This document provides an overview of drugs acting on blood forming organs. It discusses drugs used to treat different types of anemias, including iron supplements, vitamin B12, folic acid, and erythropoietin. It also covers hematopoietic growth factors that stimulate white blood cell and platelet production. The document reviews anticoagulants and antiplatelet drugs that prevent abnormal blood clotting. These include heparin, warfarin, direct thrombin inhibitors, and fibrinolytics used to treat blood clots. Finally, it discusses drugs for bleeding disorders, such as desmopressin, plasma fractions, and fibrinolytic inhibitors.

1. AN OVERVIEW OF DRUGS
ACTING ON BLOOD FORMING
ORGANS
Department of Clinical Pharmacology and Therapeutics
ABUTH Zaria
By
Dr Bakut JM
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2. OUTLINE
• Introduction
• Overview of Anaemias
• Overview Haematopoitic Agents
• Overview of Coagulation and Anticoagulants
• Overview of Antithrombotics
• Overview of thrombolytics
• Overview of agents use in bleeding disorders
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3. INTRODUCTION
• Blood is a tissue composed of cells (45%) and plasma (55%)
• Blood cells in the vascular space: RBCs, WBCs, Platelets, Megakaryocytes,
Reticulocytes
• Plasma consist: Water (90% of plasma), protein (clotting factor, antibodies), ions,
waste, gases
• Sites of hematopiosis
 Prenatal sites: Yolk sac, liver, Spleen, Bone marrow
Birth – Adulthood: Tibia, Vertebrae, Pelvic bone, Sternum, Ribs, Femur, Lymph
nodes
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4. OVERVIEW OF ANEMIA
• Anemia refers to a blood condition of the deficiency of haemoglobin for age and
gender. Normal range for men (13.5 – 17.5 g/dl), women (12.5 – 15.5 g/dl) and
children have higher levels
• Causes
 Hematopoiesis substrate deficiency; Iron, Vitamin B12, Folate
Bleeding
Suppression of hematopoiesis ; due to liver disease, kidney disease, hypothyroidism,
infections, cancers
Genetic disorders; Sickle cell anaemia, Thalassemia
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5. TYPES OF ANEMIAS
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Type of Anaemia Causes Manifestation
Iron Deficiency
Anaemia
.Inadequate dietary
intake
.Chronic blood
loss(cancer, GIT
infestation, ulcers)
.Malabsorbtion(Coeliac)
.Pregnancy
. Low heamoglobin conc
. Microcytic hypochromic anaemia
Megablastic
Anaemia
. Def of Vit B12
. Poor utilization of Vit
B12
. Def of intrinsic
factors-GIT protein for
uptake of vit B
. Folic acid deficiency
. Malabsortion caused
by drugs like
Phenytion, Neomycin
. Large RBCs
. Fragile RBCs

6. Aplastic anaemia Suppresion of bone
marrow by radiation,
Chemical(Benzene),
Drugs
(Sulphanamides,),
Viral infection (HIV,
Hepatitis, influenza,
parvovirus B19, CMV)
Decrease production
of all cell lines
Can be fatal
Sickle cell anaemia Recessive genetic
disorder in which
valine replaces
glutamic acid at the
th
. Sickle-shaped cells
. other abnormally
shaped cells
.Cells may become11/2/2023
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7. DRUGS USE IN THE MANAGEMENT OF ANEMIA
1. Iron deficiency anemia:
Iron therapy;
Mechanism of action: Required for biosynthesis of heme and heme-
containing protein like hemoglobin, myoglobin
Oral iron therapy: Ferrous sulphate(Desiccated 200 mg, Hydrated 325 mg, with 60
mg elemental iron), Ferrous gluconate (325 mg, 36 mg elemental iron), Ferrous
fumarate(325 mg, 36 mg elemental iron)
Parenteral iron therapy;
• Iron dextran: stable complex of ferric oxyhydroxide and dextran polymers
containing 50 mg/ml elemental iron. Given deep intramuscular in Z-pattern/iv in
infusion
• Sodium ferric gluconate complex and Iron-sucrose complex: given iv only.
• Incase of hemochromatosis (iron toxicity), deferoxamine (Deferasirox) can be used
to chelate iron
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8. 2. MACROCYTIC ANEMIA(TREATMENT WITH VIT B12)
Mechanism of action: cofactor for the production of tetrahydrofolate, converts
homocysteine to methionine and metabolize L-methylmalonyl-CoA
Parenteral Cyanocobalamin or hydroxocobalamin (Vitamin B 12), given IM 1000 mcg daily
for 1 -2 weeks to replenish stores
Oral Vit B 12, 1000 mcg daily
Folic acid: Mechanism of action: Precursor of methyl groups used for synthesis of
amino acid, purines, deoxynucleotide
Oral 1 mg daily can reverse megaloblastic anemia.
