Farmakologi Sistem Hematologi

Oleh: dr. Sakura Tola

Agents Used in Anemias; Hematopoietic Growth
Factor
HEMATOPOIESIS
Memerlukan tiga kompenen nutrisi:
ron !"at #esi$
%itamin #&'
Folic acid
Anemia : de(cienc) in o*)gen carr)ing+er)throcite
IRON
ron de(cienc) : the most common cause o, chronic anemia !pada
umumn)a dise-a-kan oleh anemia kronik$
.eads to : pallor!pucat$/ ,atigue!lemah$/ di00iness!1ertigo$/
e*ertional d)spnea!sesak$/ etc
Forms : the nucleus o, the iron+porph)rin heme ring/ which
together with glo-in chains ,orms hemoglo-in !inti cincin heme
iron+porph)rin )ang -ersama+sama rantai glo-in mem-entuk
hemoglo-in$
H- : -inds o*)gen 2 pro1ides the critical mechanism ,or o*)gen
deli1er) ,rom lugs to other tissues !mengikat oksigen dan
mengedarkan dari paru+paru ke 3aringan lain.$
PHARMACOKINETICS
A-sorption
A-sor-ed in duodenum/ pro*imal 3e3unum !4ia-sor-si di duodenum
dan -agian proksimal 3e3enum$
A normal indi1idual !without iron de(cienc)$ a-sor-s 5+&67 !6/5+&
mg dail)$ o, iron !8ormaln)a/ manusia menga-sor-si 0at -esi 5+
&67 !6/5+& mg perhari$$ ; a1erage diet in USA !&6+&5 mg dail)$
Total iron a-sorption increase to &+' mg in normal menstruating
woman !A-sor-si total 0at -esi meningkat &+' mg pada wanita
menstruasi.
Absorbsi Pada Remaja ron content !mg$
Men 9omen
Hemoglo-in :656 &;66
M)oglo-in <:6 :66
=n0)mes &6 >
Transport !trans,errin$ > ?
Storage !,erritin 2 other ,orms$ ;56 :66
Total <'<> ':&<
A1aila-le a-undant in meat !terdapat dalam dagin$
A-sorption is decreased -) the presence o, chelators or comple*ing
agents in intestine lumen !A-sor-si menurun 3ika terdapat chelator
or comple*ing agents dalam lumen usus$
A-sorption increased in the presence o, h)drochloric acid 2 1itamin
@ !Meningkat dengan h)drochloric acid 2 1it. @$
TRANSPORT
ron is transported in the plasma -ound to trans,erring !"at -esi
ditranspor dalam plasma$
@rosses the intestinal mucosal cell -) acti1e transport !menem-us
mukosa usus dengan -) acti1e transport$
ncreased er)thropoiesis is associated with an increase the num-er
o, trans,errin receptors
STORAGE
#inds a1idl) to a protein apoferritin, ,orms comple* ferritin
t is stored in intestinal mucosal cell/ macrophages in the li1er/
spleen/ -one
Apo,erritin s)nthesis is regulated -) the le1els o, ,ree iron
ELIMINATION
8o mechanism ,or e*cretion o, iron !Tidak ada mekanisme
pengeluaran 0at -esi$
Small amounts are lost -) e*,oliation o, M@ into the stool
Trace amounts are e*creted in -ile/ urine/ and sweat !melalui
empedu/ urin/ dan keringat$
8o more than 1 mg o, iron lost per da) !Tidak le-ih dari & mg
perhari$
CLINICAL PHARMACOLOGY
The onl) clinical indication : treatment or pre1ention o, iron
de(cienc) anemia !ndikasi : Aengo-atan atau mencegah anemia
de,. -esi$
ron de(cienc) can -e ,ound in : in,ants !premature in,ants$/ rapid
growth period/ pregnant/ lactating woman/ post gastrectom)/
patient with se1ere small -owel disease that result in generali0ed
mala-sorption !4e,. "at -esi -iasa ditemukan : -a)i premature/
pertum-uhan cepat/ #umil/ 9anita men)usui/ pasien dengan small
-owel dis )ang -erat )ang mengaki-atkan mala-sor-si$
ron de(cienc) is diagnosed : !la-orator) measurement$
Serum iron B <6 CgDdl
T#@ E <66 CgDdl
ron -inding saturation B &6 7
Serum ,erritin B &6 CgD.
