Hematinic I

1. Aditia Retno Fitri
Department of Pharmacology
Faculty of Medicine Diponegoro University
Indonesia

2. Overview
Hematinic Agents
Iron
Folic Acid and Vitamine B12
Haemopoetic Growth Factors

4. http://www.theironfiles.co.uk/Sickle-cell/General/SCDBlood.html

5. http://www.theironfiles.co.uk/Sickle-cell/General/SCDBlood.html

6. 4 globin + 1 haem.
Haem
consists of a tetrapyrrole
porphyrin ring containing
ferrous (Fe
2+
) iron.
Each haem group can carry 1
oxygen molecule
bound reversibly to Fe
2+
and to a
histidine residue in the globin
chain  basis of oxygen
transport.

7. Definition: ↓ [Hb] in blood &/ RBC per age, sex and
geographical location.
Normal Hb:
14g to 16g /dl in Male
13g to 15g /dl in Female
Acute: fatigue  chronic: asymptomatic.
Classification based on indices of red cell are:
hypochromic, microcytic anaemia
macrocytic anaemia
normochromic normocytic anaemia
mixed pictures.

9. BALANC
E
OUTPUT
MACHINE
INPUT

10. <<<< INPUT:
Nutritional
deficiency
IMBALANC
E
BROKEN MACHINE
-- Synthesis <<
-- Chronic disease
>>>OUTPUT:
Bleeding
Haemolysis

11. <<<< INPUT:
Nutritional
deficiency
IMBALANC
E
BROKEN MACHINE
-- Synthesis <<
-- Chronic disease
>>>OUTPUT:
Bleeding
Haemolysis
FIX THE UNDERLYING
CAUSES!!

12. ↓↓↓↓ FORMATION
1. Nutritional
Iron Deficiency
Folic Acid/ Vit B
12 Deficiency
Protein Deficiency
2. Decreased Synthesis
Aplastic Anaemia
Replacement of BM (e.g.
Leukaemia)
Thalassaemia
3. Chronic Disorder
Kidney Disease
Advanced Malignancy
Chronic Liver Disease

↑↑↑↑
DESTRUCTION
1. Post Haemorrhage
Acute & chronicBlood Loss
2. Excessive
Haemolysis
Intracellular Defect
(Defective RBC)
▪Thalassaemia
▪Haemoglobinopathies
▪Sickle Cell Anaemia
Extracellular Defect
▪Rh Incompatibility
▪Auto Immune Haemolytic
Anaemia
▪Certain Snake Venom

14. Hematinics are drugs used to stimulate the
formation of red blood cells.
Used primarily in the treatment of anemia
 Example:
Iron
Folic Acid
Vitamin B12

16. Basic Pharmacology
Pharmacokinetic
Absorption
Pharmacodynamic
Indication
Drug Interaction
Side Effect

17. Important properties :
several oxidation states
form stable coordination complexes
Fe + protoporfirin  Heme
Heme + globin  Hemoglobin
Hemoglobin binds O2 & provides O2 delivery
Fe deficiency  microcytic hypochromic anemia
Body content of iron:
Essential: myoglobin, Hb, enzym, transferrin  not
available for haemoglobin synthesis
Storage: Ferritin, hemosiderin Hb synthesis

20. P
H
A
R
M
A
C
O
K
I
N
E
T
I
C
S

21. Daily diet : 10–15 mg  absorbption 5–10%
Location : duodenum and proximal jejunum
Heme iron  directly absorbed
Nonheme iron  reduced to ferrous (Fe
2+
)  absorbed
Iron crosses the luminal membrane by active transport of ferrous
iron and absorption of iron complexed with heme
DMT1  transporter
absorbed iron can be actively transported into the blood by
ferroportin and oxidized to ferric iron (Fe
3+
)
Excess iron can be stored in intestinal epithelial cells as ferritin

22. Iron is transported in the plasma bound to transferrin
Transferrin-iron complex receptor-mediated
endocytosis enters maturing erythroid cells
Endosomes: ferric  ferrous  transported by DMT1 
hemoglobin synthesis or stored as ferritin.
The transferrin-transferrin receptor complex is recycled
to the plasma membrane, where the transferrin
dissociates and returns to the plasma.

23. Storage :
in intestinal mucosal cells: as ferritin
 in macrophages in the liver, spleen, and bone, and in
parenchymal liver cells.
Apoferritin synthesis is regulated by the levels of
free iron.
Ferritin present in serum is in equilibrium with
storage ferritin in reticuloendothelial tissues 
the serum ferritin level can be used to estimate
total body iron stores.

