Drugs for Anemia

Objectives

 On completion of session you will be able to:

 List the drugs used in the treatment of anemia.

Explain different types of iron preparations

Describe the actions, uses, general adverse reactions,

contraindications, precautions, and interactions of
drugs used to treat anemia.

Anti-anemic Drugs

Anemia:
Iron preparations

Vit B12

folic acid

Erythropoietin
Anemia
 Anaemia is defined as a condition of having less than
the normal number of red blood cell or less than the
normal quantity of hemoglobin in the blood

 The oxygen carrying capacity of the blood

decreases


 Classification of Anemia
I. Etiologic Classification

1. Impaired RBC production

2. Excessive destruction

3. Blood loss

II. Morphologic Classification

1. Macrocytic anemia

2. Microcytic hypochromic anemia

3. Normochromic normocytic anemia

 Macrocytic anaemia:

large red cells, few in number

 Normochromic , Normocytic anaemia:

fewer normal sized red cells each with a normal

haemoglobin content
 Impaired RBC Production
1. Abnormal bone marrow
1.1 Aplastic anemia
1.2 Myelophthisis : Myelofibrosis, Leukemia,
Cancer metastasis
2. Essential factors deficiency
2.1 Deficiency anemia : Fe, Vit. B12, Folic acid, etc
2.2 Anemia in renal disease : Erythropoietin
3. Stimulation factor deficiency
3.1 Anemia in chronic disease
3.2 Anemia in hypopituitarism
3.3 Anemia in hypothyroidism
 Iron deficiency anemia
 Result from inadequate iron intake, malabsorption,
blood loss, or an increased requirement, as with
pregnancy
 The major role of iron in mammals is to carry O2 as
part of the heme protein that, in turn, is part of
hemoglobin
 O2 is also bound by a heme protein in muscle,
myoglobin
 Without iron, cells lose their capacity for electron
transport and energy metabolism; in erythroid cells
hemoglobin synthesis is impaired, resulting in anemia
and reduced O2 delivery to tissue.
 is a critical element in iron-containing enzymes,
including the cytochrome system in mitochondria
 Treatment : Iron preparations + treatment of
the cause
Iron preparations and supplements :
 Dietry iron; present in liver , heart , yeast , wheat germ ,
egg yolk , dried beans , cereals , milk and its Products
 Oral preparations :

 Ferrous sulfate 300 mg TID

 Ferrous gluconate 600 mg TID

 Ferrous fumarate 200 mg TID


 Given after meals to avoid gastric irritation

 Treatment with oral iron should be continued for 3-6 months

after correction of the cause of the iron loss.
 This corrects the anemia and replenishes iron stores

 An increase in the reticulocyte count is not observed for at

least 4–7 days after beginning therapy.
 An increase in the Hb level takes even longer, about three wks
Orally administered ferrous sulfate is the treatment of
choice for iron deficiency.
Ferrous salts are absorbed about three times as well as
ferric salts, and the discrepancy increases at high
doses.
Variations in the particular ferrous salt have relatively
little effect on bioavailability.
 Parenteral iron preparations

 Iron dextran (50 mg / ml given im or iv)

 sodium ferric gluconate complex in sucrose

 iron sucrose

 Used if oral iron therapy fails

 A test dose is given ( 0.5 ml ) initially followed by 2 ml

every few days until a total dose 1-2 g Is reached
 Parenteral iron therapy should be used only when clearly
indicated
Common indications are iron malabsorption, severe
intolerance of oral iron, as a routine supplement to
total parenteral nutrition, and in patients who are
receiving erythropoietin.
Parenteral iron also has been given to iron-deficient
patients and pregnant women to create iron stores,
something that would take months to achieve by the
oral route.
 Absorption and metabolism of iron :
 Absorbed well from GIT in the ferrous form .

 Gastric acidity and presence of reducing substances e.g.

