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Pharmacology 3
rd
stage D. Tayser
Drugs Used in Treatment of Anemia
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.
Pharmacokinetic of iron:-
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 .
Clinical indications :-
Iron deficiency anaemia is the only indication for iron therapy.
1- Dietary iron deficiency.
2- Chronic blood loss.
3- During pregnancy; where extra demand of iron is required from the 4
th
month of
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.
Adverse effects of oral iron therapy:-
1- Bad taste.
2- Black stool.
3- Irritation of gastric mucosa lead to nausea, vomiting and heartburn.
4- Irritation of intestinal mucosa lead to diarrhea or constipation.
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These side effects are dose related may be overcome by:-
1- 1-decrease the dose
2- taking the tablets with or after the meals .
3- Trying different iron salt .
Parentral iron therapy:-
Parentral iron therapy indicated only when:-
1- 1-Oral iron is not tolerated (vomiting, epigastric pain, constipation or diarrhea … )
2- Failure to absorb oral iron e.g. mal absorption syndrome.
3- Noncompliance.
4- Severe deficiency with chronic bleeding.
There are two types of parentral iron therapy:-
Iron dextran (Inferon)
R
1- high molecular weight
2- Can give 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.
Iron sorbitol –citrica ( Jectofer )
R
:-
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.
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 thrombophlebitis and embolism.
4- Irritation at site of injection, but not like I.M.
5- An anaphylactic 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.
Iron toxicity:-
1- Acute overdose mainly occur in children; Desferrioxamine (dysferal )
R
half-life is 6hs.
; it is 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 .
Side effects:-
Rare, but chronic use may cause cataract, retinal damage, deafness, anaphylactic reaction.
2- Chronic iron overload occur due to-
a. Excessive Parental iron therapy.
b. Repeated blood transfusion as in treatment of Thalassemia.
c. Could be inherited as excessive absorption syndrome of iron called hemochromatosis.
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B12:
Vitamin
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, Colchicine'.
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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, and pyrimidine and lead to decrease DNA and RNA and
lead to megaloblastic anaemia.
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.
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.
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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.
Notes
Mubark A. Wilkins