NORMAL VALUE

 For men, anemia is typically defined as hemoglobin level of less than

13.5 gram/100ml
 For women hemoglobin of less than 12.0 gram/100ml
 Normal life span of a red blood cell is typically around 120 days.

ANEMIA
 Anemia is defined as a below-normal plasma hemoglobin
concentration resulting from a decreased number of circulating red
blood cells or an abnormally low total hemoglobin content per unit
of blood volume.
 Anemia can be caused by chronic blood loss, bone marrow
abnormalities, increased hemolysis, infections, malignancy,
endocrine deficiencies, renal failure, and a number of other disease
states.
 A large number of drugs cause toxic effects on blood cells,
hemoglobin production, or erythropoietic organs, which, in turn,
may cause anemia

 Nutritional anemias are caused by dietary deficiencies of substances

such as iron, folic acid, and vitamin B12 (cyanocobalamin ) that are
necessary for normal erythropoiesis.

SYMPTOMS OF ANEMIA
Some people with anemia have no symptoms. Other people with
anemia may feel:
 Tired

 Fatigue easily

 Appear pale
 Develop palpitations (feeling of heart racing)
 Become short of breath
HEMATOPOIESIS
 Process that produces over 200 billion new blood cells
per day in the normal person
 Production from undifferentiated stem cells of
circulating erythrocytes, platelets, and leukocytes

HEMATOPOIETIC MACHINERY
 In the bone marrow requires a constant supply of three essential
nutrients
 Iron
 Vitamin B12
 Folic acid
 Hematopoietic growth factors
TYPES OF ANEMIA
 1. Iron deficiency
 2. Folate deficiency

 3. Vit B12 deficiency

 4. Anemia of chronic disease as uremia, erythropoieten

is used 50-150U/kg for 3 weeks
 5. Sickle cell anemia
 6. Thalasemia
 7. Aplastic anemia
 8. Autoimmune hemolysis as Hemolytic disease of the newborn
erythroblastosis fetalis treat by immunoglobulins.
 9. G6PD deficiency result in hemolysis (NSAIDS, Aspirin, quinine,
antimalarials, sulfonamides cause deficiency and ppt hemoglobin so
avoid)
IRON
 Iron is stored in intestinal mucosal cells as ferritin until
needed by the body.
 Iron deficiency results from acute or chronic blood loss,
from insufficient intake during periods of accelerated
growth in children, and in heavily menstruating or
pregnant women.
 Iron deficiency results from a negative iron balance due
to depletion of iron stores and/or inadequate intake,
culminating in hypochromic microcytic anemia (due to
low iron and small-sized red blood cells).
 Supplementation with ferrous sulfate is required to
correct the defi ciency.
ABSORPTOPN
 Intestine
 Iron absorbed as ferrous iron(Fe+2 ) Oxidised in mucosal cell to ferric
form (Fe+3)
 The average diet contains 10–15 mg of elemental iron daily
 A normal individual absorbs 5–10% of this iron, or about 0.5–1 mg daily

STORAGE AND EXCRETION

 Trivalent ferric ion stored in mucosa bound to ferritin
 Excess iron stored in reticuloendothelial system
 In parenchyma cells of skin, liver and other organs
 Accumulation of iron occurs in hemolytic anemia (RBCs
destruction) and hemochromatosis
 Minimum amount of iron excreted from sweet, saliva and skin
 IRON TOXICITY; ACUTE IRON
CLINICAL TOXICITY
INDICATION  Common in children
 High ingestion of iron
tablets
 Iron deficiency anemia  Necrotising
 Hypochromic
 Gastroenteritis
microcytic anemia  Vomiting
 Not in hemolytic  Abdominal pain
anemia and  Bloody diarrhea
hemochromatosis  Lethargy
 Dyspnea
 Metabolic acidosis
 Shock, coma and death
 TREATMENT OF IRON
CHRONIC IRON TOXICITY
TOXICITY
 Due to frequent  Removal of unabsorbed iron
transfusion as in from gut
sickle cell anemia  Correction of acid base and
 In hemochromatosis electrolyte abnormalities
 Parenteral administration of
 Inherited abnormality
deferoxamine
of iron absorption  For chronic toxicity as
hemochromatosis phlebotomy
SOME COMMONLY USED ORAL IRON
PREPARATIONS
 Preparation Tablet Size dose
 Ferrous sulfate, hydrated 325 mg tid

 Ferrous gluconate 325 mg tid

 Ferrous fumarate 325 mg tid
PARENTERAL IRON PREPARATIONS
 Iron dextran
 Stable complex of ferric hydroxide and low-molecular-
weight dextran
 Containing 50 mg of elemental iron per milliliter of
dextrose solution
 Deep intramuscular injection

 Intravenous infusion Cause hypersensitivity so

 Iron-sucrose complex and Iron sodium gluconate

complex used for IV
VITAMIN B12 (COBALAMIN)
 The average diet contains 5–30 mcg of vitamin B12 daily
 1–5 mcg of which is usually absorbed
 A cobalt containing molecule involve in step of DNA
synthesis
 Along with folic acid, i.e. a cofactor in transfer of 1
carbon unit
 Its deficiency results in anemia

 Irreversible Neurologic defects

PHARMACOKINETICS
 Produced by bacteria also
 Stored in liver and stores are enough for five
years
 Absorb from GI in presence of intrinsic factor
released from mucosal cells
 Plasma transport is by binding with
transcobalamin II
 Parentral Cyanocobamin and hydroxycobalamin

