k-9 drugs used for anemia

8/21/2019 K-9 Drugs Used for Anemia

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Drugs Used for

Anemia

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Hematopoiesis

The production from undierentiatedstem cells of circulating erythrocytes,

platelets, and lukocytes, is aremarkable process that produces

over 200 billion new cells per day inthe normal person and even greater

numbers of blood cells in people withconditions that cause loss or

destruction of blood cells

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The hematopoietic machinery: resides primarily in the bone marrow in

adults

!e"uires a constant supply of#

• $ essential nutrients # iron, vit% &12, andfolic acid

• 'ematopoietic growth factors

()protein that regulate the proliferationand dierentiation of hematopoietic cells*

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Iron

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+ronorphyrin heme ring - .lobinchain

'emoglobin

'b reversibly binds /2

eciency iron) icrocytic hypochromicanemia



+ron istributon in 3ormal4dults

Iron Content (mg)

en Women

'emoglobin $050 1600

yoglobin 7$0 $00

8n9ymes 10 :

Transport (transferrin* : ;

<torage (ferritin and otherforms*

650 $00

Total 727: 2$17

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4bsorption

• 3ormally absorbed in the duodenumand pro=imal >e>unum, though themore distal samll intestine can absorb

iron if necessary• 'eme iron in meat hb and myoglobin

can be absorb intact

• +ron in vegetables and grains ? tightlybound to phytates or other comple=ingagents ? absorption@@

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3on heme iron in foods and ininorganic iron salt as and

comple=es must be reduces toferrous (Ae2-* iron before it canbe absorbed by the intestinal

mucosal cells

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Oral iron preparations

Preparation Talet si!e(mg)

"lemental ironper talet (mg)

Usual adultdosage (ta

#day)

Aerrous sulfate,

hydrated

$25 ;5 $7

Aerrous sulfate,desiccated

200 ;5 $7

Aerrousgluconate

$25 $; $7

Aerrous fumarate 200 ;; $7

Aerrous fumarate $25 10; 2$

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4dverse eects of oral irontherapy

3ausea, epigastric discomfort, abdominalcramps, constipation and diarrhea

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ose dependent

B the daily dose

Taking the tablet immediatelyafterCwith meals

Dhan in re aration iron salt @@4dr



&lack stools may

obscure the d= ofcontinued

gastrointestinal bloodloss

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arenteral +ron therapy

• Enable to tolerate or absorb oral iron

• 8=tensive chronic blood loss who

cannot be maintained with oral ironalone

• 4long with erythropoietin# oral ironmay not be absorbed at suFcientrate to meet the demands of inducedrapid erythropoiesis

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• The ioni9ed salts of iron used orally,canGt be in>ected because of theirstrong protein precipitating action

• reparation for in>ection#

1%+ron de=tran# colloidal solution# 50mg elemental ironCml

2%+ronsorbitolcitric acid comple=# 50mg ironCml

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arenteral +ron Therapy

+ron deciency anemia#

!e"uire 12 g of replacement iron

/r2070 mH of iron de=tran

(+I , +*

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arenteral +ron Therapy

250 mg Ae untuk setiap gram kekurangan 'b#

ertama 50 mg dilan>utkan 100250 mgsetiap hari atau bbp hari sekali

+I# dosis awal @ 25 mg, ditingkatkan bertahapuntuk 2$ hari sampai tercapai dosis 100mgChr% iberi perlahan 2050 mgCmenit%

7%7Cbb (kg*

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Ad$erse e%ects of parenteraliron therapy

Hocal pain, Tissue staining (browndiscoloration of the tissue overlyingthe in>ection site*, 'eadache, Hight

headedness, Aever, 4rthralgia,3ausea, Iomiting, &ackpain, Jushing,

urticaria, bronchospasm,

anapahyla=is and death (rarely*

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4cute +ron To=icity10 tab? lethal in young

children

3ecroti9ing gastroenteritis, vomiting, abdominal

pain, bloody diarrhea, shock, lethargy, dyspneaetabolic acidosis, com and death

Acti$ated charcoal: doesnot bind iron ? ineective&hole o'el irrigation: to Jush out unabsorbed pillsDeferoamine: a potent ironchelating compound ?

systemically to bind iron that has already been absorbedand to promote its e=cretion in urine and feces



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Dhronic +ron To=icity

('emochromatosis*

8=cess iron deposit in the heart, liver, pancreas,

andother organs ? organ failure and death

Intermittent PhleotomyDeferoamine: eFcient @@@, usefulfor severe iron overload that canGt be

managed by phlebotomy



Aactors facilitating ironabsorption

1% 4cid# by favouring dissolution andrection of ferric iron

2% !educing substances# ascorbic acid,44 containg <' radical% Theseagents reduce ferric iron and formabsorbable comple=es

$% eat# by increasing 'Dl secretionand providing haeme iron

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Aactors impeding ironabsorption

1% 4lkalies(antacids* render ironinsoluble, oppose its reduction

2% Domple=ing iron#

a% hosphates (rich in egg yolk*

b% hytates (in mai9e, wheat*

c% Tetracycline$% resence of other foods in the

stomach

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itamin *+,

• Dofactor for several essentialbiochemical reactions in humans

• eciency of Iit% &12 leads toanemia, gastrointestinal symptoms,and neurologic abnormalities

