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‫بسم هللا الرحمن الرحيم‬
‫‪Name : Ahda Jbara‬‬
‫‪Price :‬‬
‫بسم هللا الرحمن الرحيم‬
The previous lecture we take the oral preparations of iron, we will
continue with the parenteral preparations of iron.
 Intravenous Iron Preparations:
1. Iron dextran (imferon) “IV. And IM.”
Containing 50 mg/ml usually the ampule containing 2 ml 50mg per
each ml, given by total dose infusion, we calculate the dose,
calculate the number of ampules dilute them with intravenous
solution……
“Glucosaline, normal saline” and give it by infusion method.
25 mg of iron by an effect on the bone marrow can raise Hb% conc.
By 1%
“Each 1 gm/dl = 7% Hb” …why?
Because the normal level of Hb is 14 gm/dl is equal to 100% Hb
so 1 gm/dl = 100/14 = 7% Hb
Home Work
An anemic patient has Hb conc. 8 gm/dl calculate the intravenous
dose of iron that should be given to this patient
Our target is 14 gm/dl “ normal level of Hb “ so we want to correct
the 8gm/dl toward 14gm/dl
So we need to raise it by 6 gm/dl .
Answer :
Defective Hb = 14 -8 = 6 gm/dl
(Each 1 gm/dl= 7% Hb )
6 gm/dl = 42% Hb
(Each 25 mg iron raise Hb by 1%)
amount of iron needed =
25 * 42 = 1050 mg
and sure we should continue the course of the treatment for
an extra 3 months.
 Intravenous method of course convenient” fitting in well with
a person's needs” , pleasant “No GIT disturbance “ , and
Complete “all calculated amount of iron will be taken by the
patient, there’s no possibility of the non-compliance in this
route of administration “
 Unfortunately
those
may
produce
anaphylaxis
(severe
hypersensitivity
reaction)
that’s
why
administration
of
intravenous iron should be always at hospital because they are
facilities to treat such these emergency conditions.
 Never ever to give intravenous iron at home, you will be in a
trouble and it may end with the patient death :/ .
 Intramuscular Iron preparations :
1. Iron sorbitol “jectofer “ only IM.,Again the ampule containing
2 ml , 50 mg per each ml
2. Iron dextran “imferon” can also be given IM. As well as IV.
 Here intramuscular injection should be very deep using long
needle, why? To avoid leakage of solution from the injected
site, because leakage some of the solution may stain the
injected site dark brown ( ‫ )ل و ا الاء و‬which may last for 1 or 2
years.
So this can be avoided by using deep intramuscular injection and
by using bulky muscle “gluteal muscle “
 May be painful because iron solution is irritant, it’s irritant
on GIT, so how would be inside the muscle, it might be
painful but the patient can tolerate.
 Other minor symptoms as adverse drug reaction (headache
nausea and metallic taste 2 hours after injection.) “ the dr
didn’t mention them “
 Iron toxicity :
Those are sugar coated sweetened tablets “iron tablets “, for
children those are “M&M”.
Why the dr show us this picture? Because many cases of
iron toxicity happened by this way, colored sugar tablets,
carless mother kept her bottle of iron opened nearby her
children, and the children start to eat them as chocolate
accidental iron toxicity.
 Acute: common in children, usually accidental due to
colored sugar coated tablets
‫ ;)تسوومم عرض و‬the other types of
toxicity are criminal and suicidal.
 Corrosive effects on GIT – hematemesis “vomiting of
blood”, diarrhea and hypovolemia due to blood and fluid
loss and can be accompanied by metabolic acidosis.
 Excessive iron  impaired oxidative phosphorylation and
mitochondrial dysfunction cellular death especially the
vital organs ”kidney ,liver ,brain and heart”
 Treatment of acute iron toxicity:
A- Iron chelation ( the most important step) in the blood and
intestine which means that we give exogenous substance
which will bind to iron in the intestine or in the blood and
making an Unabsorbable complex in the intestine, and if it’s
in the blood it will be filtered through glomeruli and it will
not be reabsorbed back again to the circulation , so chelator
will interfere with iron absorption in the intestine and also
it will interfere with renal tubular reabsorption” ,
so it can reduce absorption from intestine and facilitate renal
elimination”.
