Iron (Load Physiology and Formulations)

Pharmacokinetics

Mechanism of absorption and systemic homeostasis

Dietary inorganic iron exists mainly in the insoluble ferric form (Fe³⁺). In the apical membrane of the duodenal enterocyte, the metaloreductase duodenal cytochrome b (Dcytb) reduces iron to its soluble ferrous form (Fe²⁺), allowing its uptake by the divalent metal cotransporter 1 (DMT1). Cellular iron follows two pathways:

1. Storage: It is sequestered intracellularly within the hollow spherical protein ferritin in the form of inert ferric hydroxide.
2. Export: It is transferred to the general circulation through the basolateral protein ferroportin. After its release, the ferroxidase hephaestin reoxidizes it to Fe³⁺, allowing its specific binding to the plasma transport glycoprotein transferrin.

The control of iron transit is regulated by the liver hormone hepcidin:

In states of iron deficiency or overload, or in the presence of inflammatory cytokines (such as IL-6), the liver increases hepcidin production. This binds to the basolateral ferroportin of enterocytes and macrophages, inducing their cellular degradation, selectively blocking the export of iron to the blood and trapping it in tissue deposits.

Oral and Intravenous Iron Formulations

Replenishment of deposits requires proper selection of the route and type of salt:

• Ferrous Sulfate (Oral): Low-cost classic salt with 20% elemental iron. It has a high incidence of gastrointestinal adverse effects (epigastralgia, constipation, dark stools) due to unabsorbed free iron that induces tissue lipid peroxidation.
• Carboxymaltose Iron (Intravenous): Complex of colloidal polynuclear iron core covered by a carbohydrate corona that allows controlled release directly into macrophages without releasing toxic free iron to the plasma. Allows rapid administration of large therapeutic doses (up to 1000 mg in a single infusion).

Security

Clinical Indications, ADR and Toxicity

Indicated for the treatment of hypochromic microcytic iron deficiency anemia, chronic blood loss and support during pregnancy.

Adverse reactions to oral salts include nausea, cramping pain, severe constipation, and transient staining of teeth in children's liquid solutions. Intravenous iron can induce severe transient hypophosphatemia due to stimulation mediated by the renal hormone FGF-23, manifesting itself as extreme weakness.

Acute childhood iron overdose poisoning is a medical emergency that causes gastrointestinal hemorrhagic necrosis, cardiovascular collapse, and severe metabolic acidosis. It is treated by immediate gastric lavage and specific intravenous chelation with deferoxamine.