ANTI ANEMIC DRUGS

ISWANDI DARWIS
FACULTY OF MEDICINE
LAMPUNG UNIVERSITY
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ANEMIA
Decrease
Hemoglobin
concentration

Decrease
Hematocrite

Decrease
erytrosite
count
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CLASSIFICATION OF MORFOLOGY

Hipochromic
mikrocytic
Normochromic
normocytic

Makrocytic

MCV<80 fl
MCH<27pg
MCV 80-95/ fl
MCH 27-34 pg
MCV >95 fl
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ETIOLOGY
Erythropoesis
disorder
Bleeding

Hemolitic

Main causes

TYPES OF ANEMIA
Iron deficiency anemia
microcytic , hypochromic
Megaloblastic anemia

macrocytic , normochromic
due to Vit. B12 or Folic Acid deficiency
Anemia due to decreased Erythropoietin
as in chronic renal failure
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ANTI-ANEMIC DRUGS
Drugs effective in iron Iron
deficiency and other Pyridoxine , Riboflavin ,
hypochromic anemias Copper

Vitamin B12
Drugs effective in
megaloblastic anemia Folic Acid

Hematopoietic
growth factors

Erythropoietin

Iron Cycle
5 - 10% of ingested iron
is absorbed
Once ingested the acid
in the stomach:
Aids in ionization of iron
Splits chelated food iron
from chelator
Maintains iron in soluble
form
Allows iron to remain in the
absorbable form Fe3+
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Mechanism of Iron Absorption

IRON
Preparation

Oral

Parenteral

Ferrous sulphate
Ferrous gluconate
Ferrous fumarate

Iron dextran ---- i.m or i.v

Iron Sorbitol ----- i.m only
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IRON
Pharmacokinetic
Absorption ---- depends on
requirements
iron stores
Ferrous (Fe++) / ferric (Fe+++) form
pH
Vitamin C
Chelators or complexing agents
Malabsorption syndrome

Distribution
Transferrin
A beta-globulin , transport iron in plasma,
specifically bind ferric iron

Excretion
No mechanism for excretion of iron
Small amounts --- lost by exfoliation of
intestinal mucosal cells into stool.
Trace amounts --- excreted in bile , urine , & sweat.
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IRON
Indication
Pregnant , lactating , or menstruating women
Growing children & adolescence

Infants , especially premature infants

Malabsorption ---- gastrectomy,
severe small bowel disease
Occult G.I. bleeding ----- G.I. Cancer

Dietary deficiency
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IRON
Adverse effects
Abdominal
pain

Nausea
Either
constipation or
diarrhea.

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IRON
Toxicity
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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IRON
Clinical effect
Early changes

Vomiting, diarrhea
Acidosis from Iron oxidation

Intermediate
changes

Improvement (short lived) profound shock

and CV Collapse Hepatic Failure, jaundice,
pulmonary edema and death

Late Stage

Intestinal scarring, fatty acid degeneration of

liver, cirrhosis and death.
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VITAMIN B12
Porphyrin-like ring with a central cobalt atom & nucleotide
Cobalamins = various organic groups covalently bound to
cobalt atom
Active forms of vitamin B12 in human
Deoxyadenosylcobalamin
Methylcobalamin

Vitamin B12 available for therapeutic uses

Cyanocobalmin
Hydroxycobalamin
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VITAMIN B12
Defisiensi Effect

Impairment of DNA synthesis

affects all cells but most apparently
RBCs
Megaloblastic Anemia
GI symptoms
Neurologic abnormalities
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VITAMIN B12
Pharmacokinetic

Absorption:
Distibution

Intrinsic factor (IF) --- a glycoprotein ,

secreted by parietal cells of gastric mucosa
IF-Vit.B12 Complex --- absorbed by
active transport in the distal ileum

Transported in plasma bound to the glycoprotein transcobalamin

II
stored in hepatocytes

not significantly metabolized

Metabolism

Elimination:

pass into bile

Enterohepatic circulation
Excreted via kidney
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VITAMIN B12
Clinical Uses
Pernicious Anemia

Impaired GI absorption of B12

Gastrectomy
Corrosive Injury of GI mucosa
Fish tape worm: worm siphons off B12

Placebo abuse with B12, especially in elderly patients.

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Folic Acid
Source in food yeast, egg yolk, liver and leafy
vegetables

Folic Acid (F.A.) is absorbed in the small intestines

F.A. is converted to tetrahydrofolate by dihydrofolate

reductase
Functions : required for synthesis of Amino acids ,
purines, pyrimidines, & DNA ; & therefore in the cell
division
Deficiency may produce megaloblastic anemia; neural
tube defect in fetus
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Folic Acid
Deficiency Features

Mitotically active
tissues such as
erythroid tissues are
markedly affected.

Anemia

Congenital
malformations
neural tube defects

Vascular disease
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Folic Acid
Therapeutic Uses
Megaloblastic Anemia due to inadequate dietary intake of folic acid
Can be due to chronic alcoholism, pregnancy, infancy, impaired utilization: uremia, cancer or
hepatic disease.
To alleviate anemia that is associated with dihydrofolate reductase inhibitors.
i.e. Methotrexate (Cancer chemotherapy), Pyrimethamine (Antimalarial)
Administration of citrovorum factor (methylated folic acid) alleviates the anemia.
Ingestion of drugs that interfere with intestinal absorption and storage of folic acid.
Mechanism- inhibition of the conjugases that break off folic acid from its food chelators.
Ex. phenytoin, progestin/estrogens (oral contraceptives)
Malabsorption Sprue, Celiac disease, partial gastrectomy.

Rheumatoid arthritis increased folic acid demand or utilization.

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Folic Acid
Pharmacokinetics

Route of administration usually oral

Absorption must be converted to
Monoglutamyl form
Absorbed mostly in proximal jejunum
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Folic Acid
Clinical Uses
Dietary insufficiency (e.g. in elderly)
Pregnancy & lactation
to prevent Congenital malformations neural tube defects ( e.g.,
spina bifida)
Premature infants

Malabsorption syndromes
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ERYTHROPOIETIN (EPOTEIN)
a glycoprotein hormone
produced : 90% by peritubular cells in kidney
and remainder - by liver and other tissues
essential for normal reticulocyte production

synthesis is stimulated by hypoxia

synthesized for clinical use ---- by
recombinant DNA technology
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Pharmacokinetic
Route of
administration --S.C. or I.V.

Plasma t1/2 ---- 4 13 hrs in patients

with chronic renal
failure.

Not cleared by
dialysis
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Mechanism of Action

increases rate
of stem cell
differentiation

increases rate
of mitosis in red
cell
precursors,blastforming units,
colony forming
cells.

increases
release of
reticulocyte
from marrow

increases Hb
synthesis

its action
requires
adequate stores
of iron

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Clinical Uses
Anemia associated with chronic renal failure
premature infants
Anemia during chemotherapy of cancer
Anemia of AIDS (which is exacerbated by zidovudine treatment)
to increase the yield of autologous blood before donation
Anemia of chronic inflammatory conditions such as rheumatoid arthritis
MISUSED --- by sports people

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Adverse effects
Transient
influenza-like
symptoms chills
& myalgias

hyperkalemia

iron deficiency

transient increases
in platelet count

skin rashes

pure red cell

aplasia
discontinue the
drug

antibodies to
epoetins

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Precautions / contraindications
hypertension should be well controlled

seizures
thrombocytosis
ischemic vascular disease
iron , folic acid , vit. B12 supplements may be

Needed heparin during dialysis

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Thanks

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