PHARMACOLO

GY OF
IRON
BY: SALMA AHMED
 INTRODUCTION

IRON IS AN ESSENTIAL IT PLAYS A CRITICAL ROLE WITHIN A LARGE VARIETY IRON SUPPLEMENTS ARE
COMPONENT OF EVERY IN THE TRANSPORT AND OF ENZYMES IRON ALSO WIDELY ADMINISTERED TO
CELL IN THE BODY. STORAGE OF OXYGEN (IN ACTS AS A CARRIER FOR TREAT IRON DEFICIENCY
HEMOGLOBIN AND ELECTRONS, A CATALYST ANEMIA, PARTICULARLY IN
MYOGLOBIN), FOR OXYGENATION, CHRONIC DISEASES SUCH
RESPECTIVELY. HYDROXYLATION, AND IS AS KIDNEY DISEASE, HEART
NECESSARY FOR CELLULAR FAILURE OR
GROWTH AND INFLAMMATORY BOWEL
PROLIFERATION. DISEASE.
 DISTRIBUTION IN BODY

Total body iron in an Men(50 mg/kg) >

It is distributed
adult : 2.5-5 g (average Women(38
into:
3.5 g) mg/kg)

Iron stores as
Parenchymal
Hemoglobin(Hb) ferritin and Myoglobin (in
iron (in enzymes,
: 62% haemosiderin : muscles) : 7%
etc.): 6%
25%
 STORAGE
Hb- protoporphyrin, i.e, each molecule has 4 iron containing haem residues.
It has 0.33% iron.
Loss of 100 ml of blood (containing 15 g Hb) means loss of 50 mg elemental iron.
To raise the Hb level of blood by 1g/dl about 200 mg of elemental iron is needed.
Iron is stored only in ferric form, in combination with a large protein apoferritin.
aggregates
Apoferritin + Fe3+ Ferritin Hemosiderin (not reutilized)
Ferritin can get saturated to different extents; at full saturation it can hold 30% iron by
weight.
Most important storage sites are reticuloendothelial cells(RE).
 DAILY REQUIREMENTS

Adult female
Adult male : 0.5 –
(menstruating) : Infants : 60 µg/kg
1 mg (13µg/kg)
1-2 mg (21µg/kg)

Pregnancy (last 2
Children : 25
trimesters) : 3-5
µg/kg
mg (80 µg/kg)
 DIETARY SOURCES

Rich : Liver, egg yolk, oyster, Medium : Meat, chicken, fish, Poor : Milk and its products, root
dry beans, dry fruits, wheat spinach, banana, apple. vegetables
germ, yeast.
 IRON ABSORPTION

Average daily diet : 10-20 mg of iron.

Absorption occurs all over intestine, but majority in upper part.

Dietary iron present as :

1. Haeme
2. Inorganic iron
Absorption of haem iron(Upto 35%) > inorganic iron (5%)
 FACTORS AFFECTING
ABSORPTION
1. Factors facilitating absorption:

Acid, Reducing substances, Meat

2. Factors impeding absorption:

 Alkalis

 Phosphates (rich in egg yolk)

 Phytates(in maize, wheat) By complexing iron

 Tetracyclines

 Presence of other foods in the stomach

MUCOSAL BLOCK
TRANSPORT AND
UTILIZATION
EXCRETION
Daily excretion in adult male : 0.5 – 1 mg
Iron in body is excreted as:
oExfoliated gastrointestinal mucosal cells
oSome RBCs
oIn bile(lost as faeces)
oDesquamated skin
oVery little through urine and sweat

In menstrual women, monthly menstrual loss : 0.5 – 1 mg/day.

Excess iron is required during pregnancy for expansion of RBC mass, transfer
to fetus and loss during delivery, totaling to about 700 mg. This is met in later 2
trimesters.
IRON PREPARATION AND
DOSE
Iron is administered by several means:
 Oral route

 Parenteral route (i.v and i.m)

Preferred route of administration is oral route.

ORAL ROUTE OF
ADMINISTRATION
Dissociable ferrous salts are inexpensive, have high iron content and better absorbed
than ferric salts.