 At Home : 1. raw eggs and milk "mixed together and give it to the
patient …
 2. Avoid citreous fruit juice “orange juice, lemon
juice and grapefruit juice “why?
 Because citreous fruit juice have high content of vitamin
C which will enhance iron absorption from the intestine.
 Pharmacological chelator : desferrioxamine (desferal) given
IM
or IV for systemic effect or by gastric tube (tube through the mouth
to the esophagus , passing to the stomach ) “ to administer the
solution of desferrioxamine directly to the stomach to chelate the
intestinal content “
Desferrioxamine + Iron will form ferrioxamine (stable, nontoxic,
nonabsorbable and easily excreted complex) and this is the
definition of chelator.
Unfortunately desferrioxmine produce some adverse reaction
but of course it will be milder than iron toxicity itself”
ADRs of desferrioxamine:
1. Tinnitus ( ‫) طءين‬
2. Transient loss of hearing
3. Impairment of night vision
4. Hypotension
5. Allergy
6. Red color urine
7. Blood dyscrasia (malformation of blood elements like
anemia, leukopenia, thrombocytopenia).
B- Oral phosphate or carbonate can be given to
the patient in addition to the chelator, because
phosphate and carbonate
will form iron
“ferrous” phosphate, iron “ferrous” carbonate
which are not absorbable unlike the sulphate.
C- Symptomatic treatment starting with correction
of Acid base, fluid and electrolyte imbalance .
 Chronic toxicity “chronic Iron over load”
 Also called “hemochromatosis”
 In: 1. Prolonged high dose administration of iron preparation.
2. Untreated hemolytic anemia (hemolysis will release Hb
and one of the metabolite is iron which is accumulative substance
and not eliminated effectively, so subsequently it will accumulate
and lead to hemochromatosis.
3. Repeated blood transfusion (a large amount of blood,
large amount of Hb, it will metabolite and one of the metabolite is
iron).
 The
difference
between
hemolytic
anemia
and
blood
transfusion:
Hemolytic anemia: endogenous blood will be hemolysed.
Repeated
blood
transfusion:
exogenous
blood
will
be
hemolysed.
 TT of chronic toxicity :
It depends if the patients is anemic or non-anemic
1. In Non-Anemic  venesection or
blood donation
repeatedly
2. In Anemic
 chelation by 1- Deferiprone(orally)
2Desferrioxamine (IM or IV) ( they can't donate blood )
 Deferiprone for certain period of time to repeatedly
chelate the endogenous iron overload.
 Desferrioxamine : used also in acute toxicity ..
Venesection: Taking blood from the venous
system.
Now let us move to the other part of the lecture  …….
The 2nd important hemtinics:
Vitamin b12
The chemical name (hydroxy and cyanocobalamine)
• Obtained from dietary animal proteins (its not available in plant
origin dietary substances) and
• Produced by intestinal bacteria.
• Needs an intrinsic factor for absorption.(produced by parietal cells
of gastric mucosa ) So in gastric atrophy there is a deficiency in the
intrinsic factors, that will limit the absorption of Vitamin B12;
subsequently, that will lead to megaloplastic anemia called
pernicious anemia .
• Transported by transcobalamin II and stored in the liver.
• Excess is excreted in the urine because it’s water soluble vitamin
(No toxicity with B12 , unlike the iron ).
• Daily need: 0.6 – 1.2 µg and total body content: 3 – 5 mg.
Functions of vitamin B12:
• Is essential in :
succinyl CoA 
function in central
A- Conversion of methylmalonyl CoA to
Important in lipid metabolism and neuronal
nervous system.
Deficiency 
a neurological
degeneration of the cord.”
disease
“Subacute
B- Conversion of homocystiene to methionine
This conversion is linked to folic acid metabolism and
DNA synthesis  Essential for normal production of RBCs.
Deficiency  Megaloplastic macrocytic anemia. (Large RBCs)
combined
That’s why deficiency in both vitamin B12 and folic acid lead to
Megaloplastic anemia.
and there’s
an
important
point
in
megaloplastic anemia that either folic acid or vitamin B12
deficiency ,are hematologically indistinguishable by examination of
blood smear
the same hematological picture “ the
presence
of macrocytes in the (peripheral) blood smear” so our perfect
diagnosis depend on measurement of these 2 vitamins in blood “
patients anemic and the anemia was found to be macrocytic or
megaloplastic so it’s either B12 or Folic acid deficiency ,,how can
we prove the exact deficiency ? By measurement of these two
vitamins, measure conc. Of folic acid and B12 in blood and we can
know the exact deficiency after reading the results.