5 mg tablet widely available
Supplementation in pregnancy, alcohol dependance, hemolytic aneamia, liver disease, skin
disease, renal dialysis
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9. HEMATOPOIETIC AGENTS
1. Erythropoietin: a glycoprotein produced in the kidneys of anemic patients
Mechanism of action: Agonist of erythropoietin receptors expressed by red
cell progenitors
• Originally purified from human urine of patients with severe anemia.
Recombinant human erythropoietin (Epoitin alfa).
2. Darbepoetin alfa has longer half life. 2000 - 40000 IU subcutaneously.
• Recipients: Chronic renal patients, HIV infected on zidovudine, myelosuppressive
cancers, patients schedule for surgery, those who don’t take transfusion for sake
of believe
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10. MYELIOD GROWTH FACTORS
G-CSF and GM-CSF are growth factors originally from cultured human cell lines.
Mechanism of action: stimulates G-CSF receptors expressed on mature neutrophil
and their progenitors.
• Filgrastim: A recombinant human G-CSF produced in bacterial expression system, non-
glycosylated peptide of 175 amino acids
• Sargramostim: Recombinant human GM-CSF produced in a yeast expression system.
Glycosylated peptide of 127 amino acids. IV or subcutaneous
• Pegfilgrastim: covalent conjugated product of Filgrastim and polyethylene glycol.
Injected once per myelosuppressive chemotherapy cycle.
• Lenograstim: Glycosylated form of recombinant G-CSF.
• Uses: chemotherapy, chronic neutropenia, recovering bone marrow transplant, donor
stem cell transplant, idiopathic thrombocytopenia
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11. MEGAKARYOCYTE GROWTH FACTOR
Mechanism of action: Recombinant form of an endogenous cytokine
activates IL-11 receptors
• Interleukin-11: protein produced by fibroblast and stromal cells.
• Oprelvekin: recombinant for of IL-11. produced by expression of E. coli. Given
subcutaneously.
• Others are Romiplostim, Eltrombopag
• Clinical use: approved for prevention of thrombocytopenia in patients receiving
cytotoxic drugs
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12. ANTICOAGULANTS
• A perfect anticoagulant does not exist.
• An ideal one should prevent pathologic thrombosis, limit reperfusion injury and
allow normal response to vascular injuries with limitation to bleeding
• Note***Revise physiology of coagulation
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13. MECHANISM OF BLOOD COAGULATION
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14. 11/2/2023
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15. A. INDIRECT THROMBIN INHIBITORS
1. Heparin: heterogenous mixture of sulfated mucopolysaccharides (repeating units of
D-glucosamine, D-glucuronic acid and L-iduronic acid) with mean MW of 12000
Daltons
Mechanism of action: Acts by potentiating the action of antithrombin III.
Antithrombin III is believed to be the most potent physiological inhibitor of
coagulation.
Antithrombin inhibits clotting factor proteases especially thrombin (IIa), IXa, and
Xa, by forming equimolar stable complexes with them.
Types
a. Unfractionated Heparin(Has high molecular weight) 5000-30,000.
b. Low molecular weight Heparin; Enoxaparin, Dalteparin, Tinzaparin. Inhibit factor X
and has minimal effect on thrombin.
c. Fondaparinux: synthetic penta-saccharide, binds to antithrombin and enhances its
inactivation of factor X
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16. HEPARIN
MONITORING:
• Activated partial thromboplastin time for patients on heparin
 Blood levels determined by protamine titration level (Normal levels 0.2-0.4
unit/ml)
 Also Anti Xa level (normal 0.3-0.7units/ml)may be use in monitoring LMW
Heparin
TOXICITY
• Bleeding, Reversible alopecia, Allergies, HIT (Heparin induced thrombocytopenia)
REVERSAL
• Protamine sulfate: basic positively charged peptide. It bind to heparin (Negatively
charged) to make stable.