Ta-el &. Some @ommonl) used oral iron preparation
Areparation Ta-let si0e
=lemental iron
per ta-let
Usual adult
dosage ta-let per
da)
Ferrous sul,ate/
h)drated
:'5 mg ?5 mg : + <
Ferrous sul,ate/
desiccated
'66 mg ?5 mg : + <
Ferrous gluconate :'5 mg :? mg : + <
Ferrous ,umarate '66 mg ?? mg : + <
Ferrous ,umarate :'5 mg &6? mg ' + :
TREATMENT
&. Oral iron therap)
'. Aarenteral iron therap)
ndication :
%arious postgastrectom) condition
Are1ious small -owel resection
nFammator) -owel disease
Mala-sorption s)ndrome
@onsist o, : iron dextran (om!"ex o# #erri $%droxide&'
iron(s)rose om!"ex' iron sodi)m *")onate om!"ex
(dee! IM' I+ in#)sion&
4osage ,or iron de*tran : '6 G <6 ml !%$
CLINICAL TO,ICITY
A)te iron toxiit%
8ecroti0ing gastroenteritis !1omiting/ a-dominal pain/ -lood)
diarrhea ,ollowed -) shock/ letharg)/ d)spnea$
Should -e gi1en -e#eroxamine
C$roni iron toxiit%
Hemochromatosis
HD Ahle-otom)
+ITAMIN ./0
@o,actor !Merupakan Io,aktor$
4e(cienc) leads to anemia/ gastrointestinal s)mptoms/ neurologic
a-normalities !de,. menim-ulkan anemia/ ge3. Gastrointestinal dan
a-normalitas neurologic$
@onsist o, a porph)rin+like ring with a central co-alt atom !T.4.
porph)rin )ang men)erupai cincin dengan atom co-alt di
tengahn)a$
C%anooba"amin 1 $%droxooba"amin
PHARMACOKINETICS O2 +ITAMIN ./0
Once a-sor-ed/ %it #&' is -ound to transco-alamin and
transported to 1arious cells o, the -od) !Saat doa-sor-si/ %it.&'
terikat dengan Transco-alamin $
A1erage diet !USA$ ontain 3(45 6* o# 7it ./0 dai"%8 /(3 6* o#
9$i$ is absorbed
PHARMACO-YNAMICS O2 +IT ./0
@o,actor ,or se1eral reaction in the -od) :
@on1ersion o, the ma3or dietar) and storage ,olate to
tetrah)dro,olate
someri0ation o, met$%"ma"on%"(CoA to a7oid ne)ro"o*i
disorder
@linical use
HD ,or pernicious anemia 2 anemia caused -) gastric resection
2OLIC ACI-
@o,actor ,or trans,er reaction o, one car-on
Ala) a role in normal 48A s)nthesis !#erperan dalam sintesis 48A$
4e(cienc) : megalo-lastic anemia
4e(cienc) in pregnanc) : increase risk o, neural tu-e de,ects in
,etus !spina -i(da$
FA de(cienc) associated with : @ancer/ leukemic/ m)eloproli,erati1e
disorders/ certain chronic skin disease/
4rugs that can inter,ere the a-sorption 2 meta-olism o, FA :
Ahen)toin !A-s$
Some anticon1ulsant !A-s$
Oral contracepti1es !A-s$
sonia0id !A-s$
Methotre*ate
Trimethoprim 2 A)rimethamine !inhi-it deh)dro,olate
reductase$
PHARMACO-YNAMIC
@on1erted to tetrah)dro,olate -) deh)dro,olate reductase
Aharmacolog) o, Hemostatic 4rug 2 Anti
@oagulant
REG:LATION O2 COAG:LATION 1 2I.RINOLYSIS
The central process o, (-rinol)sis : con1ersion o, inacti1e plasminogen
to the proteol)tic en0)me plasmin
MECHANISM O2 .LOO- COAG:LATION
#lood coagulates -) the trans,ormation o, solu-le (-rinogen into
insolu-le (-rin
Se1eral circulating protein interact in a cascading series o, limited
proteol)tic reactions
A clotting ,c 0)mogen !,c %$ limited proteol)sis an acti1e
protease !,c %a$
=ach protease acti1ates the ne*t clotting ,c solid (-rin clot is
,ormed
Fi-rinogen !,c $ is the su-strat ,or the en0)me throm-in !,c a$
The en0)me throm-in is ,ormed -) acti1ation o, prothrom-in !,c
a$
Arothrom-in is -ound -) @a to a platelet phospolipid !A.$ sur,ace/
where acti1ated ,c J !Ja$/ in the presence o, ,c %a/ con1ert it into
circulating throm-in
The main initiator o, -lood coaglt : tissue ,c !TF$D,c %a pathwa).
