This document discusses iron and iron deficiency. It provides information on: 1. Iron is essential for hemoglobin formation and is involved in many enzyme systems. Iron deficiency can cause microcytic hypochromic anemia. 2. Causes of iron deficiency include blood loss, inadequate intake, and malabsorption. Good dietary sources include meat, fish, and plant sources like spinach. 3. Oral iron is usually sufficient to treat iron deficiency anemia, though parenteral iron may be needed in cases of malabsorption or intolerance. Different oral and parenteral iron preparations are available.

1. IRON

2. Reduced oxygen carrying capacity of the blood due to various reasons
including reduced Hb content or reduced number of RBCs or abnormal
RBCs..
 Can be due to:
i. Decrease RBC production
ii. Increase RBC destruction
iii. Blood loss
iv. Bone marrow depression & due to radiation, toxins & cytotoxic drugs
ANAEMIA

3.  Iron forms the nucleus of the iron-porphyrin heme ring.
 Four iron-porphyrin heme ring + globin chains  Hemoglobin
 Iron deficiency: Microcytic Hypochromic Anemia.
IRON

4. ROLE OF IRON
Haemopoiesis / erythropoiesis
Myoglobin
Cytochrome
Catalase
Peroxidase
Metaloflavoproteins (including xanthine oxidase)
Mitochondrial enzyme (alpha glycerophosphate oxidase)
Also important for brain functions….

5. CAUSES IRON DEFICIENCY
Increase need Insufficient
intake
Decreased
absorption
Adolescence Vegan diet High gastric pH
Menstruation Limited diet
(cabbage soup)
Gastric surgery
Pregnancy Malnutrition Vit. C deficiency
Lactation
Cancer

7. SOURCE OF IRON
• Meat, Liver,
• Chicken, Fish,
• Egg yolk, Oyster…
Animal
sources
• Wheat germs, Dry fruits,
• Spinach, Dried beans,
Apple, Banana, Jaggery,
• Milk & Milk products..
Plant
sources
MEAT IRON IS HEME IRON AND EASILY ABSORBED

8. Absorption:
PHARMACOKINETICS OF IRON
Dietary requirement – 10 to 20 mg / day (as only 5 – 10% is absorbed)
Absorption – Duodenum & Upper (proximal) jejunum
Absorption increased in iron deficiency
Heme iron (iron in meat) better & faster absorption, no need dissociated
Inorganic iron (veg/grain) poorly absorbed, bound to organic compounds
 needs to be dissociated to elemental iron
Non-heme iron (ferric form)  converted by ferro reductase  heme iron
acid (ferrous form)

9. Iron absorbed by active transport by apoferritin (upper GIT)
Ferrous iron oxidized in mucosal cells to ferric iron (ferroxidase)
Ferric iron (Fe3+) + apoferritin  Ferritin (non toxic)
Iron is slowly released from ferritin
Transported to bone marrow to synthesis of Hb
Controlled by regulating absorption according to need
PHARMACOKINETICS OF IRON
Absorption:

10. FACTORS THAT INFLUENCE IRON ABSORPTION
INCREASE ABSORPTION DECREASE ABSORPTION
Ascorbic acid Antacids
Amino acids Phosphates (egg yolk)
Meat Phytates (phytic acid),
Tannins
Increase gastric acidity
(appr. pH=2)*
Tetracyclines, Milk
Iron deficiency state Presence of food in stomach
*Jacobs & Miles, Gut 1969, 10: 226-229.

11. Iron transport via glycoprotein Transferrin
2 molecules of ferric iron (Fe3+) + transferrin  complex  engulfed by RBC’s
There is increase in transferrin levels during iron deficiency
PHARMACOKINETICS OF IRON
Transport :
Excess iron is stored as:
Ferritin (non toxic) in intestinal mucosal cells
Hemosiderin (aggregated ferritin, toxic) in liver, spleen & bone marrow
Storage:
Apoferritin +
Fe3+
Ferritin
Haemosiderin
(not reutilized)

12. DISTRIBUTION OF IRON IN THE BODY
Distribution of iron in the body
Hb 66 %
Ferritin,
Haemosiderin
25%
Myoglobin
(in muscle)
03%
Enzymes
(Cytochromes,
etc.)
06%
ADULT 2.5 - 5 g
MEN 50 mg/kg
WOMEN 38 mg/kg

13. IRON METABOLISM

14. BODY IRON REGULATION BY HEPCIDIN
1 Body iron decrease
lowers hepcidin
synthesis in the liver
3 Duodenal absorption of iron
increases
4 Splenic iron is released into
the circulation
5 Iron concentration in plasma
increases, leading to
restoration of iron balance
Hepcidin deficiency
targets the
duodenum and
spleen
2
Iron Deficiency
Hepcidin
1
2
3
4
Iron
Ganz T, et al. Am J Physiol Gastrointest Liver Physiol. 2006;290:G199-G203.
5