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17. B. ORAL DIRECT FACTOR XA INHIBITOR
• Mechanism of Action: inhibits factor Xa in the final common pathway of
clotting
• Rivaroxaban and Apixaban
• For prevention of DVT following hip replacement surgery and other risk for DVT
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18. C. DIRECT THROMBIN INHIBITORS
1. Parenteral direct thrombin inhibitors
• Hirudin (from Hirudo medicinalis, a leeche), a specific irreversible thrombin inhibitor found
in the saliva of the leeches
• Lepirudin: a recombinant hirudin. Approved for in patients with thrombosis related to HIT
• Bivaluridin: bivalent inhibitor of thrombin, administered IV, inhibits platelet activation,
approved for use following coronary angioplasty
• Argatroban, approved for HIT and following coronary angioplasty
2. Oral direct thrombin inhibitor
• Dabigatran (Dabigatran etexilate mesylate)
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19. WARFARIN AND OTHER COUMARIN ANTICOAGULANT
• First identified (Bishyhydrxycoumarin) in spoiled sweet clover and caused
heamorrhagic disease in cattles
• Used as rodenticide in the 1950s
• In humans, it is used as an antithrombotic administered as the sodium salt
Mechanism of action: Blocks the ϓ-carboxylation of several glutamate residues
in prothrombin and factors VII, IX and X as well as the endogenous
anticoagulant protein C and S
Leads to of biologically inactive coagulation factor molecules
Also inhibits vitamin k epoxide reductase
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20. WARFARIN AND OTHER COUMARIN ANTICOAGULANT
TOXICITY: crosses placenta and may cause fetal birth defects, fetal haemorrhagic
disorder, abnormal bone formation, cutaneous necrosis
MONITORING: Prothrombin time (↑)
REVERSAL: Stop the drug, administer vitamin k (phytonadione), fresh frozen plasma,
Prothrombin complex concentrates (Bebulin, proplex T, Factor VIIa)
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21. FIBRINOLYTIC DRUGS
Mechanism of action: Rapidly lyse thrombi by catalysing the formation of
(enzyme) serine protease plasmin from its precurssor, Plasminogen
1. Streptokinase: a protein synthesized by Streptococci that combines with the
proactivator plasminogen. This catalyzes the conversion of inactive plasminogen to active
plasmin
2. Urokinase: human enzyme from the kidneys which converts plasminogen to active
plasmin
3. Plasminogen streptokinase activator complex; Anistreplase
4. Tissue plasminogen activators: Alteplase, Reteplase, Tenecteplase
• Use in myocardial infarction, Pulmonary embolism, DVT, ascending thrombophlebitis
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22. ANTIPLATELETS AGENTS
• These are agents that prevent platelets aggregation and therefore reduce the
tendency of thrombosis, often referred to as antithrombotic
• Aspirin: a cyclo-oxygenase enzyme inhibitor which irreversibly acetylates the cyclo-
oxygenase enzyme in platelets thereby inhibiting the production of thromboxane A2
until the end of its life span
• Ticlopidine, Clopidogrel and Prasugrel: Irreversibly blocks the ADP receptors on
platelets
• Glycoprotein IIB and IIIA platelet receptor blockers; the IIB/IIIA (Fibronectin,
vitronectin and Willebrand factor receptors complex) when activated leads to final
common pathway. Abciximab, Eptifibatide, Tirofiban
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23. ANTIPLATELETS AGENTS
• Dipyridamole and cilostazol: inhibits adenosine uptake and cGMP
phosphodiesterase activity. A vasodilator
• Anti-plateplatelets are used generally in patients with artificial valve, risks for
endothelial injuries and thrombosis
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24. DRUGS USE IN BLEEDING
DISORDERS
1. Vitamin K: activates prothrombin and factors VII, IX, X by participating in their
post-ribosomal modification. Commonly used in neonatal bleeding disorder,
treatment of warfarin toxicity
2. Plasma fractions: concentrates of factor VIII for treatment of hemophilia
3. Desmopresin acetate: increases the activity of factor VIII, used in mild to moderate
hemophilia A
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25. DRUGS USED IN BLEEDING
DISORDERS
4. Fibrinolytic inhibitors:
• Aminocaprioc acid (EACA): competitively inhibits plasminogen activation. Given (5g)
slowly in infusion over 30 mins to prevent hypotension
• Tranexemic acid : analog of aminocaproic acid. Commonly used for gynaecological
bleeding disorders and PPH, Surgical patients
5. Serine protease inhibitors eg Aprotinin; utilizes free plasmin to inhibit fibrinolysis
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26. CONCLUSION
• The advent of Hematinics and other hematopoietic agents have greatly improved
life by reducing the need for transfusion and its attendant risks in deficiency states,
immunosuppressive states, pregnancy and following chemotherapy
• Also, the critical balance that maintains blood in fluid state and prevents bleeding
needs to continue for healthy living. In pathologic states, this may be maintained
using drugs to prevent morbidity and mortality.
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