,oli3 a3idand B"#
8iminished 3ell di7ision and release o, larger 3ellsin 3ir3ulation0
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#0 Breakdo.n o, 1B2
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Obat)obat Antianemia
;iridoksin 4ntuk terapi anemia sideroblastik
idroksiurea 4ntuk terapi si3kle 3ell disease
8e,eroksamin 4ntuk mengkhelat besi pada iron
loading anemia
;rednison 4ntuk anemia hemolitik
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Siklosporin dan antitimosit globulin 4ntuk anemia aplastik
Siklo,os,amid dosis tinggi dan iradiasi
seluruh tubuh 4ntuk anemia aplastik- sindroma
mielodisplastik- talasemia dan anemiasel sabit
Besi 4ntuk anemia hipokrom mikrositer 5ang
berhubungan dengan de/siensi besi
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Vitamin B"# dan ,olat 4ntuk anemia megaloblastik
Eritropoietin 4ntuk anemia pada pen5akit gin6al
stadium akhir dan anemia 5angberhubungan dengan kanker tertentu
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Besi ?e
8iberikan se3ara peroral atauparenteral pada kasus 5ang berat
;emberian preparat besi Cmeningkatkan ke3epatan produksisel darah merah sesuai dengan
6umlah besi 5ang tersedia dalam sel
eritroid sumsum tulang
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Iron 253le
D ) "+'o, ingested
iron is absorbed
On3e ingested thea3idin the stoma3h:
"0 Aids inioniation o, iron #0 Splits 3helated
,ood iron,rom3helator
%0 Maintains iron
in soluble ,orm *0 Allo.s iron to
remain in theabsorbable ,orm?e%F
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Me3hanism o, Iron Absorption
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Therapeuti3 uses o, Iron
Iron 8e/3ientAnemia
;regnan35
;remature Babies
Blood loss
ook.ornin,estation
MalabsorptionS5ndrome
@I Bleeding due to: 4l3ers Aspirin
E93ess 3onsumptiono, 3oee
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Iron ;reparations
Oral Iron
?errous Sul,ate?eosol > %++ mg tid Side Ee3ts are e9tremel5 mild:
Nausea- upper abdominal pain- 3onstipation ordiarrhea0
2heapest,orm o, Iron and one o, the most.idel5 used
;arenteral Iron 8e9tranIm,eron > IM or IV
Indi3ated ,or patients .ho 3annot tolerate orabsorboral ironor .here oral iron isinsuG3ient to treat the 3ondition ie0Malabsorption s5ndrome- prolonged sali35late
therap5- dial5sis patients
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;emberian at besi C produksi seldarah merah H
1OA: p0o atau parenteral
Absorpsi meningkat bila diberikanbersama as3orbate mereduksi besidari bentuk ,erri men6adi ,erro
8istribusi: plasma trans,erin proteinglikoprotein
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O7erdosis ?e C muntah- gastritishemoragik- hipotensi- letargi
Terapi C gastrik la7age dengansodium bi3arbonat dan pemberiande,eroksamin
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To9i3it5 o, Iron O7erdose
D+++ deaths$5earin the 4S- usuall5 in3hildren
#+' o, 3hildren presenting .ith ironto9i3it5 .ill die
" to # grams are suG3ient to 3ause death
At high doses- Iron is absorbed throughpassi7e diusion .ith no regulation
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Iron > 2lini3al Ee3ts
Earl5 3hanges Vomiting- diarrhea Blood Volume 1 T;1ree9
A3idosis ,rom Iron o9idation- Krebs 353le and
anaerobi3 metabolism 3itri3 a3id and la3ti3
a3id
Intermediate 3hanges Impro7ement short li7ed pro,ound sho3k
and 2V 2ollapse epati3 ?ailure- 6aundi3e-pulmonar5 edema and death
(ate Stage Intestinal s3arring- ,att5 a3id degeneration o,
li7er- 3irrhosis and death0
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Treatment o, Iron O7erdose
To9i3 le7els A(8 > #++)%++mgkg- plasma iron J %++ug$dl
AB2
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Vitamin B"# ada dalam # bentukkoenim: M2B metil B"# dandeoksiadenosilkobalamin
deoksiadenosil B"#
M2B
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Vitamin B"# Absorpsi: memerlukan ,aktor intrinsik
glikoprotein 5ang dihasilkan oleh sel
parietal Anemia pernisiosa C ,ungsi sel parietal
)
8istribusi: terikat dengan plasma
globulin kemudian ditranspor ke6aringan terutama hati dan disimpansebagai koenim
Siklus enterohepatik C
mempertahankan konsentrasi 7it B"#
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Vitamin B"#
Sour3e: In ,ood- espe3iall5 in li7er andkidne5s0 @I Mi3roorganism s5nthesis- VitaminSupplements 25ano3obalamin
Ne3essar5 ,or normal 8NA s5nthesis
Absorption o, B"#
