IC

EM
NA
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T S
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ANDI ALFIA M T
D E PA RT M E N T O F P H A R M A C O L O G Y
FA C U LT Y O F M E D I C I N E
U N I V E R S I TA S TA D U L A K O
DEFINITION OF ANEMIA

Anemia is a decrease in the number of circulating red

blood cells (RBC's) or hemoglobin (Hb)

usual criteria: Hb <12G/dl (W) and <14G/dl in men

↓ oxygen- Clinical
Hypoxi
Anemia binding consequen
a
ability ces
 WHO's Hb thresholds used to define anemia
(1 g/dL = 0.6206 mmol/L)
Hb threshold Hb threshold
Age or gender group
(g/dl) (mmol/l)
Children (0.5–5.0 yrs) 11.0 6.8
Children (5–12 yrs) 11.5 7.1
Teens (12–15 yrs) 12.0 7.4
Women, non-pregnant
12.0 7.4
(>15yrs)
Women, pregnant 11.0 6.8
Men (>15yrs) 13.0 8.1
CAUSES OF ANEMIA
iron deficiency anemia

↓ production of
RBC/Hb
megalobl anemia

Anemia
acute bleeding
Loss/destruction
of blood
haemolytic anaemia
MEAN CELL VOLUME (MCV)
Low MCV <80fl – microcytic
• eg iron deficiency

Normal MCV 80-100 fl – normocytic

• eg acute bleeding; chronic disease

High MCV >100 fl – macrocytic

• eg B12/Folate deficiency
DRUGS FOR ANEMIA
Drugs for iron deficiency and other hypochromic
anemias:
• Iron
• Pyridoxine , Riboflavin , Copper

Drugs for megaloblastic anemia:

• Vitamin B12
• Folic Acid

Hematopoietic growth factors:

• Erythropoietin
• Myeloid GF
• Megakaryosite GF
 IRON DEFICIENCY

malabsorption blood loss

inadequate dietary increasing iron

intake Iron requirement
deficiency
IRON
Oral Iron
• Ferrous sulfate , ferrous gluconate, ferrous fumarate, fe
pyrophospate 1-3 x/day
• Cheapest form of Iron and one of the most widely used

Parenteral
• Iron dextran, ferri sucrose – IM or IV
• Indicated for patients who cannot tolerate or absorb oral iron or
where oral iron is insufficient to treat the condition ie.
Malabsorption syndrome, prolonged salicylate therapy, dialysis
patients
PHARMACOKINETICS
Absorption
• Iron( Fe++) absorb from duodenum and upper jejenum →Fe+++ (ferric) in the
intestinal mucosal cell
Distribution
• Ferric iron binds with transferrin in plasma and transported in other tissues 
B. marrow, iron released  transferrin and transferrin receptor recycled
Storage
• Apoferritin + ferric hydroxide → Ferritin, the storage form of iron
• Ferritin and hemosiderin form in mucosal cells, liver, spleen, and bone marrow

Excretion:
• No mechanism for excretion of iron
• Small amounts lost by exfoliation of intestinal cells into stool
• Trace amounts excreted in bile , urine , & sweat.
FACTORS AFFECTING
ABSORPTION
ADVERSE EFFECTS OF IRON THERAPY

Oral
• Nausea, upper abdominal pain, constipation or diarrhea.