24. no mechanism for excretion
Small amounts are lost in the feces by :
exfoliation of intestinal mucosal cells
trace amounts are excreted in bile, urine, and
sweat
 no more than 1 mg of iron per day.
regulation of iron balance : absorption and
storage

25. http://izzrawda.wordpress.com/2009/03/16/do-you-have-anemia/

26. The daily requirement of iron
Male : 1mg / day
Female
▪2mg / day
▪3mg / day (during pregnancy and lactation)
Iron deficiency anaemia can occur under the following four
conditions:
Less Intake of Fe, Vitamins and Protein
Diminished Absorption
Increased Loss
Excessive Demand

28. Basically: Iron deficiency
Application:
Iron deficiency due to dietary lack or to chronic
blood loss.
Pregnancy: TM2
GIT abnormality: malabsorption
Premature baby
Early treatment of pernicious anemia

29. Oral:
ferrous sulfate, ferrous succinate, ferrous gluconate and
ferrous fumarate.
SE: GIT upset, blackened stool, teeth stain
Form: tablet, liquid, sustained-release
Parenteral iron
Indication: not able to absorb oral iron
Prep
Deep IM: iron-dextran (50 mg Fe/mL) or iron-sorbitol
 precaution: local reaction, anaphylaxis
Slow IV: iron dextran, sodium ferric gluconate complex, iron
sucrose
Precaution: risk of anaphylacsis!!!
Oral iron should not be given 24 h before i.m. begin and for 5
days after the last i.v. injection;

31. Therapeutic dose:
3-6 mg/Kg/day of elemental ironInduces an ↑Hb of
0.25-0.4 g/dl per day or 1%/day rise in hematocrit.
Adequate response:
↑ Hb of 2 g/dl after 3 weeks of tx
Failure of response
after 2 weeks of oral iron requires reevaluation for ongoing
blood losses,infection,poor compliance or other causes of
microcytic anaemia.
Priority: oral preparation.

32. Iron chelates in the gut with tetracyclines,
penicillamine, methyldopa, levodopa,
carbidopa, ciprofloxacin, norfloxacin and
ofloxacin;
it also forms stable complexes with thyroxine,
captopril and biphosphonates.
Ingestion should be separated by 3 hours.
↑absorption: vit C
↓absorption: desferrioxamine, tea (tannins) ,
Ca, Zn, and bran

33. chronic infection
in haemolytic anaemias unless there is also
haemoglobinuria
increased erythropoiesis associated with chronic
haemolytic states stimulates increased iron
absorption and adding to the iron load may cause
haemosiderosis.

34. Dose related, include nausea, abdominal cramps and diarrhoea.
overcome : ↓dose or by taking the tablets after or with meals
Acute iron toxicity
Ingestion of large quantities of iron salts.
Result: severe necrotising gastritis with vomiting,
haemorrhage and diarrhoea  collapse
 Treatment : gastric lavage with NaHCO3, iron chelating
agent, and treatment of causes.
Chronic iron toxicity
Caused by conditions other than ingestion of iron salts,
Cause pancreatic damage and leading to diabetes.

37. Used for treatment of iron toxicity
Desferrioxamine(Desferal) (t1/2 6 h).
▪not absorbed from the gut but is nonetheless given
intragastrically following acute overdose (to bind iron in the
bowel lumen and prevent its absorption) as well as IM and IV
▪In severe poisoning: slow IV too fast: hypotension
▪forms a complex with ferric iron, excreted in the urine.
Deferiprone
▪orally absorbed
▪to treat iron overload in patients with thalassaemia major, in
whom desferrioxamine is CI.
▪careful monitoring : Agranulocytosis and other blood
dsyscrasias

38. Present as haemoglobin; myoglobin, cytochromes and other enzymes.
Absorption: Ferric iron (Fe
3+
)  ferrous iron (Fe
2+
)
active transport into mucosal cells in jejunum and upper ileum
transported into plasma and/or stored intracellularly as ferritin.
Iron loss occurs mainly by sloughing of ferritin-containing mucosal cells;
iron is not excreted in the urine.
Iron in plasma is bound to transferrin, and most is used for erythropoiesis.
Some is stored as ferritin in other tissues. Iron from time-expired erythrocytes
enters the plasma for re-use.
The main therapeutic preparation is ferrous sulfate.
Unwanted effects include gastrointestinal disturbances. Severe toxic effects
occur if large doses are ingested; these can be countered by desferrioxamine,
an iron chelator.

40. Basic and Clinical Pharmacology 11th Ed,
Katzung
Pharmacology Rang et al 5th Edition
Goodman & Gilman’s The Pharmacological
Basis of Therapeutics, 11th ed.
Color atlas of pharmacology
Clinical Pharmacology, 9th Ed
USMLE Pharmacology Recall
Pharmacology for the health care profession