"0 Intrinsi3 ?a3tor lo. dose: a protein made b5stoma3h parietal 3ells that binds to B"# and deli7ers it,rom the ileum 7ia a 3al3ium mediated e7ent0
#0 Mass A3tion igh dose: "+++mg$da5- absorbed7ia passi7e diusion
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B"#8e/3ien35
A B"#de/3ien35.ill 3ause peripheral
neuropath5 and a ma3ro35ti3 anemia- aperni3ious anemia0
?oli3 A3idadministration 3an 3orre3t thema3ro35ti3 anemia but .ill ,ail to 3orre3tthe peripheral neuropath50
To treat the neuropath5- Vit B"#must be
utilied0
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Therapeuti3 4ses o, B"# 8ail5 1eLuirements ) +0)"0+ mh$da5 T
"$#
"5ear
;erni3ious Anemia
Impaired @I absorption o, B"#
@astre3tom5
2orrosi7e In6ur5o, @I mu3osa
?ish tape .orm: .orm siphons o B"#
;la3ebo abuse .ith B"#- espe3iall5 in elderl5
patients0
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Asam ,olat 8alam makanan: pol5glutamat
8ihidrolisis oleh karboksipeptidase-
direduksi men6adi dihidro,olat reduktasedidalam intestin
8imetilasi men6adi MT? methen5l
tetrah5dro,olate kemudian ditransportke 6aringan
Siklus enterohepatik
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?oli3 A3id
Sour3e in ,ood > 5east- egg 5olk- li7er and lea,57egetables
?oli3 A3id ?0A0 is absorbed in the smallintestines0
?0A0 is 3on7erted to tetrah5dro,olate b5dih5dro,olate redu3tase0
?oli3 A3id de/3ien35 ?0A0 8e/3ien35 is also 3alledWill
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Therapeuti3 4ses o, ?oli3 A3id
"0 Megaloblasti3 Anemiadue toinadeLuate dietar5 intake o, ,oli3 a3id
2an be due to 3hroni3 al3oholism- pregnan35-in,an35- impaired utiliation: uremia- 3an3er orhepati3 disease0
#0 To alle7iate anemiathat is asso3iated.ith dih5dro,olate redu3tase inhibitors0
i0e0 Methotre9ate2an3er 3hemotherap5-;5rimethamineAntimalarial
Administration o, 3itro7orum ,a3tormeth5lated
,oli3 a3id alle7iates the anemia0
Therapeuti3 4ses o, ?oli3 A3id
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Therapeuti3 4ses o, ?oli3 A3id3ont
%0 Ingestion o, drugs that inter,ere .ithintestinalabsorptionand storage o, ,oli3 a3id0
Me3hanism) inhibition o, the 3on6ugases that breako ,oli3 a3id ,rom its ,ood 3helators0
E90 > phen5toin- progestin$estrogens oral3ontra3epti7es
*0 Malabsorption > Sprue- 2elia3 disease-
partial gastre3tom50
D0 1heumatoid arthritis> in3reased ,oli3 a3iddemand or utiliation0
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;iridoksin Vitamin B
8igunakan untuk anemiasideroblastik ditandai dengan inti seldarah merah 5ang mengandung
partikel besi C de/siensi sintesis bdan akumulasi besi dalammitokondria sel prekursor eritroid
5ang disebut 3in3in sideroblast Sel terdiri dari S8M normal dan sel
hipokrom dan mikrositer
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;iridoksin C memperbaiki de/siensisintesis asam 5ang diperlukan untuksintesis hemoglobin
;iridoksin terdapat dalam makanan
8iabsorpsi dengan baik padapemberian peroral
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Eritropoietin
Beberapa ,aktor humoral dan selulerberperan dalam eritropoiesis- 5angpaling berperan adalah eritropoietin
Eritropoietin C merangsangproli,erasi- di,erensiasi- dan maturasistem sel men6adi sel hematopoietik
P+' erotropoietin disintesis dalamkortek gin6al dan sisan5a diekstrarenal terutama sel hati
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ipoksia C sekresi eritropoietin H
Anemia- hipobaria- iskemia C 1B? QC produksi eritropoietin H
8iberikan IV atau S2
T"$# R 6am Konsentrasi pun3ak di3apai dalam )
"# 6am setelah pemberian S2
8istribusi ke seluruh tubuh Metabolisme di hepar
Sites o, a3tion ,or E;O
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Sites o, a3tion ,or E;O
Bi l i l A ti , Oth
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Biologi3al A3tions o, Otherematopoieti3 @ro.th ?a3tors
"0 @ranulo35te$Ma3rophage 2olon5 Stimulating?a3tor @M)2S?) Sargramostim A3ts s5nergisti3all5 .ith I()% to stimulate the
,ormation and proli,eration o, 3olon5 ,orming 3ells:2?4)@EMM- B?4)E- 2?4)Meg- 2?4)@M- 2?4)M- 2?4)E
In3reases 35toto9i3 phago35ti3 a3ti7it5o, maturegranulo35tes
#0 Interleukin % I()% A3ts s5nergisti3all5 .ith @M)2S?to stimulate the
,ormation o, granulo35tes- ma3rophages- eosinophilsand megakar5o35tes0 A3ts s5nergisti3all5 .ith E;Oto stimulate ,ormation
o, B?4)E3olonies Indu3es 2?4)S and leukemi3 blast 3ells into 3ell 353le
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More ematopoieti3 @ro.th?a3tors
%0 2olon5 stimulating ?a3tor)" 2S?)" or M)2S?