Vit.c in the diet favour its absorption
 Meat stimulates iron absorption by stimulating gastric
acid secretion.
 Vegetables decrease iron absorption due to its contents of
phosphates that form unabsorbable complex with iron ,
like magnesium trisilicate
 The ferrous ion enter the mucosal cell (of the duodenum )
and converted into ferric ion
 ferric ion bound to apoferritin (protein) to form ferritin
then ferritin combines with trans - ferrin
 Iron - transferrin complex bind to the receptor - mediated
endocytosis and taken up into the reticuloendothelial cells
to be stored .
 The receptor returns the opoferritin again to the cell
surface to be reused
Iron toxicity :

 Occurs with oral over doses or even with therapeutic

doses given parenterally .
 include ;
 GIT disturbances , haematemesis and acidosis ( occurs with oral iron )
 Headache Constipation Black stools
 Epigastric pain Heartburn Joint pains
 Faintness Tachycardia Collapse
 Hypotension Bronchospasm Chills
 Fever Skin rash Encephalopathy
 Convulsions coma or even death .
 Treatment of acute toxicity :

 Gastric lavage with 1 % sodium bicarbonate ( if given

orally )
 Iron chelating agent (Deferoxamine) either with
gastric tube , im. or iv. (2 mg / 12 hours ).
 Symptomatic treatment for collapse , dehydration ,
acidosis , convulsions .....etc .
 Taken with food to lessen gastric intolerance.
 Eggs, coffee, tea, milk inhibit iron absorption and should be avoided
when taking ferrous sulfate.
 Consider switching patient to newer forms of iron such as ferrous
gluconate and ferrous fumarate which have less GI toxicity.
 drug interactions
 Drugs that increase effects/toxicity of ferrous sulfate: ascorbic acid
(vitamin C).
 Drugs that decrease effects/toxicity of ferrous sulfate: antacids,
cholestyramine, tetracyclines, chloramphenicol.
 Pernicious or Megaloblastic
Hyperchromic Anaemia
 Megaloblastic anemia is characterized by the appearance
of large cells in the bone marrow and blood
 Due to defective maturation of hematopoietic cells

 Result from Folic acid or vitamin B12 deficiency

 Malabsorption, impaired use, chronic infections, and drugs

can lead to folic acid or vitamin B12 deficiency
Vitamin B12 and folic acid are essential to DNA
synthesis.
 Deficiency of either vitamin B12 or folate decreases the
synthesis of methionine, thereby interfering with protein
biosynthesis, a number of methylation reactions, and the
synthesis of polyamines.
The daily nutritional requirement of 3–5 mg must be
obtained from animal by-products in the diet
 Vitamin B12 is needed for normal erythropoiesis and for
neuronal integrity
 It is a cofactor needed for the isomerization of
methylmalonyl coenzyme A to succinyl coenzyme A, and
for the conversion of homocysteine into methionine (which
also utilizes 5-methyl THF).
 Vitamin B12 is also involved in the control of folate
metabolism, and B12 and folate are required for
intracellular nucleoside synthesis.
 Deficiency of vitamin B12 ‘traps’ folate as methylene
tetrahydrofolate, yielding a macrocytic anaemia with
megaloblastic erythropoiesis in the bone marrow, and
possible neurological dysfunction,

i.e. peripheral neuropathy, subacute combined

degeneration of the spinal cord, dementia and optic
neuritis.
 Vitamin B12 deficiency due to a lack of gastric
intrinsic factor results in pernicious anemia
 This type of megaloblastic anemia causes neurological
damage if it is not treated
 Treatment of Vitamin B12–deficient megaloblastic
anemia with folic acid may improve the symptoms
however, neurological damage may still occur if
vitamin B12 intake is not supplemented.
 Vit. B12 is essential for CNS function and formation of
myelin sheath
 Preparations & dosage :
• Given intramuscularly ( alone ) or in combination with
intrinsic factor orally
 Cyanocobolamine injection ( 100 - 1000 ug / ml)
 Vit. B12 + intrinsic factor capsules and tablets given orally
 Dose :
 1000 ug / day for 2 weeks then 100 - 200 ug monthly for
life time
 Folic acid :

 Is a water soluble member of vit. B12

 Folic acid is essential for the synthesis of nucleoproteins

 present in yeast , liver , fresh green vegetables .