Parenteral
• Local pain & tissue staining – (brown discoloration of tissue
overlying the injection site).
• Headache, light-headedness, fever , arthralgias,
• Nausea , vomiting, back pain, flushing, urticaria,
bronchospasm , & Rarely anaphylaxis & death
 ACUTE ORAL TOXICITY OF IRON
• Necrotizing gastroenteritis with vomiting, abdominal pain, bloody
diarrhea  shock , lethargy & dyspnea
• Severe metabolic acidosis
• Coma  death
Treatment:
• Whole bowel irrigation
• Desferrioxamine (Deferoxamine)
• Orally → for Unabsorbed iron
• Parenteral (IM, IV) → for iron absorbed
• Desferrioxamine + ferric iron → Ferrioxamine → excreted in
urine and bile.
CHRONIC IRON TOXICITY (IRON OVERLOAD)
• Hemosiderosis : a focal or general increase in tissue
iron stores without associated tissue damage
• Hemochromatosis : associated with tissue damage
Treatment:
• Intermittent venesection (phlebotomy) when there is
no anemia
• Chelation (desferrioxamine) for transfusional
overload
FEATURES OF VITAMIN B12 DEFICIENCY
Impairment of DNA synthesis affects all cells but most
apparently RBCs :
• Megaloblastic Anemia
• GI symptoms
• Neurologic abnormalities
• Degeneration of brain and spinal cord (subacute
combined degeneration ) and peripheral nerves.
• Symptoms may be psychiatric & physical:
• Paresthesia & weakness in peripheral nerves spasticity,
ataxia, & other CNS dysfunction
Vitamin B12
• Porphyrin-like ring with a central cobalt atom & nucleotide.
• Cobalamins = various organic groups covalently bound to
cobalt atom
• For theapeutiv dose:
Cyanocobalmin & Hydroxycobalamin
• Hydroxycobalamin --- is preferred because it is highly
protein-bound & therefore remains longer in the
circulation.
• Cyanocobalamin , hydroxycobalamin & other cobalamins
(found in food sources) are converted to active forms
deoxyadenosylcobalamin & methylcobalamin
PHARMACOKINETICS
Route administration
• Mostly parenteral (IM), oral and aerosol

Absorption
• Intrinsic factor (IF) --- a glycoprotein , secreted by parietal cells of gastric
mucosa
• IF-Vit.B12 Complex --- absorbed by active transport in the distal ileum

Distribution
• Transported in plasma bound to the glycoprotein transcobalamin II & is
taken up by tissues where required & stored in hepatocytes

Elimination:
• Not significantly metabolized
• Pass into bile
• Excreted via kidney
USES OF VIT B12

• Pernicious (addisonian) anemia

• After partial or total gastrectomy
• Malabsorption syndromes
• Insufficient dietary intake
• Hydroxycobalamin (Not cyanocobalamin)
• Tobacco amblyopia
• Cyanide toxicity
ADVERSE EFFECTS

• Allergic hypersensitivity reactions

• Antibodies to hydroxycobalamin-transcobalamin
II complex
• Arrhythmias secondary to hypokalemia
FOLIC ACID (PTEROYLGLUTAMIC ACID/VIT B9)
Is inactive
Active form is → tetrahydrofolic acid
Functions
• Is required for synthesis of Amino
acids , purines, pyrimidines, &
DNA ; & therefore in the cell
division Mitotically active tissues
such as erythroid tissues are
markedly affected.
• Anemia
• Congenital malformations
→neural tube defects ( e.g., spina
bifida)
• Vascular disease
FOLIC ACID
Pharmacokinetics
• Route of administration usually oral
• In diet → polyglutamate form
• For absorption → must be converted to → mono-glutamyl form
• Absorbed mostly → in proximal jejunum

Prevention & treatment of folic acid deficiency

• Dietary insufficiency (e.g. in elderly)
• Pregnancy & lactation
• To prevent → congenital malformations →neural tube defects
• High red cell turn over → e.g. in hemolytic anemias
• Premature infants
• Malabsorption syndromes
ADVERSE EFFECTS
• Generally well tolerated
• Rarely :
• G.I. Disturbances
• Hypersensitivity reactions
• Status epilepticus may be precipitated
• Folic acid can partially reverse some of the hematologic
abnormalities of Vitamin B12 deficiency, although the neurologic
manifestations will progress
BLOOD TRANSFUSION

In patients who are severely anemic at presentation, the decision to

transfuse can be a difficult one, particularly in elderly patients at risk for
congestive heart failure due to volume overload

If the anemia is extreme and the patient is critically ill, one unit can be
given initially at a slow rate, in combination with a diuretic, if fluid status
is a concern

In extreme circumstances, isovolemic exchange can be performed

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