A3ts s5nergisti3all5 .ith @M)2S? and I()% to
stimulate mono35te$ma3rophage 3olon5,ormation and ,un3tion
*0 @ranulo35te 2olon5 Stimulating ?a3tor
@)2S? ) flgrastim A3ts s5nergisti3all5.ithI()%- @M)2S? and 2S?)"tostimulate ,ormation o, megakar5o35tes- granulo35te)ma3rophage and high proli,erati7e potential ;;3olonies
Indu3es release o, granulo35tes ,rom marro.
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More ematopoieti3 @ro.th?a3tors
D0 Thrombopoietin TS? In3reases the sie and number o, megakar5o35tes0
I()"" also use,ul in stimulating produ3tion
In3reases the 3on3entration o, earl5 megakar5o35tes3ellsSA2EF3ells in bone marro.0
;rodu3es an in3rease in megakar5o35tesendomitosis0
In3reases platelet sie and number in plasma0
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idroksiurea
8igunakan untuk terapi anemia selsabit- dimana ter6adi peningkatansintesis ,etal b
Mekanisme ker6a belum 6elas- tetapimempengaruhi ribonukleotidadi,os,at reduktase C tahap
biosintesis 8NA C menghan3urkanpembentukan radikal bebas tirosildalam pusat katalitik enim
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Absorpsi peroral baik
Konsentrasi pun3ak di3apai dalam #6am
ESO: menekan hematopoietik-neutropenia
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8e,eroksamin
8e,eroksamin e,ekti, mengikat besiC digunakan untuk anemia dengankelebihan besi
A/nitas tinggi terhadap ion besi danmengikat besi dari hemosiderin dan,eritin- 6uga dari trans,erin
8e,eroksamin tidak mengikat besipada b
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Absorpsi peroral buruk
T"$# "D menit
8iberikan melalui S2 pump
ESO: reaksi alergi- neurotoksik padapenggunaan 6angka pan6ang
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Imunosupresan
Siklosporin dan antitimosit globulindigunakan untuk anemia aplastik
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Antitimosit globulin
8iberikan se3ara IV setelahdilarutkan dalam salin normal dandiberikan melalui in,us pada kateter
intra7ena sentral ESO: ana/laksis- serum si3kness
k ki ik
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?armakokinetik
Drug
s
RO
A
Notes
Recombinant
humanerythrop
oietin
IV,SC
SCmaybe as
effective asIV,!"# $
hr
Iron Ora%,I&,I
Absorpsi p'oferrou
? k ki ik
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?armakokinetik
Dru
gs
RO
A
Notes
Asamfo%at
Ora%,I&,
IV
Absorpsi p'ogoo(,
enterohepaticcyc%in
g
Vitamin*!#
Ora%,SC,I&
Ora%routeineffective in
? k ki ik
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?armakokinetik
Dru
gs
R
OA
Notes
-i(rosi
urea
Ora%
Absorpsi p'o
goo(
+re(nison
Ora%orIV
Absorpsi p'ogoo(
Si%
osp
Or
a%
Ora%
(ose is
? k ki tik
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?armakokinetik
Drugs RO
A
Notes
Deferosamin
SCorIV
Absorpsip'opoor,mustbegivenbycontin