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A Textbook of Clinical Pharmacology and Therapeutics

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390 ANAEMIA AND OTHER HAEMATOLOGICAL DISORDERS<br />

Iron absorption<br />

from gut<br />

Red cell<br />

precursors in<br />

bone marrow<br />

<strong>and</strong> is normally 54–80 μmol/L. Transferrin saturation (i.e.<br />

plasma iron divided by TIBC) is normally 20–50% <strong>and</strong> provides<br />

a useful index <strong>of</strong> iron status. In iron-deficiency states,<br />

TIBC rises in addition to the fall in plasma iron, <strong>and</strong> when<br />

transferrin saturation falls to less than 16%, erythropoiesis<br />

starts to decline. The cause <strong>of</strong> iron deficiency is most <strong>of</strong>ten<br />

multifactorial, e.g. poor diet combined with excessive<br />

dem<strong>and</strong>s on stores (pregnancy, chronic blood loss, lactation),<br />

reduced stores (premature birth) or defective absorption<br />

(achlorhydria, surgery to the gastro-intestinal tract). Although<br />

treatment <strong>of</strong> iron deficiency is straightforward, its cause<br />

should be determined so that the underlying condition can be<br />

treated. Iron-deficiency anaemia in men or post-menopausal<br />

women is seldom due solely to dietary deficiency, <strong>and</strong> a thorough<br />

search for other causes (notably colon cancer) should be<br />

undertaken.<br />

IRON PREPARATIONS<br />

Ferritin in<br />

liver cells<br />

Transferrin<br />

Red cells in<br />

circulation<br />

Figure 49.1: Iron metabolism.<br />

Other cell systems<br />

(e.g. myoglobin,<br />

cytochromes)<br />

Red cell breakdown<br />

Iron resorption by<br />

macrophages<br />

ORAL IRON<br />

Most patients with iron deficiency respond to simple oral iron<br />

preparations. Treatment is continued for 3–6 months after<br />

Table 49.1: Ferrous iron content <strong>and</strong> relative cost <strong>of</strong> available iron formulations<br />

haemoglobin concentrations enter the normal range, in order<br />

to replace iron stores. Failure to respond may be due to:<br />

• wrong diagnosis;<br />

• non-compliance with therapy;<br />

• continued blood loss;<br />

• malabsorption (e.g. coeliac disease, post-gastrectomy).<br />

There are too many iron-containing preparations available,<br />

many containing vitamins as well as iron. None <strong>of</strong> these combinations<br />

carries an advantage over iron salts alone, except for<br />

those containing folic acid, which are used prophylactically in<br />

pregnancy. Treatment should start with a simple preparation<br />

such as ferrous sulphate, ferrous fumarate or ferrous gluconate.<br />

Examples <strong>of</strong> commonly available iron preparations are<br />

listed in Table 49.1.<br />

Adverse effects<br />

Gastro-intestinal side effects, including nausea, heartburn, constipation<br />

or diarrhoea, are common. Patients with ulcerative<br />

colitis <strong>and</strong> those with colostomies suffer particularly severely<br />

from these side effects. No one preparation is universally better<br />

tolerated than any other, but individual patients <strong>of</strong>ten find<br />

that one salt suits them better than another. Ferrous sulphate is<br />

least expensive, but if it is not tolerated it is worth trying an<br />

organic salt, e.g. fumarate. Although iron is best absorbed in the<br />

fasting state, gastric irritation is reduced if it is taken after food.<br />

Accidental overdose with iron is not uncommon in young<br />

children <strong>and</strong> can be extremely serious, with gastro-intestinal<br />

haemorrage, cardiovascular collapse, hepatic <strong>and</strong> neurotoxicity.<br />

Desferrioxamine (an iron-chelating agent) is administered to<br />

treat it (Chapter 54).<br />

IRON PREPARATIONS FOR CHILDREN<br />

Sugar-free liquid preparations that do not stain the teeth<br />

should be used in paediatrics (e.g. sodium iron edetate). The<br />

dose is calculated in terms <strong>of</strong> the amount <strong>of</strong> elemental iron.<br />

PARENTERAL IRON<br />

Oral iron is effective, easily administered <strong>and</strong> cheap. Parenteral<br />

iron (formulated with sorbitol <strong>and</strong> citric acid) is also effective,<br />

but can cause anaphylactoid reactions <strong>and</strong> is expensive. The<br />

rate <strong>of</strong> rise in haemoglobin concentration is no faster than after<br />

oral iron, because the rate-limiting factor is the capacity <strong>of</strong> the<br />

Iron formulation Ferrous iron content Approximate ratio <strong>of</strong> cost<br />

in one unit dose for one unit dose<br />

Ferrous sulphate 60 mg 1<br />

Ferrous fumarate 65 mg 2<br />

Ferrous gluconate 35 mg 2.6<br />

Ferrous succinate 35 mg 3<br />

Sodium ironedetate 27.5–55 mg 6<br />

Polysaccharide iron complex 50–100 mg 11

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