The following diagram shows you the link between Vitamin B12
and folic acid:
The Dr. mentioned that there is a spelling mistake “it’s not methyle,
it’s methyl “
Methyl FH4 “tetrahydrofolate” will donate one carbon atom in
methyl group to B12 - methylation of B12 to methyl B12 -, then
methyl B12 will assess the conversion of homocysteine into
methionine which is necessary in DNA synthesis and production of
new RBCs. “both are amino acids”.
Causes of vitamin B12 deficiency:
Most common cause: pernicious anemia due to
Intrinsic factor which is due to gastric mucosal atrophy
deficiency
of
Less common
vegetarian”)
cause:
dietary
(less
meat
and
vegans
“strict
Uses of B12:
A- TT of B12 deficiency anemia (parenterally), we can give B12
orally but because the most common cause is pernicious anemia
where the intrinsic factor is deficient so we have to give it
parentally by either IM or IV injection.
B-(rare use) high doses intravenously of hydroxycobalmine in TT of
“cyanide poisoning”, to convert cyanide to cyanocobalamine
which is nontoxic this is the idea of using hyroxycobalamine in
cyanide poisoning.
 In case of anemia we can use either cyano or
hydroxycobalamine but in case of cyanide poisoning only
hydroxycobalamine can be used.
 Failure to respond means wrong diagnosis (because there’s no
noncompliance and there's no undesirable adverse drug effect
that prevent the patient from taking B12)
 Initial TT of pernicious anemia is not only by B12 but also
FA, Fe and K+
(1. FA and Fe because there might be stimulation of
hematopoiesis which need extra amount of iron and folic
acid 2. K+ because B12 enhance the entry of K+ into cells
if K+ not given this will lead to hypokalemia )
So the ideal TT of pernicious anemia is B12, FA, Fe, and K+
 ADRs: None ( B12 is water soluble vitamin excreted by the
kidney )
Again
as
we
said
Megaloplastic anemia due to B12 or
FA deficiency is hematologically indistinguishable.
Where’s the problem? A patient is diagnosed to have
megaloplastic anemia it’s either B12 or folic acid deficiency, if
we give B12 and the pts. Have B12 deficiency there is no
problem…., and if we give the pts. Folic acid alone and he
have FA deficiency also there’s no problem but if we give the
pts. FA alone and he’s B12 deficient, hematological picture
might be corrected ”megaloplast will be normocyte” but the
neurological picture of B12 deficiency might be exaggerated
“subacute combined degeneration of spinal cord”.
As a conclusion before giving B12 or folic acid to a patient
with megaloplastic anemia, we must be 100% sure about the
nature of the deficient factor by measuring the serum
concentration of both the FA and B12.
 Folic acid
Folic acid is called pteroylglutamic acid, it’s called folic acid from
folium-in Latin means leaf-( ‫ )حووو ال ال ك يوو‬, due to high availability
of this vitamin in green leaves (like spinach
it’s full with folic
acid). Also found in liver and yeast
 Daily adult need: 200 µg, which increased in pregnancy.
Note: You should remember that every pregnant woman should
receive prophylactic iron and Folic acid “F&F” to prevent
microcytic and megaloplastic anemia
 Actions:
FA to be activated it has to be in the reduced
form”tetrahydrofolate”.
Dihydrofolate”dietary
form
of
FA”
should be reduced to tetrahydrofolate”FH4” by dihydrofolate
reductase.( look at the picture below)
FH4 –tetrahydrofolate- contains four carbon atoms and four
hydrogen atoms. It acts as a carrier and a donor of methyl
group (one carbon transfer) in many metabolic pathways
especially the link between FA & B12. . As what we already
discussed, it can donate the methyl group to B12 (to methylate
B12) and then this methyl group will be used in converting of
homocysteine into methionine –which is essential in DNA
synthesis.
Another pathway:
Here
Tetrehydrofolate will be oxidized
after
donation
of
methyl
group
to
convert
DUMP
(deoxyuridine
monophosphate)
to
DTMP
(deoxythymidine
monophosphate). This reaction is essential in synthesis of new
DNA which is essential in synthesis of new RBCs.it is a rate
limiting step in DNA synthesis.