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Iitamin &12 chemistry

• Donsists of a porphyrinlike ring with acentral cobalt atom attached to anucleotide

• 4ctive forms of the vitamin in human#deo=yadenosylcobalamin andmethylcobalamin

• Dyanocobalamin and hydro=ocobalaminand other cobalamins found in food sourcesare converted to the above active forms

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A- .ethyltransfer

35

ethyltetrahydrofolate

Tetrahydrofolate

ethylcobalamin

Dobalamin

'omocystein

e

ethionine

*- Isomeri!ation of /0.ethylmalonyl0CoA

HethylmalonylDo4

<uccinylDo4

ethylmalonyl

Do4 mutase



1olic Acid



• Iitamin &12 is sometimes callede=trinsic factor to dierentiate it from

intrinsic factor (A+D)protein normallysecreted by the stomach (parietal cell**

• 4bsorbed only after it comple=es withintrinsic factor

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The intrinsic factor0itamin *+,comple

4bsorbed in the distal ileum by a highlyspesic receptormediated transport

system



Dholinergic drugs, histamin, 4DT',corticosteroid, tiroid

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4bsorption of vitamin &12 K

Aactor +ntrinsic Dastle K



osologi

• Tablet #oral

• +n>ection# cyanocobalamin, larutanekstrak hati dalam air, suntikandepot vitamin &12%

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arenteral &12in>ection

• 'ydro=ycobalamin1001000 µg + daily or every other day

for 12 weeks to replenish body store•aintenance # 1001000 µg + once a

month for life• +f neurologic abnormailites are present,

maintenance therapy in>ections should begiven every 12 weeks for ; monthsbefore switching to monthly in>ections



/ral (more e=pensive*doses 1000µg + usually suFcient to

pernicious anemia whorefuse CcanGt tolerate the

in>ections%

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1olic Acid(Pteroylglutamic acid)

• !educed form are re"uired foressential biochemical reaction thatprovide precursors for biosynthesis

of 44, purines and 34%

• A4?'A4?T'A4 by Arase and'A!ase

• eciency) megaloblastic anemia

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T'A4 di b f



T'A4 mediates a number of onecarbon transfer reaction by carrying

amethyl groupas an adduct

1% Donversion of homocysteine tomethionine

2% .eneration of thymidilate, an essential

constiuent of 34$% Donversion of serine to glycine

7% urine synthesis

5% .eneration and utili9ation of formatepool

;% 'istidine metabolism

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Aolic acid deciency

+nade"uate dietary intake, alcoholic,liver disease, pregnant, hemolytic

anemia,

malbsorption,cancer,leukemia,myeloproliferative isorder, renal

dialysis,drugs

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rugs induced folic aciddeciency

• A4 absorption#

henytoin, some otheranticonvulsant, oral contraseptives,+3'

• +nhibit dihydrofolate reductase#

methothre=ate,trimethoprim,primetamne

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Aolic 4cid

1 mg orally daily is suFcient toreverse megaloblastic anemia,restore normal serum folate levels,

and replenish body stores of folates

ose therapeutic# 25 mgCday,prophylactic0%5 mgCday

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4dverse eects

/ral A4 is entirely non to=ic

+n>ections rarely cause sensitivityreactions

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Hematopoietic 2ro'th1actors

• '.A# glycoprotein hormones thatregulate the proliferation anddierentiation of hematopoietic

progenitor cells in the bone marrow• 8rythropoietin (epoitin alfa*,

granulocyte colony stimulating factor

(.D<A*,granulocytemacrophagecolonystimulating factor (.D<A*,and interleukin 1

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8rythropoietin

• 1st human '.A to be isolated, from the urinepatients with severe anemia

• "poitin alfa ) r'u8po (recombinant human

erythropietin*# produced in a mammalian cell e=pression

system using recombinant 34 technology

+I# t1C2 71$ hrs, +E

• Daropoietin alfa: .lycosylated form of erythropoietin

T1C2 2$=LL



4nemia and hypo=ia are sensed by

kidney cells ? rapid secretion of 8/ ?acts on erythroid marrow and#

•

<timulates proliferation of colonyforming cells of the erythroid series

• +nduces '& formation anderythroblast maturation

• !elease reticulocytes in circulation

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8rythropietin# +nternational /lympic comittee

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K !&D ? K /2 delivery? improveperformace



Dlinical Ese

• 4nemia of chronic renal failure

• 4naemia in 4+< patients treated with9idovudine

•Dancer chemotherapy induced anemia

• reoperative increased blood production forautologous transfusion during surgery

• 4nemia due to primary bone marrowdisorders

• 4nemiaassociated with chronic inJammation

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• ost patients can maintain 't $5M

with 8/ 50150 +ECCkg +IC<D$=Cweek

• atients with endogenous

erythropoietin levels#@ 100 +ECH# best chance of response

100500 +ECH# respond occasionally

(150$00 +ECkg $=Cweek*

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4dverse 8ects

• 4ssociated with rapid increased in'ematocrite and 'b, and'ypertension, thrombotic

complication• Alu like symptoms lasting 27 hrs

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k-9 drugs used for anemia

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