Farmakologi Sistem Hematologi

5/23/2018 Farmakologi Sistem Hematologi

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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 !padaumumn)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/ whichtogether with glo-in chains ,orms hemoglo-in !inti cincin hemeiron+porph)rin )ang -ersama+sama rantai glo-in mem-entukhemoglo-in$

H- : -inds o*)gen 2 pro1ides the critical mechanism ,or o*)gendeli1er) ,rom lugs to other tissues !mengikat oksigen danmengedarkan 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 menstruati

woman !A-sor-si total 0at -esi meningkat &+' mg pada wan

menstruasi.

Absorbsi Pada Remaja ron content !mg$

Men 9omen

Hemoglo-in 656 &66

M)oglo-in

Transport !trans,errin$ > ?

Storage !,erritin 2 other ,orms$ 56 66

Total


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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 mekanismepengeluaran 0at -esi$

Small amounts are lost -) e*,oliation o, M@ into the stool

Trace amounts are e*creted in -ile/ urine/ and sweat !melaluiempedu/ urin/ dan keringat$

8o more than 1 mgo, iron lost per da) !Tidak le-ih dari & mgperhari$

CLINICAL PHARMACOLOGY

The onl) clinical indication : treatment or pre1ention o, ironde(cienc) anemia !ndikasi : engo-atan atau mencegah anemiade,. -esi$

ron de(cienc) can -e ,ound in : in,ants !premature in,ants$/ rapidgrowth period/ pregnant/ lactating woman/ post gastrectom)/patient with se1ere small -owel disease that result in generali0edmala-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


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PHARMACOKINETICS O2 +ITAMIN ./0

Once a-sor-ed/ %it #&' is -ound to transco-alamin andtransported to 1arious cells o, the -od) !Saat doa-sor-si/ %it.&'terikat dengan Transco-alamin $

A1erage diet !USA$ ontain 345 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 useD ,or pernicious anemia 2 anemia caused -) gastric resection

2OLIC ACI-

@o,actor ,or trans,er reaction o, one car-on la) 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

,etus !spina -i(da$ FA de(cienc) associated with : @ancer/ leukemic/ m)eloproli,erati1disorders/ certain chronic skin disease/

4rugs that can inter,ere the a-sorption 2 meta-olism o, FA : hen)toin !A-s$ Some anticon1ulsant !A-s$ Oral contracepti1es !A-s$ sonia0id !A-s$ Methotre*ate Trimethoprim 2 )rimethamine !inhi-it deh)dro,ola

reductase$

PHARMACO-YNAMIC

@on1erted to tetrah)dro,olate -) deh)dro,olate reductase


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harmacolog) o, Hemostatic 4rug 2 Anti

@oagulant

REG:LATION O2 COAG:LATION 1 2I.RINOLYSIS

The central process o, (-rinol)sis : con1ersion o, inacti1e plasminogento the proteol)tic en0)me plasmin

MECHANISM O2 .LOO- COAG:LATION

#lood coagulates -) the trans,ormation o, solu-le (-rinogen intoinsolu-le (-rin

Se1eral circulating protein interact in a cascading series o, limitedproteol)tic reactions

A clotting ,c 0)mogen !,c %$ limited proteol)sis an acti1eprotease !,c %a$

=ach protease acti1ates the ne*t clotting ,c solid (-rin clot,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

a$ rothrom-in is -ound -) @a to a platelet phospolipid !$ sur,ac

where acti1ated ,c J !Ja$/ in the presence o, ,c %a/ con1ert it incirculating 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 acti1at

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

(-rin/ 2 acti1ates ,c J/ an insolu-le/ cross+linked (-molecule


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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

!aTT$ eak therapeutic le1el !M9 heparin$: 6/5 & 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 urpura 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 enal disease

A-MINISTRATION 1 -OSAGE

&. To pre1ent pulmonar) em-oli in atient with esta-lished 1enothrom-osis : 6/' 6/< unitDm !protamine titration$ aTT should -e controlled in ? hours a,ter admintrs

'. roph)lactic !eno*aparin$ : 6 mg twice dail) or


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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' eNuire -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 lasma Fraction Fi-rinol)tic nhi-itors !Aminocaproic acid$ Serine rotease nhi-itors !Aprotinin$

Anti Fi-rinol)tic 4rug

CONSIST O2 =+ Streptokinase+ Urokinase+ Tissue plasminogen acti1ator+ Alteplase

+ eteplase apidl) l)sis throm-in -) catal)sing the ,ormation o, the serin

protease plasmin ,rom its precursor 0)mogen/ plasminogen

STREPTOKINASE

rotein s)nthesi0ed -) streptococci/ com-ines with proacti1atplasminogen

@atal)0es the con1ersion o, inacti1e plasminogen to acti1e plasm

:ROKINASE human en0)me s)ntesi0e -) the kidne)

IN-ICATION

Multiple pulmonar) em-oli @entral deep 1enous throm-osis Acute m)ocardial in,arction eripheral 1ascular disease

-OSAGE

Stre!to>inase4 : '56.666 units !%$/ ,ollowed -) &66.666 units ,or 'inase4 : 66.666 units !&6 minutes$/M4 : 66.666 units ,or &' hours

Documents

Farmakologi Sistem Hematologi