Obat Antianemia Warmadewa 2012 Drugs

8/12/2019 Obat Antianemia Warmadewa 2012 Drugs

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Antianemia drugsI Made Jawi

Department ofPharmacology

Faculty of Medicine

Udayana University


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Antianemia drugs

Are therapeutic agents whichincrease either the number of red

cells or the amount of hemoglobin in

the blood


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Types of anemia

Blood loss Inadequate production of blood

Excessive breakdown of blood cells


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Inadequate production of blood

1. Hematopoietic Growth

Factors.

2 Iron insufficiency

3.Vitamine B12 insufficiency4.Folic acid insufficiency


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es o ac on orEPO(Erythropoietin)


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How Erythropoietin Is Taken

(Epoetin alfa, darbepoetin alfa)

Erythropoietin must be injected to be

effective; it can be given intravenously orsubcutaneously.

Erythropoietin works by binding to and

activating specific receptors on the surface of

RBC-producing cells in the bone marrow


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Therapeutic Uses of EPO(erythropoiesis-stimulating agents)

Anemia of end stage renal disease

To treat AIDS anemia caused by AZTssuppression of bone marrow

Anemia related to cancer chemotherapy

Others To increase RBC levels for autologous blood

donation

Anemia associated with rheumatoid arthritis


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Biological Actions of OtherHematopoietic Growth Factors

1. Granulocyte/Macrophage Colony Stimulating Factor(GM-CSF)- Sargramostim

Acts synergistically with IL-3 to stimulate the formation andproliferation of colony forming cells: CFU-GEMM, BFU-E,CFU-Meg, CFU-GM, CFU-M, CFU-E

Increases cytotoxic phagocytic activity of maturegranulocytes

2. Interleukin 3 (IL-3)Acts synergistically with GM-CSF to stimulate the formation

of granulocytes, macrophages, eosinophils andmegakaryocytes.

Acts synergistically with EPO to stimulate formation of BFU-E

colonies Induces CFU-S and leukemic blast cells into cell cycle


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More Hematopoietic GrowthFactors

3. Colony stimulating Factor-1 (CSF-1 or M-

CSF)Acts synergistically with GM-CSF and IL-3 to stimulate

monocyte/macrophage colony formation and function

4. Granulocyte Colony Stimulating Factor

(G-CSF) - filgrastimActs synergistically withIL-3, GM-CSF and CSF-1 to

stimulate formation of megakaryocytes, granulocyte-

macrophage and high proliferative potential (HPP) colonies

Induces release of granulocytes from marrow


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More Hematopoietic Growth

Factors

5. Thrombopoietin (TSF) Increases the size and number of megakaryocytes.

(IL-11 also useful in stimulating production)

Increases the concentration of early megakaryocytes

cells (SACHE+cells) in bone marrow.

Produces an increase in megakaryocytes endomitosis.

Increases platelet size and number in plasma.


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Iron(Fe) Absorption: duodenum and proximal jejunum

Transport: transferrin Storage: ferritin

Excretion: no more than 1 mg per day.


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Iron Cycle

5 - 10% of ingested iron

is absorbed

Once ingested the acidin the stomach:

1. Aids in ionizationof iron

2. Splits chelatedfood iron fromchelator

3. Maintains iron insoluble form

4. Allows iron toremain in theabsorbable form

Fe

3+


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Mechanism of Iron Absorption


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Therapeutic uses of Iron

Iron Deficient

Anemia

Pregnancy

Premature Babies

Blood loss

Hookworn

infestation

Malabsorption

Syndrome

GI Bleeding due to: Ulcers

Aspirin Excess consumption


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Iron Preparations

Oral Iron Ferrous Sulfate (Feosol)300 mg tid

Side Effects are extremely mild: Nausea, upper abdominal pain, constipation or diarrhea.

