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IRON SALTS
Adequate iron intake is necessary for normal erythropoiesis, as well as for numerous
iron containing proteins. Iron deficiency anemia is the most frequent type of anemia. In the
absence of iron, eythrocytes will be small, with insufficient hemoglobin, the microcytic
hypochromic anemia. Iron stores will be emptied, serum ferritin and iron levels decrease,
the total capacity of binding iron increases. Red blood cell indices will be low.
Iron deficiency is a result of a:
● Restrictive diet, in vegetarians.
● Inadequate absorption, after gastrectomy or in severe malabsorption syndrome.
● Increased need of iron, during pregnancy or rapid growth.
● Acute or chronic blood loss, menometrorrhagias or upper digestive bleeding.
Hepcidin is a peptide hormone, synthesized in the liver, with a regulatory role in iron
metabolism. It inhibits the iron transportation through binding to ferroportin, localized on
the basolateral surface of the enterocytes and the plasmatic membrane of
reticuloendothelial cells (macrophages), with the impounding of iron inside the cell.
Intestinal iron absorption will be decreased and iron can not leave the macrophages, their
main storage place. The increased activity of hepcidin is partially responsible for the anemia
in chronic inflammation.
Classification
Regarding the route of administration, iron salts are classified in:
● Iron administered orally
o FERROUS SULPHATE – o FERROUS FUMARATE
first line o FERROUS GLUTAMATE
o FERROUS GLUCONATE o FERROCHOLINATE
● Iron administered parenterally
o IRON DEXTRAN
Pharmacokinetics
● Iron is an essential element, that can be found in food like meat (especially liver,
heart), wheat germs, eggs, dried beans and fruits. The daily diet should contain 10-20
mg of iron. The total amount in the body is 4-5 g, with the following distribution: 65-
70% in hemoglobin, 4% in myoglobin, 1% in hem compounds and 15-30% in deposits
as ferritin or hemosiderin in the liver, spleen, intestinal mucosa and bone marrow.
● Iron has a medium absorption of 10-20% from the diet (Fe 2+ - ferrous form is better
absorbed) in the duodenum and proximal jejunum, through active transport (see
figure). In the enterocyte it is transformed to Fe 3+ (ferric iron). The absorption rate
increases in: pregnancy, menstruation period, growth and anemia. Hem iron from
hemoglobin in meat and myoglobin can be absorbed unchanged. On the other hand,
iron from vegetables or cereals is less disposable for absorption. Ascorbic acid
facilitates the GI absorption, antacids reduce it.
● Ferric iron binds to transferrin, a beta1 glycoprotein, in plasma and is distributed to
the tissues.
● Ferritin and hemosiderin are the storage forms from the macrophages in the liver,
spleen and bones. Ferritin levels (the normal value is 20-300 mmol/l) are important
to establish the iron stores in the body.
● The daily elimination of iron is 1 mg. 2/3 of the iron is excreted from the GI tract as
extravasated red cells, iron in bile and iron in exfoliated mucosal cells. 1/3 includes
iron in desquamated skin and in the urine.
Mechanism of action
● At tissue level, the transferrin-iron complex internalizes and releases iron in the
cytoplasm.
● Iron is a constituent of hemoglobin and myoglobin, is important in the metabolism of
cathecolamines, the normal functioning of neutrophils, epithelial cell nutrition and
has a catalytic role in the cell respiration.
● The normal daily requirements of iron are 1-1.4 mg, higher in the last two trimesters
of pregnancy (5-6 mg/day).
Mechanism of action
● Vitamin B12 is required for DNA synthesis and effective erythropoiesis.
● Animal products are high in vitamin B12. The daily requirement is 3-5 μg.
Pharmacokinetics
● Vitamin B12 is rapidly absorbed from IM and SC sites of injection. GI absorption
depends on the presence of intrinsic factor, bile and sodium bicarbonate. Vitamin B 12
is bound to the intrinsic factor in the stomach, separation and absorption occurs in
the terminal ileum.
● Causes of vitamin B12 deficiencies are: achlorhydria, decreased secretion of intrinsic
factor by parietal cells (in gastric atrophy, gastric surgery), antibodies to parietal cells
or intrinsic factor complex, pancreatic disorders, bacterial overgrowth, intestinal
parasites, sprue or intestinal surgery.
● Absorbed vitamin B12 binds to a specific binding protein, transcobalamin II, which
transports this vitamin to the tissues. The liver is the main vitamin B 12 storage organ.
● Vitamin B12 is renally eliminated.
Indications
● Pernicious anemia (megaloblastic erythropoiesis, paresthesias, unsteadiness,
decreased deep tendon reflexes, confusion, loss of memory, even psychosis). In
pernicious anemia, initial treatment requires regular daily injections of 100-1.000μg,
two weeks, continued with 100 μg/month for life. If the GI function is normal, oral
administration may be indicated.
● Other macrocytic megaloblastic anemias.
Adverse effects
● Fever, chills
● Flushing
● Nausea, diarrhea
FOLIC ACID
Mechanism of action
● Folate is required for DNA synthesis and effective erythropoiesis.
● Foods rich in folates: green vegetables, liver and some fruits. Daily requirement: 400
μg; during pregnancy or lactation: 500-600 μg/day.
Pharmacokinetics
● Folic acid polyglutamates from food sources are enzymatically hydrolyzed in the GI
tract to monoglutamates prior to absorption in the proximal small intestine.
● Folic acid is converted in the liver and plasma to its metabolically active form
tetrahydrofolic acid, and distributed to the tissues. Folate is stored within cells as
polyglutamates. The liver contains about a half of total folate stores.
Indications
● Macrocytic and megaloblastic anemias caused by folate deficiency (alcoholism,
patients on total parenteral nutrition, sprue tropical or nontropical).
● Prophylaxis of neural tube defects in pregnancy (spina bifida, encephaloceles,
anencephaly).
Drug interactions
● Drugs that inhibit dihydrofolate reductase: Methotrexate, Trimethoprim;
● Drugs that interfere with the absorption and storage of folate in tissues:
anticonvulsants, oral contraceptives.
Therapeutic notes
● The use of Folic acid in patients with vitamin B 12 deficiency may result in hematologic
improvement, while neurologic damages progress and become irreversible.
ERYTHROPOIETIN