 Hyrdroxycobalamin has long plasma half life

PHARMACODYNAMI
CS METHYLMALONYL-COA
 Methyl melonyl Co A to  It is coenzyme A
Succinyl Co A  Methylmalonyl-CoA is formed
 Homocysteine to
from propionyl-CoA by
propionyl-CoA carboxylase by
methionine help of biotin (vitamin B7)
 Folic acid metabolism  It is converted into succinyl-
 Synthesis of CoA by methylmalonyl-CoA
mutase, in a reaction that
deoxythymidylate (dTMP)
requires vitamin B12 as a
involve in DNA synthesis cofactor
 In this way, it enters the Krebs
cycle
KREBS CYCLE
 In aerobic organisms
 The citric acid cycle is part
of a metabolic pathway
 Involved in the chemical
conversion of
carbohydrates, fats and
proteins into carbon dioxide
and water to generate a
form of usable energy
HOMOCYSTEINE
 Homocysteine can be recycled
into methionine
 This process uses N5-methyl
tetrahydrofolate as the methyl
donor and cobalamin (Vitamin
B12)-related enzymes
 Deficiencies of the vitamins folic
acid (B9), pyridoxine (B6), or B12
(cyanocobalamin) can lead to
high homocysteine levels leading
to cardiovascular diseases
ENZYMATIC REACTIONS
THAT USE FOLATES

 Section 1: Vitamin B12

dependent reaction
 Section 2: dTMP
cycle
 Section 3: Path way
by which folate enters
in to the
tetrahydrofolate
cofactor pool
VITAMIN B12 DEFICIENCY
 In vitamin B12 deficiency the folate accumulate
as N5-methyltetrahydrofolate
 Tetrahydrofolate supply depleted

 RBCs production is slow

 Administration of folic acid can treat anemia

partially or fully
 But not the neurologic defects of vitamin B12

deficiency
CLINICAL USES AND
TOXICITY
 Cause inadequate
absorption
 Parenteral
hydroxycobalamin and
cyanocobalamin
 Pernicious anemia
 Gastric resection anemia
 No significant toxicity
FOLIC ACID (VITAMIN B9)
OR FOLICIN
 Involve in DNA synthesis
as vitamin B12
 Deficiency results in
megaloblastic anemia
 Deficiency during
pregnancy results in
neural tube defect in fetus
PHARMACOKINETICS
 Absorb from GIT
 Less amount absorbed in body so with in months deficiency
lead to anemia
PHARMACODYNAM
ICS
 Folic acid by dihydrofolate reductase convert in to di and than in
tetrahydrofolate
 Di and tetrahydrofolate involve in synthesis of dTMP
 Rapidly dividing cells as DNA affected by folic acid deficiency
 Antifolates use in infections and cancers
 Methotrexate one of anticancer inhibit DNA synthesis by inhibiting
dihydrofolate synthesis
CLINICAL USE AND TOXICITY
 Deficiency due to dietary insufficiency or malabsorption
 Oral folic acid treat anemia

 It not treat nerologic deficit of vitamin B12 deficiency

 Folic acid in combination with vitamin B12 treat

megaloblastic anemia better
 No recognise toxicity
HEMATOPOIETIC GROWTH FACTORS
 A dozen of glycoprotein hormones that regulate
differentiation and maturation of stem cells within the
bone marrow
 Several growth factors that are produced by recombinant
DNA technology have FDA approval for blood cell
deficiencies
 All hematopoietic growth factors are protein

 Destroy by stomach acid and digestive enzymes

 Not administer orally

 IV, IM and S/c administration

HEMATOPOIETIC GROWTH
FACTORS
 1. ERYTHROPOIETIN
 2. MYELOID GROWTH FACTOR
 3. MEGAKARYOCYTE GROWTH FACTORS

1. ERYTHROPOIETIN
 Produced by kidney
 In renal failure decrease synthesis cause anemia

 It increase production of RBCs from bone marrow by

stimulating erythroid progenitor receptors in bone
marrow
 It also increase release of RBCs from bone marrow
CLINICAL USES
 Anemia of renal failure
 Anemia due to primary bone
marrow disorder
 Anemia secondary to cancer
chemotherapy
 HIV treatment of AIDS
 Bone marrow transplantation
TOXICITY
 Toxicity is rare and is
related to excessive
increase in hematocrit
 Darbopoietin alpha i.e.
a glycosylated form of
erythropoietin has
longer half life
2. MYELOID GROWTH FACTOR
 G-CSF (filgrastim) stimulate neutrophils production and
function
 GM-CSF (sargramostim) stimulate production of
granulocytes (basophils, eusinophils,neutrophils) and
other myeloid cells
 G-CSF and to lesser extent GM-CSF mobilize
hematopoietic stem cells i.e. increase their concentration
in blood
CLINICAL USES
 Both factors use to recover neutrophils after
chemotherapy
 Secondary and primary neutropenia as

 Aplastic anemia

 Congenital neutropenia

 G-CSF use after stem cell transplantation and Inhibit

neutropenia and Increase mobilization of PBSCs
(peripheral blood stem cells).
TOXICITY
 G-CSF show minimal toxicity Some time bone pain
 GM-CSC show more toxicity as
 Fever
 Arthralgia
 Capillary damage
 Edema
 Rare allergic reactions
 Pegfilgrastim has longer half life than filgrastim
3. MEGAKARYOCYTE GROWTH FACTORS
 Oprelvekin (interleukin-II or IL-II) increase growth of
megakaryocytic progenitors and
 Increase peripheral platelets

CLINICAL USE

 Treat thrombocytopenia after cancer chemotherapy

 It reduces need for platelets transfusion

TOXICITY
 Fatigue
 Headache
 Dizziness
 Fluid retention