Course of blood pharmacology

1. Haemopoietic System and
Treatment of Anaemia
By: Dr. ELHAM KHALED MOHAMMED

2. Learning Objective:
 Haemopoietic System
 Anemia and type of anemia
 Treatment of anemia
 The hemolytic anaemia
 Hydroxyuera

3. THE HAEMOPOIETIC SYSTEM

4. The Blood consists of:
red and white blood cells and platelets
Plasma

5. • The most important
site of formation of red
blood cells in adults
The
bone
marrow
• acts as their graveyard
The
spleen

7. Anaemia

8. • Anemia ( meaning lack of blood) is a decrease
in number of red blood cells (RBCs) or less
than the normal quantity of hemoglobin in the
blood.
• However, it can include decreased oxygen-
binding ability of each hemoglobin molecule
due to deformity of hemoglobin .

10. Any process that can disrupt the normal life span
of a red blood cell may cause anemia.
Normal life span of a red blood cell is typically
around 120 days.
Anemia is caused essentially through two basic
pathways. Anemia is either caused by:
a decrease in production of red blood cell or
hemoglobin.
a loss or destruction of blood.

12. 1-Haematinic Agents
-Iron
-B12
-Folic acid

13. IRON:

16. Administration of Iron

17. parenteral Rout of
iron given in this
conditions :

19. Clinical uses of iron salts:

20. Unwanted effects:

21. Iron overload:

23. 1- desferrioxamine
2- Deferiprone
3- Defasirox

26. 2- Folic Acid and Vitamin B12:

31. Mechanism of action: for FOLIC ACID

32. Pharmacokinetic aspects

33. Unwanted effects
Unwanted effects do not occur even with
large doses of folic

34. Clinical uses of folic acid

35. Folic acid:
 Treatment of megaloblastic anaemia
resulting from folate deficiency, which can be
caused by:
poor diet (common in alcoholic individuals)
malabsorption syndromes
drugs (e.g. phenytoin).
 Treatment or prevention of toxicity from
methotrexate, a folate antagonist

36. Prophylactically in individuals at hazard from
developing folate deficiency, for example:
pregnant women and before conception
(especially if there is a risk of birth defects)
 premature infants
patients with severe chronic haemolytic
anaemias

37. VITAMIN B12
Vitamin B12 is a complex cobalamin.
The vitamin B12 preparation used
therapeutically is hydroxocobalamin.
The principal dietary sources are meat
(particularly liver, where it is stored), eggs and
dairy products

38.  The daily requirement is 2–3 μg.
 Absorption requires intrinsic factor (a
glycoprotein secreted by gastric parietal cells).
Vitamin B12, complexed with intrinsic factor,
is absorbed by active transport in the terminal
ileum.

39. It is stored in the liver, the total amount in the
body being about 4 mg.
This store is so large compared with the daily
requirement
that if vitamin B12 absorption stops
suddenly—as after a total gastrectomy— it
takes 2–4 years for evidence of deficiency to
become manifest.

40. Mechanism of action:
Vitamin B12 is required for two main
biochemical reactions in humans.
1. The conversion of methyl-FH4 to FH4 It is
through these mechanisms that the metabolic
activities of vitamin B12 and folic acid are
linked and implicated in the synthesis of DNA

42.  Vitamin B12 deficiency thus traps folate in
the inactive methyl-FH4 form, thereby
depleting the folate polyglutamate coenzymes
needed for DNA synthesis
2. Isomerisation of methylmalonyl-CoA to
succinyl-CoA.
• Through this pathway, cholesterol, fatty acids,
some amino acids and thymine can be used
for gluconeogenesis or for energy production
via the tricarboxylic acid cycle.