Cheapest form of Iron and one of the most widelyused

Parenteral Iron Dextran (Imferon)IM or IV

Indicated for patients who cannot tolerate or absorboral iron or where oral iron is insufficient to treat the

condition ie. Malabsorption syndrome, prolongedsalicylate therapy, dialysis patients


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Ferrous Fumarate

Femiron[OTC]; Feostat[OTC]; Ferro-

Sequels[OTC]; Fumasorb[OTC];Fumerin[OTC]; Hemocyte[OTC];

Ircon[OTC]; Nephro-Fer[OTC]; Span-

FF[OTC]


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Toxicity of Iron Overdose

5000 deaths/year in the US, usually in

children 20% of children presenting with iron toxicity

will die

1 to 2 grams are sufficient to cause death

At high doses, Iron is absorbed through

passive diffusion with no regulation


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Treatment of Iron Overdose

Toxic levels ALD200-300mgkg, plasma iron > 300ug/dl

ABCs supportive care

Bicarbonate for acidosis

Fluids for blood loss

Ipecac or lavage

Chelation with Deferoxamine


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Vitamin B12 B12 isessential for cell growth and for

maintenance of normal myelinIt is also important for the normal

metabolic function of folate .


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Absorption and transport of vitaminB12

Vitamin B12binds a glycoprotein (intrinsic factor) in

stomach. I.F. is secreted by the parietal cells.

Vitamin-intrinsic factor complex recognises surface receptors ofmucosal cells in ileum and is absorbed.

It is transported around the body bound to specific a B12binding

protein (transcobalamin).

It is stored mainly in the liver in amounts (3-5mg) sufficient to last a

couple of years.


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Function of vitamin B121) Vitamin B12(as deoxyadenosylcobalamin) is a co-enzyme

methylmalonyl CoA mutase.


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Anaemia due to a true folic acid deficiency it is megaloblastic anaemia.

Effects of B12DeficiencyImpaired methylmalonyl CoA mutase causes accumulation of

unusual odd number carbon fatty acids.

These accumulate in nerve cell membranes causing irreversible

neurological disorders.

Impaired methionine synthase traps H4folate as N5-methyl-H4folate("folate trap").

This can lead to a secondary or artificial deficiency of folic acid.

One of the main symptoms of folic acid deficiency is anaemia.

Anaemia due to a true folic secondary folic acid deficiency caused

by primary B12 deficiency is pernicious anaemia


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2) Vitamin B12is also a coenzyme in a reaction involved in methionine

Metabolism.

H4folate is converted to N5-methyl-H4folate in a number of different reactions as it

accepts methyl groups. The methyl group can only be removed and the H4folate

regenerated by the above reaction.

(See folic acid)


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Deficiency of vitamin B12

Treatment is life long injections of vitamin B12

(oral administration wouldn't be much use!)

Dietary deficiency is rare (except for vegans).

Deficiency more commonly due to an absorptionproblem.

Auto immune disease can destroys

the parietal cells that secrete theI.F.required for absorption.


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Anaemia could be due to folic acid deficiency or

vitamin B12 deficiency.

In either case folic acid would cure the anaemia but if the true

underlying deficiency involved vitamin B12the patient wouldstill go on to develop the irreversible neurological disorders.

For this reason such patients are always given

folic acid andvitamin B12supplements until the true cause

of the anaemia is identified.

FOLIC ACID (FOLATE)


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FOLICACID (FOLATE)

A moderately high intake of folic acid is not toxic but might

mask an underlying vitamin B12deficiency that only becomesapparent once the irreversible neurological disorders set in

(see above).

Dietary sources and recommended intake:

Green leafy vegetables, liver, nuts and whole grain cereals.

RNI = 200g/day.

Large doses of folic acid (>1000g/day) canantagonise anticonvulsants

which could cause problems for epileptic people.


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STRUCTURE OF FOLICACIDFolic acid = pteridine base attached to p-aminobenzoic acid and glutamic acid.

Animals cannot make p-aminobenzoic acid or attach glutamic acid toaminobenzoic acid and all our folic acid is ultimately derived from

microbial and plant sources.the one already present.

Folic acid carrying polyglutamic acid cannot be transported back out of

the cell):


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Megaloblastic anaemia and folic

acid deficiency

Pernicious anaemia due to primary deficiency of vitamin B12giving

secondary deficiency of folic acid because all the folate ends up trapped

as N5-methyl-tetrahydrofolate

Folic acid deficiency reduces the capacity of the body to make

dTMP which affects the rapidly dividing bone marrow cells associated

with red blood cell production.

Importance of folic acid during early pregnancy:

Closure of the neural tube occurs around the 28th day of pregnancy

Incidence of neural tube defects (spina bifida and anencephaly) is reduced

by 400g folic acid supplement/day before conception and during the

first month of pregnancy.


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Folic acid

Its active form is tetrahydrofolate which

plays a role in transportation of one-carbon units to synthesize some

important substances.

Obat Antianemia Warmadewa 2012 Drugs

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