Anemia is lack of haemoglobin in blood. Iron and other therapies are discussed as a treatment for the condition of Anaemia

1. Anti anaemic Drugs

2. Anti anaemic Drugs
 Haematopoiesis: it is the production of
erythrocytes, platelets, and leukocytes from
undifferentiated stem cells.
 The haemtopoietic machinary reside in the bone
marrow in adults.
 It requires a constant supply of essential nutrients
– iron, cyanocobalamine, folic acid and presence
of hematopoietic growth factors

3. Anti anaemic Drugs
Anemia:
 anemia is a common clinical condition that is
caused by an acquired or hereditary abnormality
of RBCS or its precursor, or it may be a
manifestation of an underlying non hematologic
disorder.
 anemia is defined as a decrease in the circulating
RBC mass; the usual criteria are a Hb of less
than 11.5 G/dl in women and less than 14 G/dl in
men.

4. Anti anaemic Drugs
Signs and Symptoms:
 Patients with a Hb less than 7G/dl will have
symptoms of tissue hypoxia (fatigue, headache,
dyspnea, pallor, angina, tachycardia, visual
impairment, syncopy, lymphadenopathy, hepatic
and or splenic enlargement, bone tenderness,
blood loss in feces, neurologic symptoms.

5. Anti anemic Drugs
Classification of anemia:
1. anemia associated with decrease RBC
production for e.g..
 A) iron deficiency anemia,
 B) megaloblastic anemia
 C) Thalassemia
 D) anemia due to chronic disease and renal
failure.
2. Anemia due to increased RBC destruction:
 Haemolytic anemia
 sickle cell anemia

6. Anti anaemic Drugs
1- Iron:
Total quantity of iron in the body is 4-5G
 65-70% in the form of Hb in RBC
 4% in myoglobin
 1% in various heme compound
 15-30% stored in the form of ferritin and
hemosiderin in RE system, liver, spleen, intestinal
mucosa and bone marrow


7. Anti anaemic Drugs
 Iron is required for Hb production.
 in the absence of adequate iron, small red cells with
insufficient Hb are formed, giving rise to microcytic
hypochromic anemia.
 Iron deficiency occur due to:
(a) inadequate dietary intake as in vegetarians,
malnourished pts.
(b) due to blood loss a in women in heavy menstruation
(c) when iron requirement is increased as in pregnancy
and in growing children.
(d) acute or chronic blood loss
.

8. Anti anaemic Drugs
2, 3- cyanocoblamine and folic acid:
 are required for normal DNA synthesis.
 Deficiency of either of these vitamins
results in impaired production and
abnormal maturation of RBCS giving rise
the characteristic blood and bone marrow
picture known as megaloblastic anemia
4- Erythropoeitin and colony stimulating factors
 are hormones that regulate blood cell
development and proliferation in the bone
marrow.

9. Anti anaemic Drugs
1- Iron preparation:
 Oral iron
 Parenteral iron
A- oral iron
 A) Ferrous sulfate - 325mg - 65mg elemental iron
 B )Ferrous gluconate - 320mg -37mg elemental iron
 C) Ferrous fumarate - 325mg - 106mg elemental iron
B- Parenteral iron: iron dextran 50mg elemental
iron/ml

10. Anti anaemic Drugs
Pharmacokinetics:
 Absorption: iron (Fe++; more readily
absorbed) absorb from duodenum and upper
jejenum → Fe+++ (ferric) in the intestinal
mucosal cell.
 Ferric iron binds with transferrin in plasma and
transported in other tissues and stored as
ferritin and hemosiderin form.
 About 10 -20% of dietary iron is absorbed, for
e.g. a standard diet if contain 10-15mg of iron,
only 1mg is absorbed.
 Absorption ↑when iron requirement is ↑ as in
pregnancy, menstruation, growing children

11. Abs is increased by: glucose, amino acids
& ascorbic acid.
& decreased by : phosphate bicarbonate
bile acids, antacids & tetracycline.
Heme iron in meat Hg & myoglobin can be
absorbed intact.
Iron in vegetables & grains, tightly bound to
organic cpds; < available for abs.

13. Anti anaemic Drugs
Distribution:
 ferric from iron store sites through transferrin
goes in the RBCS.
 200- 400 mg oral elemental iron daily should be
given to correct anemia (27% absorbed ,so 50-
100mg iron can be incorporated in Hb).
 Treatment should be continued for 3-6 months,
this not only to correct the anemia but will
replenish iron stores.
 (Hb should reach normal level in 1-3 months).
 Failure to respond to oral iron therapy may be
due to incorrect diagnosis.