 It is destroyed by prolonged cooling

 Folic acid or folate salts are administered to correct

folate-deficient megaloblastic anemia
 Dose : 10 - 20 mg / day orally
 Rapidly dividing cells are highly sensitive to folic
acid deficiency.

 Antifolate drugs are useful in the treatment of various

infections and cancers.

 In vitamin B12 deficiency, folates accumulate as N 5-
methyltetrahydrofolate; the supply of tetrahydrofolate is
depleted; and the production of red blood cells slows.

 Administration of folic acid to patients with vitamin B12

deficiency helps refill the tetrahydrofolate pool and partially or
fully corrects the anemia.
 The exogenous folic acid does not correct the neurologic
defects of vitamin B12 deficiency.
 vitamin B12 deficiency must be ruled out before one
selects folic acid as the sole therapeutic agent in the
treatment of a patient with megaloblastic anemia
 Supplementation with folate at the time of conception is
known to reduce the risk of neural tube defects in the
offspring
 Erythropoietin
 Erythropoietic agents stimulate erythropoiesis, and therefore
increase the red blood cell production rate
 Available erythropoietic agents include epoetin alfa, and
darbepoetin alfa
 They are glycoproteins manufactured by recombinant DNA
technology that have the same biological activity as endogenous
erythropoietin.
 The amino acid sequence of epoetin alfa is identical to
endogenous protein; however,BYthe
12/12/22
carbohydrate structure differs.34
Debela G
 Epoetin alfa is used for anemia of chronic kidney failure.

 Epoetin alfa may be administered by either the IV or subcutaneous

(SC) routes.

 Bioavailability with SC administration is poor

 Darbepoetin alfa differs from epoetin alfa by the addition of two

N-linked carbohydrate side chains.

 Darbepoetin alfa has a longer half-life and prolonged biological

activity compared with epoetin

12/12/22 alfaG
BY Debela 35
 The prolonged half-life of darbepoetin offers the advantage of less

frequent dosing, starting at once-a-week when given IV

 Evaluation and treatment of iron deficiency should occur prior to

initiation of erythropoietic therapy

 Failure to respond to erythropoietic therapy requires evaluation of

other factors causing resistance, such as infection, inflammation,

chronic blood loss, aluminum toxicity, malnutrition, and

hyperparathyroidism.
12/12/22 BY Debela G 36

 Hypertension is the most common adverse effect

 Dosing and Administration.

 Starting doses of epoetin alfa are 80 to 120 units/kg per week for

SC

 120 to 180 units/ kg per week for IV administration divided in two

to three doses

 If a patient is converted from IV to SC epoetin and is not at the

target Hgb/Hct, the weekly SC dose should remain the same as the
12/12/22 BY Debela G 37

IV dose.
 If they have achieved the target Hgb/Hct, a one-third reduction

in dose is appropriate.

 The starting dose of darbepoetin alfa in patients not previously

receiving erythropoietic therapy is 0.45 mcg/kg IV or SC

administered once weekly.

Aplastic anaemia

 Causes :

 Inhibition of the bone marrow by drugs e.g.

Chloramphenicol & cytotoxic drugs .
 Treatment :

 Removal of the cause , blood transfusion , vit b12 folic

acid , vit. C. , corticosteroids ( 60 mg prednisolone for
3 months ) , testosterone and anabolic steroids .
 Haemolytic anaemia

 Causes : blood haemolysis due to drugs , poison

( snake venom ) ,malignant spleen , incombatible
blood transfusion ... Etc
 Treatment :

• removel of the cause , fresh blood transfusion and

corticosteroids .