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
6.
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
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
23.
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 ..