43. Coenzyme B12 is an essential co-factor, so
methylmalonyl-CoA accumulates in vitamin
B12 deficiency.
This distorts the pattern of fatty acid synthesis
in neural tissue and may be the basis of
neuropathy in vitamin B12 deficiency

44. Clinical uses of vitamin B12:
Treatment of pernicious anaemia and other
causes of vitamin B12 deficiency, given by
injection
Prophylactically after surgical operations that
remove the site of production of intrinsic
factor (the stomach) or of vitamin B12
absorption (the terminal ileum).

45. Haemopoietic Growth Factors:
Every 60 seconds, a human being must generate
about 120 million granulocytes and 150 million
erythrocytes.
Maintenance of haemopoiesis necessitates a
balance between self-renewal of the stem cells
on the one hand, and differentiation into the
various types of blood cell on the other.
The factors involved in controlling this balance
are the haemopoietic growth factors

46. The haemopoietic growth factor:
Erythropoietin:
• Regulates the red cell line.
• The signal for its production is blood loss and/ or
low tissue oxygen tension
Colony-stimulating factors:
• Regulate the production of leukocytes and platelets
• The main stimulus for their production is infection

47. ERYTHROPOIETIN:
• Erythropoietin is produced in juxtatubular
cells in the kidney.
• Recombinant human erythropoietins are used
to treat symptomatic anaemia caused by
erythropoietin deficiency

48. Darbepoetin, a hyperglycosylated form of
epoetin, have a longer half-life and can be
administered less frequently
Epoetin and darbepoietin are given:
 intravenously
 subcutaneously

49. Unwanted effects:
Transient influenza-like symptoms are common.
Hypertension
Headache
disorientation and sometimes convulsions.
Iron deficiency can be induced because more iron
is required for the enhanced erythropoiesis.
increasing the risk of thrombosis, especially
during dialysis.

50. Clinical Use:
Iron or folate deficiency must be corrected
before starting treatment.
Anaemia of chronic renal failure.
 Anaemia during chemotherapy for cancer.
 Prevention of the anaemia that occurs in
premature infants
Anaemia of AIDS (exacerbated by zidovudine).

51. Colony-stimulating Factors:
Is available as:
 filgrastim
 pegfilgrastim
Lenograstim
it is given parenterally.

52. Clinical Uses of The CSF:
• Colony-stimulating factors are used in
specialist centres:
 To reduce the severity/duration of
neutropenia induced by cytotoxic drugs.
intensive chemotherapy
 For persistent neutropenia in advanced HIV
infection.

53. Haemolytic Anaemia:
• Anaemia associated with increased red cell
destruction can arise from:
1- genetic causes
• e.g. sickle cell disease, Thalassaemia
2- non-genetic causes
• such as autoimmunity , infections and
adverse drug reactions

54. Treatment of Heamolytic Anemia:
• In most forms of haemolytic anaemia, treatment is:
 Symptomatic:
 e.g. analgesia for painful crises in patients with sickle
cell disease
Supportive:
 e.g. attention to fluid balance.
 Oxygen therapy.
 Blood transfusion when essential.
 Treatment of iron overload.
 Provision of adequate folate to support increased red
cell turnover

55. Hydroxycarbamide:
• Hydroxycarbamide (previously known as
hydroxyurea)
• Is a cytotoxic drug that has been used to
lower the red cell and platelet counts in
patients with polycythaemia.
• There were no serious adverse effects, but
long-term safety is uncertain

56. Mechanism of action:
Hydroxycarbamide inhibits DNA
synthesis by inhibiting ribonucleotide
reductase

57. Hydroxycarbamide metabolism gives rise to
nitric oxide, which may contribute to its
beneficial effect in sickle cell disease.
 Some of its beneficial effect in reducing
painful crises could relate to anti-
inflammatory effects secondary to its
cytotoxic action.

58. Administration and unwanted effects
 is administered by mouth once daily in rather
lower starting dose than is used for treating
malignant disease
Reduced doses are used in patients with impaired
renal function.
Myelosuppression, nausea and rashes are the
commonest adverse effects
Animal studies demonstrated teratogenicity

59. Reference:
• RANG AND DALE’S Pharmacology