2. Objectives
• Understand the concept of hematinics and their
importance in clinical medicine.
• Explore the mechanism of action for different types of
hematinics.
• Discuss the pharmacokinetics and
pharmacodynamics of hematinics.
• Highlight clinical applications, indications, and
potential side effects.
3. Haematinics
• treat or prevent disorders characterized by
reduced red blood cell (RBC) production or
increased RBC destruction
• replenish the body's iron, vitamin B12, and
folic acid stores, which are vital for RBC
synthesis
9. Iron Absorption
• duodenum and proximal jejunum of the
small intestine
• Dietary iron exists in two forms
1. heme iron (found in animal-derived foods)
2. non-heme iron (found in plant-based foods
and supplements)
10. • Heme iron is more readily absorbed than non-
heme iron due to its complex with heme carrier
protein 1 (HCP1).
• Iron absorption is regulated by the body's iron
status. In times of deficiency, absorption
increases, while in excess, it decreases
11. Factors facilitating iron absorption
• Acid: by favoring dissolution and reduction of ferric
iron
• Reducing substances: ascorbic acid, amino acids
containing SH radical. These agents reduce ferric iron
and form absorbable complexes
• Meat: by increasing HCI secretion and providing
haeme iron.
12. Factors impeding iron absorption
• Alkalis (antacids) render iron insoluble, oppose its
reduction
• Phosphates (rich in egg yolk)
• Phytates (in maize, wheat)
• Tetracyclines
• Presence of other foods in the stomach.
13. Iron Distribution and Metabolism
• Iron is transported through the bloodstream bound to
TRANSFERRIN, a plasma protein that serves as the
major iron carrier.
• Transferrin transports iron to various tissues and organs,
including the liver, bone marrow, and muscles.
• Within cells, iron is stored in the form of FERRITIN, a
protein complex that can hold thousands of iron atoms
14. • Ferritin acts as an iron reservoir, releasing iron when
needed for cellular processes.
• HEPCIDIN, a hormone produced by the liver, regulates
iron metabolism by controlling the release of iron from
enterocytes, macrophages, and hepatocytes.
• Hepcidin binds to the iron exporter protein Ferroportin,
leading to its degradation and inhibiting iron export
15. Iron Transport
• Iron is transported from the intestinal lumen into
enterocytes by the divalent metal transporter 1
(DMT1).
• Once inside enterocytes, iron can follow two
pathways: storage or export.
• Iron destined for storage is converted into ferritin and
stored in enterocytes as ferric iron (Fe3+).
16. • Iron intended for export is transported across the
basolateral membrane of enterocytes by
FERROPORTIN, the sole known iron exporter.
• Ferroportin allows iron to enter the bloodstream,
where it binds to transferrin for distribution to other
tissues
17. Iron Metabolism and Regulation
• Iron metabolism is tightly regulated to maintain
homeostasis.
• Hepcidin plays a central role in iron regulation by
inhibiting ferroportin and reducing iron export.
• Hepcidin synthesis is influenced by factors such as
iron stores, erythropoietic activity, and inflammatory
signals.
18. • In conditions of iron deficiency, hepcidin levels
decrease, promoting iron absorption and release from
storage sites.
• In contrast, iron overload, inflammation, or certain
diseases can increase hepcidin levels, leading to
reduced iron absorption and sequestration within
cells
19. Iron Excretion
• Not actively excreted from the body under normal
circumstances.
• Small amounts are lost through shedding of epithelial
cells, sweat, urine, and feces.
• During menstruation or bleeding, significant iron loss
occurs, and excretion via blood loss helps to regulate
iron levels
21. Oral iron preparations
• Preferred route
• Dissociable ferrous salts: inexpensive, increased iron
content, better absorbed
e.g. Ferrous salts- cheapest and most widely used
• Mild adverse effects- nausea, upper abdominal pain,
diarrhoea and constipation
22. • Ferrous sulphate (hydrated salt 20% iron , dried salt
32% iron)
• Ferrous gluconate ( 12% iron)
• Ferrous fumarate (33% iron)
• Colloidal ferric hydroxide (50% iron)
• Carbonyl iron
23. Adverse effects of oral iron
• Related to the elemental iron content.
• Epigastric pain, heartburn, nausea, vomiting,
bloating, staining of teeth, metallic taste, colic
• Tolerance to therapy: low dose optimum dose.
• Constipation >> diarrhea
24. Parenteral iron preparation
Indications
• iron malabsorption (e.g., sprue, short-bowel
syndrome)
• severe oral iron intolerance
• routine supplement to total parenteral nutrition
• patients who are receiving erythropoietin
25. • Iron –dextran
• Ferrous-sucrose
• Sodium Ferric Gluconate
• Ferric carboxymaltose
• Iron isomaltoside-1000
26. • Iron requirement (mg) = 4.4 x body weight (kg) x Hb
deficit (g/dl)
• This formula includes iron needed for replenishment
of stores
29. • infants and children (1-2 years), very rare in adults
• As little as 1–2 g of iron may cause death, but 2–10 g usually
is ingested in fatal cases.
• Signs and symptoms include : abdominal pain, diarrhea, or
vomiting of brown or bloody stomach contents containing
pills.
• Pallor or cyanosis, lassitude, drowsiness, hyperventilation
due to acidosis, and cardiovascular collapse
• The corrosive injury to the stomach may result in pyloric
stenosis or gastric scarring
30. Management
To prevent further absorption of iron from gut
• Induce vomiting or perform gastric lavage with
sodium bicarbonate solution- to render iron insoluble
• Give egg yolk and milk orally: to complex iron
31. To bind and remove iron already absorbed
• Deferoxamine
plasma concentration of iron is greater than the
total iron-binding capacity
• Deferiprone and Deferasirox
FDA approved for treatment of patients with
thalassemia who have iron overload
33. • Erythropoietin (EPO) is a glycoprotein hormone
produced mainly by the kidneys.
• In response to decreased oxygen levels in the blood,
specialized cells in the kidneys called peritubular
fibroblasts secrete erythropoietin.
• A small amount is also produced by the liver.
• Required for erythropoiesis.
• Deficiency leads to anaemia.
34. Mechanism of action
• EPO acts by binding to erythropoietin receptors on
erythroid progenitor cells in the bone marrow.
• Stimulates the proliferation and differentiation of
these cells, leading to increased red blood cell
production.
36. EPO preparations
• Recombinant Human Erythropoietin (rHuEPO):
e.g. Epoetin alfa and Epoetin beta
most commonly used
• Darbepoetin alfa:
longer half-life.
requires less frequent dosing compared to
rHuEPO
37. Indications for Erythropoietin
• Anemia of Chronic Kidney Disease (CKD)
• Chemotherapy-Induced Anemia
• Anemia in HIV Patients
• Anemia of prematurity
• Myelodysplasia
• Preoperative increased blood production for
autologous transfusion during surgery.
• Performance enhancing drug by athletes (doping
agent)
38. Adverse effects of EPO therapy
• Hypertension: EPO therapy can increase blood
pressure, requiring careful monitoring and
management.
• Thromboembolic Events: EPO increases the risk of
blood clot formation, including deep vein thrombosis
and pulmonary embolism.
• Pure Red Cell Aplasia (PRCA): Rarely, long-term use
of EPO can lead to PRCA, characterized by a severe
decrease in red blood cell production.