14. Storage:
When free iron levels are H, apoferritin is produced
to sequester iron & protect organs from toxic
effect of excess free iron.
Iron is stored in intestinal mucosal cells & as ferritin,
in macrophages in liver, spleen, & bone.
Elimination:
No mechanism for excretion
Small amounts in feces & bile.

15. Anti anaemic Drugs
Adverse effects:
- Due to oral iron therapy;
 Nausea, epigastric discomfort, abdominal
cramps, constipation, diarrhea, black stool.
 They may be minimized by lowering the daily
dose or by taking iron tablets immediately after or
with meals.

16. Anti anaemic Drugs
 Parenteral iron therapy:
 1. It should be reserved for patients with
documented iron deficiency unable to tolerate or
absorb iron ( patients With post gastrectomy,
previous small bowel resection, malabsorption
syndrome, inflammatory bowel D, noncompliance
of patient, advanced chronic renal Disease .
 2. Patients. With extensive chronic blood loss
who can not be maintained with oral iron alone.

17. Anti anaemic Drugs
 Iron dextran (ferric hydroxide + dextran), 50mg
elemental iron/ml
 Route of administration: I/M, or by I/V infusion in
1-2 hours.
Advantage of IV: eliminates local pain & tissue
staining (SE: IM). + allow delivery of entire iron
dose.
 Also Iron sorbitol (IM
 Most adults needs about 1-2 G (20-40 ml) iron
dextran for iron deficiency anemia.

18. Anti anaemic Drugs
Adverse effects:
 Local pain, tissue staining (brown discoloration of
tissues overlying the inj. site), headache, fever,
arthralgia, nausea, vomiting, bronchospasm, urticaria,
anaphylaxis, and death.
Rare: anaphylactic & death.
Also dextran can cause hypersensitivity rxs.
 Alternative preparations:
Iron-sucrose complex & iron Na+ gluconate complex.
ONLY (IV) less hypersensitivity than dextran.

19. Anti anaemic Drugs
Chronic toxicity:
 known as hemochromatosis, when excess
iron is deposited in heart, liver, pancreas and
other organs cause organ failure and death.
 It occurs in patients with inherited
hemochromatosis (excessive iron absorption),
in patients who receive many red cell
transfusions for long period

20. Anti anaemic Drugs
2- coblamine
 a cobalt containing molecule is along with
folic acid, a cofactor in the transfer of 1-
carbon units, a step necessary for the
synthesis of DNA.
 Impairment of DNA synthesis affects all cells,
but because red blood cells must be produced
continuously, deficiency of either coblamine or
folic acid usually manifests first as anemia
(megaloblastic anemia)
 Deficiency;; anemia, GI symptoms, &
neurologic abnormalities.

21. Anti anaemic Drugs
Pharmacokinetics:
 Source: Meat (liver), eggs, & dairy products.
 coblamine is absorbed from the GIT in the presence of intrinsic
factor, a product of the parietal cells of the stomach.
 Plasma transport is accomplished by binding to transcobalamin II.
 Coblamine is stored in the liver in large amounts; a normal
individual has enough to last 5 years.
It is available in 2 forms
1. cyanocobalamine
2. hydroxy cobalamine has a longer circulating half life.

23. Anti anaemic Drugs
Clinical uses and toxicity:
 Both agents have equivalent effects.
 1. Treatment of naturally pernicious anemia
 2. anemia caused by gastric resection
 Because coblamine deficiency anemia is almost
always caused by inadequate absorption, therapy
should be by replacement of coblamine, using
parenteral therapy.
 No significant toxicity of coblamine occurred

25. 25

26. 26
Uses:
1- Pernicious anemia
2- Neurologic abnormalities
3- Gastrectomy
4- Cyanide poisoning.

27. 27
• Initial therapy: 100-1000 mcg of vit B12 IM
daily or every other day for 1-2 wks
• Maintenance: 100-1000 mcg IM once a month
for life.
• .

28. Anti anaemic Drugs
 administration of folic acid to patients with
coblamine deficiency helps refill the
tetrahydrofolate pool and partially or fully corrects
anemia
 However exogenous folic acid does not correct
the neurologic defects of coblamine deficiency
 [Note: Folic acid administration alone reverses
the hematologic abnormality and, thus, masks the
coblamine deficiency, which can then proceed to
severe neurologic dysfunction and disease.
Therefore, megaloblastic anemia should not be
treated with folic acid alone.