15. PHARMACOKINETICS OF IRON
Excretion :
No metabolism to excrete excess iron
Adult Male  0.5-1 mg
Adult female  1-2 mg
Pregnancy & lactation  3-5 mg

16. DAILY REQUIREMENT OF IRON IN THE BODY
Daily requirement of iron
Infant 0.06 mg/ kg
Children 0.025 mg/ kg
Adult male 0.5 - 01 mg
Adult female 01 - 02 mg
Pregnancy &
lactation
03 - 05 mg

17. Oral or Parenteral iron preparations.
REMEMBER!!!
Oral iron corrects the anemia just as rapidly and completely as
parenteral iron.
Sustained release formulations not rational…
IRON THERAPY

18. WHEN TO USE IRON ???
1. Treatment or prevention of iron deficiency anemia.
2. Premature infants & children
3. Pregnant & lactating women
4. Patients with chronic kidney disease (CKD)
5. Gastrectomy & severe small bowel disease
6. Blood loss
7. Megaloblastic anemia

19. AIM OF TREATMENT OF IRON DEFICIENCY ANAEMAI
Correction of Hb
Correction of the underlying cause
Building up body iron stores

20. TYPES OF IRON PREPARATIONS
IRON PREPARATIONS
ORAL
FERROUS SULPHATE,
FERROUS FUMARATE,
FERROUS GLUCONATE,
COLLOIDAL FERRIC
HYDROXIDE,
CARBONYL IRON
PARENTERAL
IRON DEXTRAN,IRON
SORBITOL CITRIC ACID
COMP., IRON SUCROSE &
SOD. FERRIC GLUCONATE,
FERRIC CARBOXYMALTOSE
& FERUMOXYTOL

21. Preparation of choice due to efficacy, safety, low cost
Dose/Tab Ele.Fe Daily dose
Fe. sulphate 325 mg 65 mg 2 - 4 tab
Fe. gluconate 325 mg 36 mg 3 - 4 tab
Fe. fumarate 325 mg 106 mg 2 - 3 tab
Colloidal ferric hydroxide 50 mg/ml drops.
Carbonyl iron: highly purity metallic iron prepared by
decomposition of iron pentacarbonyl  a highly toxic compound.
Ferrous sulphate – most effective, low cost & better absorption...
ORAL IRON

22. OTHER FORMS OF IRON PRESENT IN ORAL FORMULATIONS
Ferrous succinate (35% iron)
Iron choline citrate
Iron calcium complex (5% iron)
Ferric ammonium citrate (20% iron)
Ferrous aminoate (10% iron)
Ferric glycerophosphate
Ferric hydroxyl polymaltose
Better absorption, less bowel upset, lower iron content

24. Ferrous (Fe2+) form readily absorbed than ferric (Fe3+) form..
Ascorbic acid increases absorption, but therapeutically not useful
Caution:
Many FDC containing Iron & Vit. C are available.
They are costly and not advantageous.
ORAL IRON

25. Food impairs absorption, but still given with or after meals
Reason:
Causes less GI upset, as less is absorbed  Hence improves compliance.
Absorbed in duodenum and upper jejunum.
Clinical implication:
Delayed / modified release preparations release iron in lower part of small
intestine their iron content lower down…
So no therapeutic advantage.
ORAL IRON

26. Phytates, tannins – impair absorption
Clinical implication:
Advice patient not to take tablet along with tea.
Drugs can also impair absorption, e.g.
Levodopa,
Penicillamine,
Fluoroquinolones,
Tetracyclines,
ORAL IRON

27. DOSE OF ORAL IRON
Therapeutic:
Adult 200 mg/day in 3 divided doses with or after meals
Children  3-5mg/kg elemental iron/day in divided doses
Prophylaxis:
Pregnancy: 100 mg elemental iron daily from 2nd trimester.
Continue throughout lactation.
Professional Blood donors: 300 mg ferrous sulphate for 1 month after donating 500 ml.