Examples of oral preparations:

1. Ferrous sulfate (hydrated salt 20% iron & dried salt 32% iron)
2. Ferrous gluconate(12% iron)
3. Ferrous fumarate(33% iron)
4. Colloidal ferric hydroxide(50% iron)
5. Carbonyl iron
6. Other forms of iron in oral formulations
oFerrous succinate(35% iron)
oIron choline citrate
oIron calcium complex (5% iron)
• Better absorbed
oFerric ammonium citrate(20% iron) • Produce less bowel upset
• Lower iron content
oFerrous aminoate (10% iron)
• More expensive
oFerric glycerophosphate
oFerric hydroxy polymaltose
•Elemental iron content should be taken into consideration, and not quantity of
iron compound per dose unit.
•A total of 200 mg elemental iron (infants and children 3-5 mg/kg) given daily
in 3 divided doses produce maximal hematopoietic response.
•Prophylactic dose is 30 mg iron daily.
•Absorption is better when iron is taken in empty stomach, but side effects are
more.
ADVERSE EFFECTS OF ORAL
IRON
Epigastric pain, Heartburn, Nausea, Vomiting, Bloating
Staining of teeth
Metallic taste
Colic
Constipation is more common than diarrhea (because of astringent action of iron). However, it can be
result of alteration of intestinal flora.
Tolerance to oral iron can be improved by initiating therapy at low dose and gradually escalating to
optimum dose.
 PARENTERAL IRON
ADMINISTRATION
Iron therapy by injection is indicated only when:
1. Oral iron is not tolerated: bowel upset is too much.

2. Failure to absorb oral iron: malabsorption; inflammatory bowel disease. Chronic inflammation (e.g. RA)
Fe absorption, as well as rate at which iron can be utilized.

3. Non-compliance to oral iron

4. In presence of severe deficiency with chronic bleeding.

5. Along with erythropoietin in chronic kidney disease(CKD) patients: oral iron may not be absorbed at
sufficient rate to meet the demands of induced rapid erythropoiesis.
 Parenteral iron therapy needs calculation of total iron requirement of patient.
 A simple formula is:
Iron requirement (mg) = 4.4 × body weight(kg) × Hb deficit (g/dl)

 This formula includes iron needed for replenishment of stores.

 Rate of response with parenteral iron is not faster than oral, except in first 2-3 weeks when
dose of oral iron is being built up.
 However, iron stores can be replenished in shorter time by parenteral therapy, because after
correction of anemia, a smaller fraction of ingested iron is absorbed.
Four organically complexed formulations of iron available in India are:

a. Iron-dextran(i.v. , i.m.)

b. Ferrous sucrose(i.v.)

c. Ferric carboxymaltose(i.v.)

d. Iron isomaltoside 1000(i.v.)

e. Iron sorbitol(i.m)
IRON-DEXTRAN
HMW colloidal solution - 50 mg elemental Fe/ml.
Route: I/M, I/V
By i/m route, it is absorbed through lymphatics, circulates without binding to transferrin and
is engulfed by RE cells where iron dissociates and is made available to erythron for haem
synthesis.
In injected muscle, 10-30% of dose remains locally bound and becomes unavailable for
utilization for several weeks. Thus, 25% extra needs to be added to calculated dose.
Iron-dextran is not excreted in urine or in bile.
Because dextran is antigenic, anaphylactic reaction are more common.
HOW TO ADMINISTER
a. INTRAMUSCULAR:
oInjection is given deeply in gluteal region using Z track technique(to avoid staining
of skin).
oIron dextran is injected 2ml daily, or on alternate days, or 5ml each side on the same
day.
b. INTRAVENOUS:
oA dose of 2ml containing 100 mg iron is injected per day taking 10 mins for
injection.
oAlt., total calculated dose is diluted in 500 mg of glucose/ saline solution and
infused i.v. over 6-8 hrs under constant observation.
 ADR
 LOCAL: Pain @site (i/m), skin pigmentation, sterile abscess(esp. in old, debilitated pts.)

 SYSTEMIC: Fever, Headache, Joint pain,

Flushing, Palpitations, Chest pain, Dyspnoea
LN enlargement
 Anaphylactoid rxn w/ Vascular collapse & Death(occasionally)
FERROUS-SUCROSE
 HMW complex- Fe hydroxide + Sucrose

 On i/v, taken up by RE cells, Fe dissociates, and utilized

 Safer than Fe dextran

 Dose- 100mg(upto 200mg) i/v for 5 mins- once daily to once weekly
(till Total Calculated dose is administered).

i/v infusion- not possible

i/m or s/c-not possible(as highly alkaline)

 Hypersensitivity + other s/e – milder
 Particularly indicated- Anemia in Kidney d/s
 Oral Fe should Not be given concurrently and till 5 days after last inj.
 FERRIC CARBOXYMALTOSE
 Here, Fe(OH)3 core stabilized by Carbohydrate shell.
 M.O.A-
• Rapidly taken by RE cells(esp. in BM-upto 80%),
• Fe released and delivered to target cells.
Dose-
• 100mg i/v Daily or
• Upto 1000mg diluted with 100mg saline(not glucose) i/v infusion –15 mins/more-wkly
• No i/m

Rapid in Fe levels in anemic pts in trials.