The e*posure o, TF on damaged endothelium -inds 2 acti1ates
circulating ,c %
This comple*/ in turn acti1ates ,c J 2 J
Throm-in/ in turn/ acti1ates upstream proteins/ primaril) ,c %/ %/
2 J
Throm-in : a potent acti1ator o, platelets/ con1erts (-rinogen to
(-rin/ 2 acti1ates ,c J/ an insolu-le/ cross+linked (-rin
molecule
IN-IRECT THROM.IN INHI.ITORS
HEPARIN
A heterogeneous mi*ture o, sul,ated mucopol)saccharides
@atal)0es the antithrom-in+protease reaction
@onsist o, :
Un,ractioned heparin !UFH$
.ow+molecular+weight heparin !.M9H$ !Enoxa!arin'
-a"te!arin' Tin;a!arin$
TO,ICITY
The ma3or S= : -leeding
S= can -e decreased -) :
Scrupulous patient selection
@are,ull control o, dosage
@lose monitoring o, the acti1ated partial throm-oplastin time
!aATT$
Aeak therapeutic le1el !.M9 heparin$: 6/5 G & unitDm./ twice
dail) dosing; determined < hours a,ter administration
CONTRAIN-ICATION HEPARIN
H)persensiti1e to the drug
Acti1el) -leeding
Hemophilia
Signi(cant throm-oc)topenia
Aurpura
Se1ere h)pertension
ntracranial hemorrhage
n,ecti1e endocarditis
Acti1e tu-erculosis
Ulcerati1e lesion o, the G tract
Threatened a-ortion
%isceral carcinoma
Ad1anced hepatic disease
Henal disease
A-MINISTRATION 1 -OSAGE
&. To pre1ent pulmonar) em-oli in Aatient with esta-lished 1enous
throm-osis :
6/' G 6/< unitDm. !protamine titration$
aATT should -e controlled in ? hours a,ter admintrs
'. Aroph)lactic !eno*aparin$ : :6 mg twice dail) or <6 mg once dail)
!sc$
:. Aroph)lactic !dalteparin$ : 5666 unit !sc$ once dail)
<. %enous disease : '66 unitsDkg once dail)
5. Acute coronar) s)ndrome : &'6 unitsDkgD&' hours
-IRECT THROM.IN INHI.ITORS
8ew class o, agents
=*ert the anticoagulant eKect -) directl) -inding to the acti1e site
o, throm-in/ there-) inhi-iting throm-inLs downstream eKects
8o additional -inding protein
4o not -ind to other plasma protein !platelet ,actor <$
@onsist o, :
Hirudin/ #i1alirudin !-ind at -oth the catal)tic 2 acti1e site o,
trhom-in$
Argatro-an/ Melagatran !onl) at throm-in acti1e site$
<AR2ARIN 1 THE CO:MARIN ANTICOAG:LANT
Administered as the sodium salt
Has &667 -ioa1aila-ilit)
A-out MM7 is -ound to plasma al-umin
Hal,+li,e in plasma : :? hours
The lack o, urinar) e*cretion o, unchanged drug
MECHANISM O2 ACTION
@oumarin anticoagulant -lock the +car-o*)lation o, se1eral
glutamate residues in prothrom-in 2 ,actors %/ J/ 2 J
The protein car-o*)lation coupled with the o*idati1e deacti1ation
o, 1it I
Are1ent reducti1e meta-olism o, inacti1e 1it I epo*ide -ack to its
acti1e h)droNuinone ,orm
TO,ICITY
@rosses the placenta +E hemorrhagic disorder in ,etus 2
a-normal -one ,ormation
@utaneus necrosis !in the &st week o, therap)$
Frank in,arction o, -reast/ ,att) tissue/ intestine/ 2 e*tremities
!rarel)$
-R:G INTERACTION
4rugs Used n #leeding 4isorders
+ITAMIN K
Fat+solu-le su-stance
Found primaril) in lea,) green 1egeta-les
Additionall) s)nthesi0ed -) -acteria in human intestine
A1aila-le in ' ,orms : %it I& 2 %it I'
HeNuire -ile salt ,or a-sorption
A1aila-le in ta-let 5 mg 2 ampules 56 mg
The eKect is complete in '< hours
% : should -e slowl) -+co0 rapid in,usion can produce d)spnea/
chest 2 -ack pain/ death
Alasma Fraction
Fi-rinol)tic nhi-itors !Aminocaproic acid$
Serine Arotease nhi-itors !Aprotinin$
Anti Fi-rinol)tic 4rug
CONSIST O2 =
+ Streptokinase
+ Urokinase
+ Tissue plasminogen acti1ator
+ Alteplase
+ Heteplase
Hapidl) l)sis throm-in -) catal)sing the ,ormation o, the serine
protease plasmin ,rom its precursor 0)mogen/ plasminogen
STREPTOKINASE
Arotein s)nthesi0ed -) streptococci/ com-ines with proacti1ator
plasminogen
@atal)0es the con1ersion o, inacti1e plasminogen to acti1e plasmin
:ROKINASE
human en0)me s)ntesi0e -) the kidne)
IN-ICATION
Multiple pulmonar) em-oli
@entral deep 1enous throm-osis
Acute m)ocardial in,arction
Aeripheral 1ascular disease
-OSAGE
Stre!to>inase
.4 : '56.666 units !%$/ ,ollowed -) &66.666 units ,or '<+;'
hours
:ro>inase
.4 : :66.666 units !&6 minutes$/
M4 : :66.666 units ,or &' hours