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INTRODUCTION
Haemetinics.
The most important site of formation of red blood
cells in adults is the bone marrow.
The process by which the formation of RBCs
occurs is known as erythropoesis.
ERYTHROPOESIS
Monitoring of oxygen level in the blood is carried
out by kidney.
Contd.
FOR ERYTHROPOESIS BODY NEEDS
Iron
Folic acid
Vit.B12
Erythropoietin
IRON
As part of the protein haemoglobin
Iron also helps our muscles store and use oxygen.
Iron is a part of enzymes
Act as electron transporter: Vital for life.
Must be in ferrous (Fe+2) state for activity. Ferric (Fe+3)
ions cannot transport electrons or O2
DISTRIBUTION OF IRON IN
THE BODY
Total body iron in the adult is 2.5-5 gm
Blood circulation
Fe
Fe Fe Fe
Fe2+
Fe3+ Fe
Fe3+
Ferritin
Fe
Fe
Fe
Fe Fe
Fe Fe
Fe Fe Fe Fe
Fe Fe BOUND TO APOFERRITIN
TRANSFERRIN
Bone marrow
Fe
Fe
for use or storage
TRANSFERRIN
IRON DEFICIENCY
Iron deficiency ranges from depleted iron stores without
functional or health impairment to iron deficiency with
anemia, which affects the normal motor function or mental
functions.
Signs and symptoms of iron deficiency
Feeling tired and weak
Slow cognitive and social development during childhood
Difficulty maintaining body temperature
Decreased immune function, which increases susceptibility
to infection
Glossitis (an inflamed tongue)
Contd.
Causes of deficiency:
1) Blood Loss
Gastrointestinal Tract
Menstrual Blood Loss
Urinary Blood Loss (Rare)
2) Increased Iron Utilization
Pregnancy
Infancy
Adolescence
Polycythemia
3) Malabsorption
Tropical Sprue
Gastrectomy
Chronic atrophic gastritis
UNWANTED EFFECTS
1) Oral
Nausea, Vomiting, Epigastric Pain, Heart burn, Metallic
taste, Diarrhoea.
2) Parenteral
Pain at site of injection, Pigmentation of the skin, Fever,
Headache, Joint pain, Flushing, palpitation, Lymph node
enlargement.
Acute iron toxicity
Chronic iron toxicity
Treatment of acute and chronic iron toxicity
CLINICAL USES
Haemetinic
Astringent
Disinfectant
Arsenic antidote
Inadequate absorption (e.g. following gastractomy)
Chronic blood loss (e.g. with menorrhagia, hookworm,
colon cancer)
Increased demand (e.g. in pregnancy and early infancy)
Inadequate dietary intake (uncommon in developed
countries)
IRON PREPARATIONS
A)Iron chelators
• sodium ferredetate
• ferric tri glycinate
• ferrous bi glycinate
B) Iron amino acid complexes
• Ferrous Aminoate
• Ferrous Glycine sulphate
• Ferrous Succinylate
C) Iron complexes
• Ferrous Gluconate
• Iron Dextran Fe content :15%
• Iron Sorbitrol Citric Acid Complex
Vitamin B12
Vitamin B12 belongs to the family of cyanocobalamine
Serves as a cofactor for two important reactions in humans
The vitamin B12 used medically is hydroxocobalamin.
Vitamin B12 is carried in the plasma by binding proteins
called transcobalamins.
The daily absorption of vitamin B12 is 5 mcg/day
PHARMACOKINETIC
ASPECTS
Vitamin B12 is present in the food as a protein conjugates.
Gastric acid and proteolytic enzymes release free vitamin
B12 in the stomach and duodenum. Parietal cell of stomach
secrete a specific glycoprotein known as intrinsic factor.
Which forms a complex with vitamin B12(extrinsic factor)
this complex is absorbed in the distal ileum by a highly
specific receptor mediated transport system
Storage and excretion:
Excess vit. B12 is stored in the liver. If for any reason any
intestinal Vit. B12absorption is stopped, the normal hepatic
store will last for 5 years. It is only after this period that
deficiency anemia will be manifested.Vit- B12 is excreted
in bile but most of reabsorbed by enterohepatic circulation.
Contd.
Biochemical reactions
Vitamin B12 is required for two main biochemical reactions:
1) Conversion of methyl-FH4 to FH4 .
