Clinical Pharmacology and Therapeutics

390 ANAEMIA AND OTHER HAEMATOLOGICAL DISORDERS
Iron absorption
from gut
Ferritin in
liver cells
Transferrin
Other cell systems
(e.g. myoglobin,
cytochromes)
haemoglobin concentrations enter the normal range, in order
to replace iron stores. Failure to respond may be due to:
• wrong diagnosis;
• non-compliance with therapy;
• continued blood loss;
• malabsorption (e.g. coeliac disease, post-gastrectomy).
Red cell
precursors in
bone marrow
Red cells in
circulation
Figure 49.1: Iron metabolism.
and is normally 54–80 μmol/L. Transferrin saturation (i.e.
plasma iron divided by TIBC) is normally 20–50% and provides
a useful index of iron status. In iron-deficiency states,
TIBC rises in addition to the fall in plasma iron, and when
transferrin saturation falls to less than 16%, erythropoiesis
starts to decline. The cause of iron deficiency is most often
multifactorial, e.g. poor diet combined with excessive
demands on stores (pregnancy, chronic blood loss, lactation),
reduced stores (premature birth) or defective absorption
(achlorhydria, surgery to the gastro-intestinal tract). Although
treatment of iron deficiency is straightforward, its cause
should be determined so that the underlying condition can be
treated. Iron-deficiency anaemia in men or post-menopausal
women is seldom due solely to dietary deficiency, and a thorough
search for other causes (notably colon cancer) should be
undertaken.
IRON PREPARATIONS
Red cell breakdown
Iron resorption by
macrophages
ORAL IRON
Most patients with iron deficiency respond to simple oral iron
preparations. Treatment is continued for 3–6 months after
There are too many iron-containing preparations available,
many containing vitamins as well as iron. None of these combinations
carries an advantage over iron salts alone, except for
those containing folic acid, which are used prophylactically in
pregnancy. Treatment should start with a simple preparation
such as ferrous sulphate, ferrous fumarate or ferrous gluconate.
Examples of commonly available iron preparations are
listed in Table 49.1.
Adverse effects
Gastro-intestinal side effects, including nausea, heartburn, constipation
or diarrhoea, are common. Patients with ulcerative
colitis and those with colostomies suffer particularly severely
from these side effects. No one preparation is universally better
tolerated than any other, but individual patients often find
that one salt suits them better than another. Ferrous sulphate is
least expensive, but if it is not tolerated it is worth trying an
organic salt, e.g. fumarate. Although iron is best absorbed in the
fasting state, gastric irritation is reduced if it is taken after food.
Accidental overdose with iron is not uncommon in young
children and can be extremely serious, with gastro-intestinal
haemorrage, cardiovascular collapse, hepatic and neurotoxicity.
Desferrioxamine (an iron-chelating agent) is administered to
treat it (Chapter 54).
IRON PREPARATIONS FOR CHILDREN
Sugar-free liquid preparations that do not stain the teeth
should be used in paediatrics (e.g. sodium iron edetate). The
dose is calculated in terms of the amount of elemental iron.
PARENTERAL IRON
Oral iron is effective, easily administered and cheap. Parenteral
iron (formulated with sorbitol and citric acid) is also effective,
but can cause anaphylactoid reactions and is expensive. The
rate of rise in haemoglobin concentration is no faster than after
oral iron, because the rate-limiting factor is the capacity of the
Table 49.1: Ferrous iron content and relative cost of available iron formulations
Iron formulation Ferrous iron content Approximate ratio of cost
in one unit dose
for one unit dose
Ferrous sulphate 60 mg 1
Ferrous fumarate 65 mg 2
Ferrous gluconate 35 mg 2.6
Ferrous succinate 35 mg 3
Sodium ironedetate 27.5–55 mg 6
Polysaccharide iron complex 50–100 mg 11