Clinical uses for folic acid
Uses of folic acid are either to prevent (prophylactic)
megaloplastic anemia.
A-Treatment of megaloplastic anemia due
deficiency
Caused by:
1. Poor diet “alcoholics” (bad diet quality which
folic acid due to spending money on alcohol)
2. Malabsorption (GIT disease which prevent the
of folic acid)
or to cure
to
folate
is poor in
absorption
3. Chronic use of anti convulsant Drugs.
(Most of the anticonvulsant drugs are microsomal enzyme
inducer such as phenytoin, Carbamazepine, Ethosuximide,
and phenobarbital) all of those are microsomal enzyme
inducer, microsomal enzyme induction need extra amount of
folic acid so chronic use of these drugs ultimately produce
folic acid deficiency.
B-Treatment or prevention of methotrexate toxicity.
By folinic acid (tetrahydrofolate, the reduced form) not folic
acid
In A process called “folinic acid rescue” the dr will talk about
it when we discuss the antineoplastic drugs but briefly
”. If you remember the mechanism of action of methotrexate, it's an
antifolate that its main effect is to prevent the reduction of folic acid
to be in the active form (tetrahyrofolate), depleting the surface of
folic acid, and this is the main mechanism of cytotoxic effects of
methotrexate,
in case of overdose of methotrexate We can save
the rapidly dividing cells, such as the bone marrow cells from this
damaging effect of antifolateWe can give the already reduced form
of folic acid which is called folinic acid (is a tetrahydrofolate, a
reduced form of folate). There is no need for the effect of
dihydrofolate reductase to activate folate. And this is what is called
“Folinic acid rescue”.
C-Prophylactically
for
individuals
at
hazards
from
developing folate deficiency as:
1.
Pregnant women
(Folic acid is essential together with iron starting from early
pregnancy until delivery, to prevent both iron deficiency
anemia and folic acid deficiency).
2.
Premature infants
3.
Chronic hemolytic anemia; needs supplementation of
folic acid but NOT iron because there will be always iron
overload in hemolytic anemia
4.
Prevention of a condition called Spina Bifida (neuronal
tube defect ).in embryology during intrauterine life the
vertebral column will be open initially then with progress of
pregnancy , this neuronal tube will be closed , non-closure of
the neuronal tube called spina bifida . Previous clinical studies
have shown that treatment or prophylactic treatment of
pregnant women with folic acid will reduce the incidence of
development of Spinal Bifida in their new born babies.
 In a previous studies, 2 groups of pregnant women one treated
by folic acid and the other is not, in the treated group the
incidence of spina bifida was very low while the untreated
group show some cases of spina bifida.
 The side effects: None (like B12); SIMPLY because these 2
vitamins are water soluble and extra amount will be easily
eliminated by the kidney.
This diagram shows you the production of the other side of
blood elements, anemia on the RBCs, malformation of the
other blood elements such as WBCs and platelets is shown
here…
pluripotent stem cells of the bone marrow “ ‫خاليووو اتعووو‬
‫ "االغوورا‬,it could be converted to any type or any line of the
WBCs.
stem cells under the effect of certain hematopoietic factor
“HGFs” such as “GM-CSF” granulocytes macrophage colony
stimulating factor( CSF means colony stimulating factor not
cerebrospinal fluid ) .will be differentiated to different
committed progenitor
cells, progenitor means " ‫"السووووو‬
precursor,ancestor,predecessor or father , pluripotent “ ‫اتعوووو‬
‫ ”االغووورا‬multifunctional , committed " ‫ "ال عووو‬so this cells is
promising to differentiate to different mature blood
cells
(erythrocytes ,monocytes ,neutrophils,,,,)
This pic is just to know the hematopoietic growth factors
mainly G-CSF “granulocytes colony stimulating factor”
and
GM-CSF
“granulocytes
macrophage
colony
stimulating
factor”.
 Note : the text boxes contain extra information
:‫فال الشافعي رحمه هللا‬
,‫ وضيق العيش‬,‫ ولكن من طلبه بذل النفس‬,‫ال يطلب أحد هذا العلم بالملك وعز النفس فيفلح‬
.‫وخدمة العلماء أفلح‬
Sorry for any mistakes 
Done by: Ahda Jbara