Haematinics

Pharmacology of Haematinics

Haematinics: These are the substances required in the formation of blood and are used in the treatment of anemia.

Anemia defined as a reduced concentration of hemoglobin (Hb) in the blood.

Anemia:

· It gives rise to fatigue.

· It occurs when the balance between production and the destruction of RBC’s is disturbed by

(a)Blood Loss (acute or chronic)

(b)Impaired red cell formation- which is due to

• Deficiency of essential factors (i.e. iron, Vit B12, Folic acid)

• Bone marrow depression (hypoplastic anemia), erythropoietin deficiency

• Increased destruction of RBC’s (hemolytic anemia)

Iron:

Distribution of Iron in body: Iron is essential body constituent.

Total body Iron for

• Adult 2.5 – 5 gm (avg 3.5 gm)

• Men 50 mg/kg

• Women 38 mg/kg

Iron is distributed into,

1. Hemoglobin (Hb) - 66%

2. Iron stores as ferritin & hemosiderin - 25%

3. Myoglobin (in muscles) - 3%

4. Parenchymal iron (in enzymes, etc) - 6%

• Each Hemoglobin molecule ====> has 4 iron containing heme residues.

• Iron is stored only in ferric form, in combination with a large protein “Apoferritin”

• Apoferritin + Fe+3 ====> ferritinè -----> aggregates -----> to form ====> hemosiderin

The most important storage sites of iron ====> is Reticuloendothelial cells (RE)

Dietary Sources of iron:

Rich Sources: Liver, egg yolk, oyster, dry beans, dry fruits, wheat germ, yeast

Medium Sources: Meat, chicken, fish, spinach, banana, apple

Poor Sources: Milk and its products, root vegetables

Iron Absorption:

• Average daily diet contains 10-20 mg of iron.

• Absorption occurs all over intestine, but mainly upper part of intestine.

• Dietary iron present either as, “heme” ====> (as smaller portion) or as inorganic iron ====> (as major portion).

Absorption -----> of heme iron is better, up to 35% compared to inorganic iron which averages 5%.

Absorption occurs without the aid of a carrier

Iron ====> is reduced ====> to ferrous form ====> then ====> absorbed.

Factors facilitating Iron absorption:

1) Acid: by favoring dissolution and reduction of ferric iron.

2) Reducing substance: ascorbic acid, amino acid containing SH radical.

These agents reduce ferric iron and form absorbable complexes.

3) Heat: by increasing HCl secretion & providing heme iron.

Factors impeding Iron absorption:

1) Alkalies (antacids) render iron insoluble, oppose its reduction

2) Phosphates (rich in egg yolk) ====> by complexing iron

3) Phytates (in maize, wheat) ====> by complexing iron

4) Tetracyclines ====> by complexing iron

5) Presence of other foods in the stomach

Transportation, Utilization, Storage & Excretion:

• Free iron is highly toxin.

• Iron -----> enters into -----> plasma --- in -----> ferric form.

• This ferric form binds with -----> Transferrin (Tf) (which is a glycoprotein) ====> to form a complex.

• Iron circulates in plasma bound to Transferrin (2 Fe+3 residues per molecule)

• Erythropoietic & other cells -----> have specific membrane bound Tf receptors (TfRs)

• Tf ----->binds to ----->TfRs ====> thus helps in iron transportation into those cells.

• Receptor mediated endocytosis occurs-----> which results engulfing of the complex.

• Intracellular vesicles-----> have -----> acidic pH -----> therefore iron dissolves from complex at this pH.

• Iron released from the complex -----> used for Hemoglobin synthesis or other purposes.

• And Tf & TfRs -----> returned to cell surface to carry fresh loads.

Iron is stored in RE cells in liver, spleen, bone marrow. And also in hepatocytes & myocytes as ferritin & hemosiderin after entering these cells through TfRs.

Iron tenaciously conserved by the body.

Daily excretion in adult Male is -----> 0.5 – 1 mg, in menstruating women, monthly menstrual loss may be averaged to 0.5 – 1 mg/day.

Unwanted Effects:

• Unwanted effects of oral iron administration -----> are -----> dose related like -----> nausea, abdominal cramps & diarrhea.

• In young children -----> “acute iron toxicity” -----> occurs after ingestion of large quantities of iron salts.

• This leads to severe necrotizing gastritis with vomiting, hemorrhage & diarrhea, followed by circulatory collapse.

• Chronic iron toxicity or iron overload -----> are also due to -----> conditions other than ingestion of iron salts.

• Treatment for acute/chronic iron toxicity -----> is by use of iron chelators such as “desferrioxamine”.

• Desferrioxamine + ferric iron ====> forms a complex ------> which is excreted in urine.

Uses of Haematanics :

1. In iron deficiency anemia caused by,

• Chronic blood loss (e.g. , with menorrhagia, hook worm, colon cancer

• Increased demand (e.g., in pregnancy & early infancy )

• Inadequate dietary intake

• Inadequate absorption (e.g., following gastrectomy)

2. Megaloblastic Anemia: - when brisk hemopoiesis is induced by Vit B12 or folate therapy, iron deficiency may be unmasked. The iron status of this patient should be evaluated & iron given accordingly.

3. As an astringent: ferric chloride is used in throat pain.