29. Anti anaemic Drugs
Folic acid:
 Like coblamine folic acid is required for normal
DNA synthesis, and its deficiency usually
presents as megaloblastic anemia.
 In addition deficiency of folic acid during
pregnancy increase the risk of neural tube
defects in the fetus

30. Anti anaemic Drugs
Pharmacokinetics:
Source: yeast, liver, kidney, & green vegetables.
 Folic acid is readily absorbed from GIT.
 Only modest amount are stored in the body, so a
decrease in dietary intake is followed by anemia
within few months
Pharmacodynamics:
 Folic acid is converted to tetrahydrofolate by the
action of dihydrofolate reductase

31. Anti anaemic Drugs
 One important set of reactions involving
tetrahydrofolate and dihydrofolate constitutes the
dTMP cycle, which supplies the dTMP required
for DNA synthesis.
 Rapidly dividing cells are highly sensitive to folic
acid deficiency.
 For this reason, antifolate drugs are useful in the
treatment of various infections and cancers

32. Anti anaemic Drugs
Clinical use and toxicity:
 Folic acid deficiency is most often caused by
dietary insufficiency and malabsorption.
 Anemia resulting from folic acid deficiency is
readily treated by oral folic acid.
 Maternal folic acid deficiency is associated with
increased risk of neural tube defects in the fetus,
folic acid supplementation is recommended prior
to and during pregnancy

33. Anti anaemic Drugs
 Folic acid supplements will correct the anemia but
not the neurologic deficits of coblamine
deficiency.
 Folic acid has no recognized toxicity

34. Anti anaemic Drugs
Erythropoietin:
 ERYTHROPOIETN is produced by the kidney
 Reduction in its synthesis is responsible for
anemia of renal failure
 Activation of receptors on erythroid progenitors in
the bone marrow, it stimulates the production of
red cells and increases their release from Bone
Marrow.

35. Anti anaemic Drugs
 Erythropoietin is used for anemia associated with
renal failure and some time effective for patients
with other forms of anemia e.g. primary bone
marrow disorder or anemia secondary to cancer
chemotherapy or HIV treatment, bone marrow
transplantation, AIDS or cancer
 Toxicity: thrombosis ,cardiovascular events when
used along with some other erythropoietic agents

36.  Darbepoetin [dar-be-POE-e-tin] is a long-acting
version of erythropoietin
 Therefore, darbepoetin has decreased clearance
and has a half life about three times that of
erythropoietin.
 Supplementation with iron may be required to
assure an adequate response.
 The protein is usually administered intravenously
in renal dialysis patients, but the subcutaneous
route is preferred.

37.  When erythropoietin is used to target hemoglobin
concentration 11.5g/dl, serious and life-
threatening cardiovascular events, increased risk
of death, shortened time to tumor progression
and/or decreased survival have been observed.
 The recommendations for all patients receiving
erythropoietin include a minimum effective dose
that does not exceed a hemoglobin level of 11.5
g/dl and this should not rise more than 1 g/dL
over a 2-week period.

38.  Agents Used to Treat Sickle-Cell Disease
 Clinical trials have shown that hydroxyurea can relieve
the painful clinical course of sickle-cell disease.
 In sickle-cell disease, the drug apparently increases
fetal hemoglobin levels, thus diluting the abnormal
hemoglobin S (HbS).
 This process takes several months.
 Polymerization of HbS is delayed in the treated patients
so that painful crises are not caused by sickled cells
blocking capillaries and causing tissue anoxia.

39.  Important side effects of hydroxyurea include
bone marrow suppression and cutaneous
vasculitis.
 It is important that hydroxyurea is administered
under the supervision of a physician experienced
in the treatment of sickle-cell disease.

40.  A 22-year-old woman who experienced pain and
swelling in her right leg presented at the emergency
room. An ultrasound study showed thrombosis in the
popliteal vein. The patient, who was in her second
trimester of pregnancy, was treated for 7 days with
intravenous unfractionated heparin. The pain resolved
during the course of therapy, and the patient was
discharged on Day 8. Which one of the following drugs
would be most appropriate out-patient follow-up therapy
for this patient, who lives 100 miles from the nearest
hospital?
 A. Warfarin.
 B. Aspirin.
 C. Alteplase.
 D. Unfractionated heparin.
 E. Low-molecular-weight heparin (LMWH).

41.  A 60-year-old man is diagnosed with deep-vein
thrombosis. The patient was treated with a bolus of
heparin, and a heparin drip was started. One hour
later, he was bleeding profusely from the intravenous
site.The heparin therapy was suspended, but the
bleeding continued. Protamine was administered
intravenously, and the bleeding resolved. The
protamine:
 A. Degraded the heparin.
 B. Inactivates antithrombin.
 C. Activates the coagulation cascade.
 D. Activates tissue-plasminogen activator.
 E. Ionically combines with heparin.