28.  Early  increase in appetite & well being  2 days
 reticulocyte count  5 to 7 days…
 Evidence of adequate response
– Rise of Hb by 2 g/dl after 3 weeks of therapy..
RESPONSE TO THERAPY

29. Most common – GI disturbance,
heartburn,
nausea, vomiting,
bloating, colic.
Constipation, blackens the faeces
Metallic taste
Liquid formulation can stain the teeth
Clinical implication:
Should be taken by a straw, kept well inside the mouth.
ORAL IRON ADRs

30. Keep out of reach of children.
Reason:
 Children are very sensitive to iron toxicity (necrotizing gastroenteritis),
bloody diarrhea & later produce shock…
 Even 1 g of ferrous sulphate can be fatal.
Contraindications:
Hemolytic anemia
Ulcerative colitis
ORAL IRON PRECAUTIONS

31. Does NOT hasten Hb response
So indicated only in following conditions
-Malabsorption from gut (inflammatory bowel disease,
chronic inflammation…)
-Intolerable adverse effect
-Cannot be relied on to take tablets
-Presence of severe deficiency with chronic bleeding
-Severe anemia, with erythropoietin in kidney diseases patients
PARENTERAL IRON
Iron requirement (mg) = 4.4 x bw (kg) x Hb deficit (g/dl)

32.  Complex of ferric hydroxide with dextran.
 High molecular weight & given by IV & IM.
 IM in gluteal region by ‘Z’ track technique.
 Reaches RE cells via lymphatics.
 Need 25 % extra than calculated dose.
 Not excreted in urine & bile.
 Not preferred now a days because of high
incidence of fatal anaphylaxis.
IRON DEXTRAN

33. IRON DEXTRAN Cont…
Intramuscular:
2 ml (100 mg) daily or alternate days
Intravenous:
Test / Initial dose 0.5 ml over 5-10 min.
2 ml/ day over 10 min.
Total dose i. v. infusion
Dilute total calculated dose in 500 ml of 5% glucose/ Saline infuse
i.v. @ 10 drops /min. & ↑ to 30-40 drops/ min over 6-8 hrs.

34. IRON – SORBITOL CITRIC ACID COMPLEX
Low molecular weight complex
IM/ IV
Enters RE cells from blood
30 % excreted in urine
CI in Kidney disease

35. IRON SODIUM GLUCONATE
Preferred agent for parenteral (i.v) therapy, 80% delivered to
transferrin within 24 hrs.
FERROUS (IRON) SUCROSE
Complex of ferric hydroxide with sucrose. Given by slow i.v. inj. /
infusion  cause severe may occur drugs for resuscitation &
anaphylaxis.
Do not give oral ferrous concurrently & up to 5 days…..

36. IRON SUCROSE (cont..)
Not preferred by intramuscular route
Reason:
Can cause soft tissue sarcomas
Most likely among all iron preparations to cause renal tubular injury
Reason:
Has a high renal uptake

37. FERUMOXYTOL
 Carbohydrate – coated, superparamagnetic iron oxide
nanoparticle (little free iron is present in the preparation)
 Administered intravenously
 In 2009, FDA was approved by this drug for i,.v.
 Mainly in treatment of anaemia of chronic kidney disease (CKD).
 It interfere with MRI study.

38. FERRIC CARBOXYMALTOSE (FCM)
 Colloidal iron preparation embedded within a carbohydrate
polymer.
 Administered intravenously
 In 2013, FDA was approved by this drug for I.V.
 Mainly in treatment of anaemia of chronic kidney disease (CKD).

39. Most common – headache, vomiting, pain at site of injection,
skin pigmentation
Most serious – anaphylaxis
Others – hypotension
Precautions
Always administer test dose
Observe the vital signs during infusion
Be ready with measures for resuscitation
PARENTERAL IRON- ADRs

40. ACUTE IRON POISONING
Mainly Children and infants
Ferrous sulphate > 1g
Signs/ Symptoms:
 Vomiting, Diarrhoea, Abdominal pain, Dehydration, Acidosis, Lethargy,
Convulsion, CVS Collapse, Coma, Death (6-48 hours)
Haemorrhage & inflammation in the gut, liver necrosis, brain damage..

41. ACUTE IRON POISONING
To prevent further absorption of iron from gut:
Gastric lavage with sodium bicarbonate solution
Egg yolk & milk  orally to complex iron.
Activated charcoal does not absorb iron molecules.

42. ACUTE IRON POISONING
To bind & remove iron already absorbed:
Overdose of iron  oral & parenteral Desferrioxamine  a potent iron chelating agents.
50 mg /kg, IM; repeat 4-12 hrs…
 If shock : 10-15 mg/kg/ hr  max 75 mg/kg in a day till serum iron falls below 300 μg /dl
Calcium edetate
BAL is contraindicated  its iron chelate is also toxic
Supportive measures:
Maintain electrolyte balance  IVF & Diazepam  I.V. used to control convulsion ..

43. MISCELLANEOUS / ADJUVANT HAEMATINICS
Copper
Pyridoxine (Vit B6)
Riboflavin (Vit B2)