stage
rd
3
Pharmacology
Drugs used in treatment of anaemia
Definition :- blood Hb is below the normal .
Classification :-
1-Microcytic aneamia : - low MCV; due to iron deficiency .
2- Normocytic anaemia :- normal MCV ; either due to blood loss or chronic disease .
3- Macrocytic anaemia :- MCV larger than normal occur due to B12 or folate deficiency .
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:
of iron
Pharmacokinetic
Total body iron 3-5gm (in male more than female ) ; 66%of this iron is in Hb of blood ; iron
cross the intestinal mucosal cell by active transport ;the rate of iron absorption is depend on
storage form of iron ( Ferritin ) and rate of erythropoiesis ;transport from intestinal mucosal
cell to the plasma via transferrin , Iron binds to a protein ( apoferritin ) and form a complex
called (Ferritin)that stored in intestinal mucosal cells and in macrophages ,liver, spleen and
bone . there is no mechanism for excretion of iron ,small amount of iron are lost by
exfoliation of intestinal mucosal cell ,and trace amount excreted in bile ,urine and sweat
( this represented 1 mg /day ) ;Ascorbic acid and other acid increase absorption of iron while
tea ,bran, desferrioxamine and other chelating agents like Tetracycline ,Penicillamine
,Ciprofloxacine ,L.dopa , Carbidopa , are decrease absorption of iron .
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Clinical indications :
Iron deficiency anaemia is the only indication for iron therapy .
1- Dietary iron deficiency .
2- Chronic blood loss .
month of
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During pregnancy ;where extra demand of iron is required from the 4
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gestation .
4- Premature baby ;(iron established at 36 weeks of gestation ).
5- Various abnormalities of GIT as mal absorption syndrome .
6- Early treatment of severe pernicious anaemia with B12 .
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Adverse effects of oral iron therapy :
1-Bad taste .
2- Black stool.
3- Irritation of gastric mucosa lead to nausea, vomiting and heart burn .
4- Irritation of intestinal mucosa lead to diarrhea or constipation .
These side effects are dose related may be overcome by :-
1-decrease the dose
2- taking the tablets with or after the meals .
3- Trying different iron salt .
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al iron therapy :
r
Parent
Parentral iron therapy indicated only when :-
1-Oral iron is not tolerated (vomiting, epigastric pain, constipation or diarrhea … )
2- Failure to absorb oral iron e.g. mal absorption syndrome .
3- Non compliance .
4- Severe deficiency with chronic bleeding .
There are 2 types of parentral iron therapy :-
R
Iron dextran (Inferon)
1-high molecular weight
2- can given I.M., and I.V.
3- if given I.M.10-30 %locally bound (not available to use. ) .
4- its absorption through the lymphatic .
5- not bound to transferrin .
6- not excreted .
7- taken up by macrophages and stored in reticuloendothelial cells .
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:
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citrica ( Jectofer )
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Iron sorbitol
1-low molecular weight .
2- given I.M.
3- not locally bound .
4- directly into circulation .
5- bind to transferrin and may saturate it .
6- 30% excreted in urine .
7- directly available for erythropoiesis .
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Adverse effects of I.V. preparation of iron :
1-Headache ,nausea, vomiting with metallic taste .
2- Allergic reaction as pyrexia, flushing ;sweating and palpitation .
3- May cause thrombophelebitis and embolism .
4- Irritation at site of injection, but not like I.M.
5- An anaphylactoid reaction may lead to vascular collapse and death .
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Adverse effects of I.M. preparation :
1-Pain at site of injection .
2- Very irritant and stain the skin
3- Very rare reports of malignant tumor (skin sarcoma) .
4- Non sorbitol-citrica complex is irritant to kidney tubules .
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Iron toxicity :
is 6hs. ; it is
half life
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Acute overdose mainly occur in children ; Desferrioxamine (dysferal )
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1
iron chelating agent ; its straight chain twins around iron and form a non toxic complex of
great stability ((ferrioxamine )) which is excreted in urine and give red-orange color .
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Side effects :
rare ,but chronic use may cause cataract ,retinal damage ,deafness ,anaphylactic reaction .
2- Chronic iron overload occur due to :-
A-Excessive Parentral iron therapy .
B- Repeated blood transfusion as in treatment of Thalassemia .
C- could be inherited as excessive absorption syndrome of iron called hemochromatosis .
Treatment:
1- Venesection (phlebotomy), in absence of anaemia (450ml/wk.)
2- Desferrioxamine; S.C. infusion
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Vitamin B12
The normal daily requirement of vit.B12 are only 2 microgram ; it would take about 5 years for all of stored
vit.B12 to be exhausted ; there are 2 factors necessary for absorption vitB12 ;Extrinsic factor ( in food) and
intrinsic factor ( glycoprotein ) secreted by parietal cells of stomach ; absorption of vitB12 only when it
combined with intrinsic factor ,this complex absorbed in the distal ileum .
The cobalamin is active cellular coenzyme is necessary for demethylation of tetrahydrofolate (THF ) and thus for
DNA synthesis .
Deficiency extrinsic ,intrinsic factors or their receptors defect lead to B12 deficiency and this lead to :-
1-Megaloblastic anaemia .
2- Degeneration of brain ,spinal cord , and peripheral nerves .
3- Abnormalities of epithelial tissue especially in GIT .
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Indications :
1-Pernicious anaemia (Atrophic gastric mucosa ) .
2- Mal absorption syndrome due to disease or drugs Neomycin ,Colchicines' .
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Folic acid
Folic acid reductase DHFA reductase
Folic acid →→→→→
→→→→Di hydro folic acid(DHFA)→→→→→→→→ Tetra hydro folic acid(THFA)
THFA is important in nucleotide bases synthesis ; deficiency of THFA lead to decrease synthesis of amino acid,
purine , pyrimidine and lead to decrease DNA and RNA and lead to megaloblastic anaemia .
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Indications :
1-Megaloblastic anaemia that occur due to pernicious anaemia ,increase body requirement for folic acid during
pregnancy or due to dietary folic acid deficiency ; Folic acid should not be used alone because vitB12 is
needed for the conversion of folic acid to tetrahydrofolate .
2- Malabsorption syndrome .
3- Prevention of neural tube defect (spina bifida) .
4- With antiepileptic drugs e.g. Phenytoin .
5- Methotrexate toxicity .
6- High doses of Methotrexate with folinic acid in certain malignancies .
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Haemopoietic growth factors
1-Epoetin alpha :-
recombinant derived of human erythropoietin that secreted mainly from kidney lead to increase proliferation
and differentiation of erythrocyte precursors ;it's used for treatment of anaemia of chronic renal failure .
Side effects :- 1) dose dependent hypertension and hypertensive encephalopathy, may occur due to increase
peripheral vascular resistance or due to increase blood viscosity .
2) Iron deficiency anaemia .
2- Colony stimulating factors include :-
A)Recombinant of human granulocyte stimulating factor (G-CSF ) e.g. Filgrastin and Lonograstin
Indications :-
1-Neutrpenia from cytotoxic drugs .
2- Bone marrow transplant to decrease infection .
3- Aplastic anaemia .
4- Acquired immune deficiency syndrome (AIDS) .
Side effects :- dysuria and splenomegaly .
B) Recombinant of human granulocyte –macrophage –colony stimulating factors (G M-CSF ) e.g. molgramostim
Sargramostim .
Indications :-
1-Neutrpenia from cytotoxic drugs .
2- Bone marrow transplant to decrease infection .
3- Aplastic anaemia .
4- Acquired immune deficiency syndrome (AIDS) .
Side effects :- Pleural and pericardial effusion in high dose .