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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.
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