ADR: Mild Headache, Nausea, Abdominal pain, Hypotension, flushing, Chest pain
Anaphylaxis-rare
Not used in children<14yrs
IRON SORBITOL
 Given i.m
 Iron sorbitol is absorbed directly into the bloodstream as well as via the lymphatic
system. 
Sixty-six percent of the intramuscular injection is absorbed within 3 hours. 
 30% is eliminated through urine in 24 hours.
C/I in Renal failure patients
IRON ISOMALTOSIDE-1000
 Latest injectable Fe formulation; Consists of Fe tightly bound in a matrix of Isomaltoside-1000(oligosacch with
MW 1000)

M.O.A- after i/v injection, Fe rapidly taken up by RE cells, slowly released for use by erythropoietic cells; tight
binding w/n matrix-release very little labile Fe(toxicity)

 Thus, admin. of single dose 1-2g i/v for 15-30 min- full Fe deficit corrected by a single short period i/v infusion

 Or 100-200mg i/v for 5 min daily

 Plasma t1/2= 20-32 hrs; Only 1% excreted by urine

High efficacy, Low immunogenicity with favourable safety profile

S/E- Nausea, Epigastric pain, Abdominal cramps, Constipation/Diarrhea

May be concluded that Ferric carboxy maltose and Iron
isomaltoside1000 are the two most convenient and safest i/v Iron
formulations.
 USES
1. Fe Deficiency Anaemia
 Most imp. Indication for Fe therapy

 Fe- normally orally, parenteral only for special circumstances.

 Rise in Hb level by 0.5 to 1 g/dl per wk- optimum response to Fe therapy.

 Faster in the beginning & when Anemia is severe

 Later, rate of in Hb% declines.

 With therapy, normal Hb is attained gen by 1-3 mnths depends on severity of anemia)

 Treatment should be continued 3-6 months even after correction of cause of deficiency, to correct
anemia and replenish stores

 PROPHYLAXIS: Later ½ of pregnancy, Infancy, c/c Illness, Menorrhagia, after a/c blood loss
STAGES OF IRON DEFICIENCY
2. Megaloblastic Anemia
 Brisk Hematopoiesis following vit. B12/Folate therapy-can unmask Fe
deficiency.

 Fe status of such pts. should be evaluated, and Fe given accordingly

ACUTE IRON POISONING

 Mostly in Infants, Children; v. rare in Adults.

10-20 Fe tablets or its equivalent of liquid prep(>60mg/kg Fe) can cause serious toxicity

Manifestations: Vomiting, Abd. Pain, Hematemesis, Diarrhea, Cyanosis, Dehydration,

Acidosis, Convulsions,-finally Shock, CV collapse, Death

 Few cases- death occurs early(w/n 6 hrs.), but typically delayed to 12-36 hrs. w/ apparent
improvement in the intervening period

 Pathological lesion- Hemorrhage, Inflammation in gut-which may progress to Necrotizing

enteritis, Hepatic necrosis, Brain damage
TREATMENT(should be prompt)
 To prevent further absorption from gut
1. Induce vomiting/gastric lavage w/ NaHCO3 – to render Fe insoluble
2. Give egg yolk &milk orally- to complex Fe

 To bind and remove Fe already absorbed

oDOC- Desferrioxamine(Fe chelating agent)-i/m or i/v
oi/m(preferred)- 0.5-1g(50mg/kg) repeated 4-12 hrly
oi/v(if shock is present) -10-15mg/kg/hr; max. 75mg/kg in a day till serum Fe falls below
300microg/dl
oEarly therapy w/ Desferrioxamine- reduced mortality drastically in Fe toxicity
oAlt, DTPA/ Calcium edetate used; BAL- C/I (as its Fe chelate is also toxic)
Supportive Measures-
• Fluid, Electrolyte balance maintained
• Acidosis-corrected by appropriate i/v infusion
• Respiration & B.P- may need support
• Diazepam i/v to control convulsions