2) Isomerisation of methylmalonyl-CoA to succinyl-CoA
Causes of deficiency
Decreased production of intrinsic factor
Gastrectomy
Helicobacter pylori infection
Crohn's disease
Vitamin B12 requirement also increased in pregnancy,
thyrotoxicosis, hemolytic anemia, hemorrhage,
malignancy, liver or kidney disease.
CLINICAL USES
Vit. B12 is used in treatment of:
Pernicious anemia
Megaloblastic anemia
As dietary suppliments
FOLIC ACID
Folic acid is the term commonly used for
pteroylmonoglutamic acid.
In its reduced form of tetrahydrofolate, it serves as an
important mediator of many reactions.
Some aspects of folate structure and metabolism are deal
with several important antibacterial and anticancer drugs
that interfere with folate synthesis in micro-organisms.
Daily requirements of Folic acid is 50–100 mcg/day.
CAUSES OF DEFICIENCY
Dietary deficiency
Decreased absorption
Chronic hemolytic anemia
Pregnancy
Malabsorption due to drugs: phenytoin, phenobabarbiton,
isoniazide, and oral contraceptives
Use of anti-folate compounds: methotrexate or rarely of
pyrimethamine and trimethoprime, prevent conversion of
H2 folate to H4 folate
PHARMACOKINETIC
ASPECTS
Dietary folate, which is primarily polyglutamate form of
tetahydro folate, is hydrolyzed by the enzyme –
glutamyltransferase,within the brush border of the
intestinal mucosal. Ascorbic acid protects the active H4
folate from oxidation. Tetrahydro folate is absorbed as
monoglutamate and transported bound to folate binding
plasma protein. It is utilized in the tissues, and stored in the
liver.
Folic acid undergoes enterohepatic circulation.Trace
amount of folic acid are excreted in the urine and stool.
BIOCHEMICAL REACTION
Dihydrofolate (FH2) and tetrahydrofolate (FH4) act as
carriers and donors of methyl groups (1-carbon transfers)
in a number of important metabolic pathways. For
example, FH4 is essential for DNA synthesis because of its
role as cofactor in the synthesis of purines and
pyrimidines. It is also necessary for reactions involved in
amino acid metabolism.
The role of folate and vitamin B12 in the conversion of
homocysteine to methionine has been implicated in the
role of elevated blood homocysteine concentrations and
premature CVD as well as premature occlusive vascular
disease.
CLINICAL USES
Treatment of megaloblastic anaemia resulting from folate
deficiency
Treatment or prevention of toxicity from methotrexate, a
folate antagonist
Prophylactically in individuals at hazard from developing
folate deficiency, for example: pregnant women and before
conception (especially if there is a risk of birth defects)
premature infants
Patients with severe chronic haemolytic anaemias,
including haemoglobinopathies (e.g. sickle cell anaemia).
HAEMOPOETIC GROWTH
FACTORS
1) Erythropoetin
2) Colony-stimulating factors
1) ERYTHROPOETIN
Erythropoietin the first haemopoietic growth factor to be isolated
and characterized from urine of severely anaemic patients.
It is a 165 amino acid peptide produced by using recombinant
DNA technology. And is a 165 amino acid peptide
Erythropoietin is produced in Juxtatubular cells in the kidney and
also in macrophages.
Its action is to stimulate generation and proliferation of RBC.
Erythropoietin (EPO) is a sialoglycoprotein hormone
Anaemia and hypoxia are sensed by kidney cells, rapid secretion
of EPO and act on erythroid marrow:
Stimulates proliferation of colony forming cells of erythroid
series.
It regulate the blood cell proliferation & differentiation in
bone marrow.
Induces haemoglobin formation and erythroblast maturation.
Like EPO , another factor that colony stimulating factor have been
identified that stimulate bone marrow production of RBC,
granulocytes, macrophages & platelet
2) COLONY-STIMULATING FACTORS
Mechanism of action:
GCSF has ability to mobilize haematopoietic stem cell and
increase their concentration in peripheral circulation.
GM-CSF is multipotential haematopoietic growth factor which
stimulates proliferation and differentiation of progenitor cells of
granulocytes and erythrocyte.
GCSF activate phagocytic activity of neutrophills and prolong
their life span in circulation.
ACTION: