Pharmacology of Drugs Affecting Blood
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The document discusses drugs affecting blood and their mechanisms of action. It describes agents that stimulate or inhibit erythropoiesis, such as iron supplements or vitamin B12/folic acid deficiencies respectively. It also covers platelet aggregation inhibitors like aspirin, anticoagulants like heparin, and thrombolytic drugs like streptokinase used to treat thrombosis. Growth factors that stimulate leukopoiesis and chemotherapy drugs that inhibit it are also mentioned.
![2. In2. In HYPERCHROMICHYPERCHROMIC AnemiasAnemias::
Vitamin BVitamin B1212 ((CyanocobalaminCyanocobalamin))
amp. 0.01%, 0.05%-1 mlamp. 0.01%, 0.05%-1 ml
Folic AcidFolic Acid [Vit[Vit Bc, BBc, B99] – Tab. 1 mg] – Tab. 1 mg
IIII.. AGENTS INHIBITINGAGENTS INHIBITING
ERYTHROPOIESISERYTHROPOIESIS::
Sodium Phosphate liquor labelledSodium Phosphate liquor labelled
Phosphor-32Phosphor-32
55](https://image.slidesharecdn.com/15blood-150722075833-lva1-app6892/85/Pharmacology-of-Drugs-Affecting-Blood-5-320.jpg)
![OVERDOSE withOVERDOSE with FeFe2+2+
COMPOUNDSCOMPOUNDS
Manifestation: lethargy, nausea and vomiting
green then tarry stools, weak and rapid pulse,
hypotension, dehydration, acidosis, and coma.
Treatment: support of airway, respiration, and
circulation. Follow gastric lavage, using a 1%
Sodium Bicarbonate solution, to convert iron to
less irritating, poorly absorbed form.
Deferoxamine (powder for injection: 0.5 g)
chelates IRON by binding ferric ions to
the 3 hydroxamic groups of the molecule
[1 g IM]. 7](https://image.slidesharecdn.com/15blood-150722075833-lva1-app6892/85/Pharmacology-of-Drugs-Affecting-Blood-7-320.jpg)
Pharmacology of Drugs Affecting Blood
- 2. Principal Causes ofPrincipal Causes of a Disturbance of Erythropoiesis :a Disturbance of Erythropoiesis : 1. Hb synthesis is impaired - in Fe2+ deficiency - Microcytic Hypochromic Anemia. 2. Cell multiplication is inhibited – DNA synthesis is insufficient - in deficiencies of Vitamin B12 or Folic Acid - Macrocytic Hyperchromic Anemia. 2
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- 4. AGENTS AFFECTING ERYTHROPOESISAGENTS AFFECTING ERYTHROPOESIS I. AGENTS STIMULATING ERYTHROPOIESIS 1. Used in Hypochromic Anemias A. IN IRON-DEFICIENT ANEMIAS: a) Iron Agents: Ferrous sulfate – caps. 0.25 Ferrous Lactate - pulv, PO 1 g Fercoven – amp. 5 ml Ferrum Lek - amp 5 ml b) Cobalt agents: Coamid – amp. 1%-1 ml B. Hematopoietic Growth Factor: Erythropoietin - vial 2000, 4000, 10,000 IU/mL 4
- 5. 2. In2. In HYPERCHROMICHYPERCHROMIC AnemiasAnemias:: Vitamin BVitamin B1212 ((CyanocobalaminCyanocobalamin)) amp. 0.01%, 0.05%-1 mlamp. 0.01%, 0.05%-1 ml Folic AcidFolic Acid [Vit[Vit Bc, BBc, B99] – Tab. 1 mg] – Tab. 1 mg IIII.. AGENTS INHIBITINGAGENTS INHIBITING ERYTHROPOIESISERYTHROPOIESIS:: Sodium Phosphate liquor labelledSodium Phosphate liquor labelled Phosphor-32Phosphor-32 55
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- 7. OVERDOSE withOVERDOSE with FeFe2+2+ COMPOUNDSCOMPOUNDS Manifestation: lethargy, nausea and vomiting green then tarry stools, weak and rapid pulse, hypotension, dehydration, acidosis, and coma. Treatment: support of airway, respiration, and circulation. Follow gastric lavage, using a 1% Sodium Bicarbonate solution, to convert iron to less irritating, poorly absorbed form. Deferoxamine (powder for injection: 0.5 g) chelates IRON by binding ferric ions to the 3 hydroxamic groups of the molecule [1 g IM]. 7
- 8. HEMATOPOIETIC GROWTH FACTORSHEMATOPOIETIC GROWTH FACTORS:: ERYTHROPOETINERYTHROPOETIN Granulocyte Colony-Stimulating Factor -Granulocyte Colony-Stimulating Factor - G-CSF,G-CSF, FILGRASTIMFILGRASTIM Granulocyte-Macrophage Colony-StimulatingGranulocyte-Macrophage Colony-Stimulating Factor - GM-CSF,Factor - GM-CSF, MOLGRAMOSTIMMOLGRAMOSTIM 88
- 9. Folate Deficiency:Folate Deficiency: 1) Increased Demand1) Increased Demand (pregnancy and lactation)(pregnancy and lactation) 2)2) Poor AbsorptionPoor Absorption causedcaused by pathology ofby pathology of the small intestinethe small intestine 3) Alcoholism3) Alcoholism 4) Treatment with Drugs4) Treatment with Drugs that arethat are DihydrofolateDihydrofolate Reductase InhibitorsReductase Inhibitors –– MethotrexateMethotrexate TrimethoprimTrimethoprim BiseptolBiseptol A primary result ofA primary result of folic acidfolic acid deficiency isdeficiency is Megaloblastic AnemiaMegaloblastic Anemia 99
- 10. The minimal requirement: ≈ 1 μg/day. 10
- 11. AGENTS AFFECTING LEUCOPOIESISAGENTS AFFECTING LEUCOPOIESIS 1. Agents Stimulating Leucopoiesis:1. Agents Stimulating Leucopoiesis: Sodium nucleinateSodium nucleinate PentoxylPentoxyl MethyluracilMethyluracil MolgramostimMolgramostim FilgrastimFilgrastim 2. Agents Inhibiting Leucopoiesis:2. Agents Inhibiting Leucopoiesis: CyclophosphamideCyclophosphamide DopanDopan NovembichinNovembichin MyelosanMyelosan MercaptopurineMercaptopurine MethotrexateMethotrexate 1111
- 12. FILGRASTIMFILGRASTIM (G-CSF),(G-CSF), lineage-specific Growth Factorlineage-specific Growth Factor –– supports:supports: Proliferation, Differentiation andProliferation, Differentiation and Functional activity of NeutrophilsFunctional activity of Neutrophils causing a rapid rise incausing a rapid rise in WBCsWBCs withinwithin 2-3 days2-3 days in patients with normal bone marrow function orin patients with normal bone marrow function or 7-14 days7-14 days in patients with bone marrow suppression.in patients with bone marrow suppression. Clinical use:Clinical use: •• to decrease incidence of infectionto decrease incidence of infection afterafter CANCER CHEMOTHERAPYCANCER CHEMOTHERAPY •• Bone Marrow TransplantationBone Marrow Transplantation in cancer patientsin cancer patients •• Chronic severeChronic severe Neutropenia, AgranulocytosisNeutropenia, Agranulocytosis,, •• Pancytopenia, Acute LeukaemiaPancytopenia, Acute Leukaemia •• Myelodysplastic SyndromeMyelodysplastic Syndrome •• Hematologic toxicity with drug therapy.Hematologic toxicity with drug therapy. 1212
- 13. AGENTS USED FOR PROPHYLAXIS ANDAGENTS USED FOR PROPHYLAXIS AND TREATMENT OF THROMBOSISTREATMENT OF THROMBOSIS 1.1. PLATELET AGGREGATION INHIBITORSPLATELET AGGREGATION INHIBITORS 2.2. ANTICOAGULANTSANTICOAGULANTS 3.3. THROMBOLYTIC AGENTSTHROMBOLYTIC AGENTS 1313
- 14. PLATELET AGGREGATION INHIBITORSPLATELET AGGREGATION INHIBITORS (ANTIPLATELET AGENTS):(ANTIPLATELET AGENTS): Aspirin, Ticlopidine, Dipyridamole,Aspirin, Ticlopidine, Dipyridamole, Pentoxifylline, AbciximabPentoxifylline, Abciximab Clinical Uses:Clinical Uses: AMI, Prior MI,AMI, Prior MI, Unstable or Stable Angina,Unstable or Stable Angina, Stroke,Stroke, Transient Ischemic Attack,Transient Ischemic Attack, Arterial Bypass Surgery,Arterial Bypass Surgery, Angioplasty,Angioplasty, Peripheral Vascular DiseasePeripheral Vascular Disease.. 1414
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- 16. ASPIRINASPIRIN blocksblocks Thromboxane AThromboxane A22 synthesissynthesis fromfrom arachidonic acidarachidonic acid in plateletsin platelets byby irreversibleirreversible AcetylationAcetylation andand Inhibition of COXInhibition of COX –– a key enzyme ina key enzyme in PGPG andand TxATxA22 synthesis.synthesis. ASPIRINASPIRIN 75 - 325 mg/day75 - 325 mg/day is the Most Widely Tested Regimen.is the Most Widely Tested Regimen. 1616
- 17. TiclopidineTiclopidine andand ClopidogrelClopidogrel inhibit theinhibit the ADPADP pathwaypathway involved in the binding ofinvolved in the binding of plateletsplatelets toto fibrinogenfibrinogen andand to each other.to each other. Adverse Effects:Adverse Effects: Prolonged BleedingProlonged Bleeding NeutropeniaNeutropenia TheyThey are reservedare reserved for patientsfor patients who cannot toleratewho cannot tolerate ASPIRINASPIRIN.. 1717
- 18. DipyridamoleDipyridamole ((Curantil, PersantineCurantil, Persantine) -) - a coronary vasodilator which was introduceda coronary vasodilator which was introduced forfor Angina PectorisAngina Pectoris.. Mechanism of actionMechanism of action:: it inhibitsit inhibits PDEPDE andand blocks reuptake ofblocks reuptake of AdenosineAdenosine to increaseto increase plateletplatelet cAMPcAMP which inhibitswhich inhibits TxATxA22 synthesis andsynthesis and potentiates the effect ofpotentiates the effect of Prostacyclin (PGIProstacyclin (PGI22)) toto antagonizeantagonize Platelet StickinessPlatelet Stickiness andand Platelet AdhesionPlatelet Adhesion toto ThrombogenicThrombogenic Surface.Surface. 1818
- 19. Pentoxifylline (Pentoxifylline (TrentalTrental)) inhibits PDEinhibits PDE,, Platelet and ErythrocytesPlatelet and Erythrocytes Aggregation,Aggregation, has desaggregational properties,has desaggregational properties, enhances fibrinolysis, lowers viscosity,enhances fibrinolysis, lowers viscosity, IMPROVES MICROCIRCULATIONIMPROVES MICROCIRCULATION.. 1919
- 20. ABCIXIMABABCIXIMAB ReoPro 2 mg/mlReoPro 2 mg/ml IV injectionIV injection a Humanized Monoclonal Antibodya Humanized Monoclonal Antibody directed against the plateletdirected against the platelet GlycoproteinGlycoprotein IIb/IIIa Receptor ComplexIIb/IIIa Receptor Complex andand inhibits platelet aggregation.inhibits platelet aggregation. 2020
- 21. II. ANTICOAGULANTS:II. ANTICOAGULANTS: 1. DIRECT ACTION1. DIRECT ACTION HEPARIN -HEPARIN - amp 5 ml – 5000 U/ml and 10000 U/mlamp 5 ml – 5000 U/ml and 10000 U/ml FRAXAPARIN -FRAXAPARIN - syringe 0.3 ml, 0.5 ml, 1 ml (1 ml-9,500 IU)syringe 0.3 ml, 0.5 ml, 1 ml (1 ml-9,500 IU) ENOXAPARINENOXAPARIN SODIUM HYDROCITRATESODIUM HYDROCITRATE 2. INDIRECT ACTION2. INDIRECT ACTION Neodicumarin - Tab 0.05 and 0.1 gNeodicumarin - Tab 0.05 and 0.1 g Warfarin - Tab 2 and 10 mgWarfarin - Tab 2 and 10 mg Phenylin - Tab 0.03 gPhenylin - Tab 0.03 g Syncumar - Tab 2 and 4 mgSyncumar - Tab 2 and 4 mg 2121
- 22. HeparinHeparin Mechanism of actionMechanism of action:: acts indirectly by binding toacts indirectly by binding to Antithrombin III.Antithrombin III. TheThe Heparin-AT III complexHeparin-AT III complex binds tobinds to clotting factors of intrinsic pathways –clotting factors of intrinsic pathways – IIa,IIa, Xa, IXa, XIa, XIIa and XIIIaXa, IXa, XIa, XIIa and XIIIa andand inactivates theminactivates them.. 2222
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- 24. CONTRAINDICATIONS toCONTRAINDICATIONS to HeparinHeparin:: Bleeding Disorders, ThrombocytopeniaBleeding Disorders, Thrombocytopenia Hypertension, Threatened Abortion, Piles, UlcersHypertension, Threatened Abortion, Piles, Ulcers Subacute Bacterial EndocarditisSubacute Bacterial Endocarditis Large MalignanciesLarge Malignancies, Tuberculosis (Hemoptysis)Tuberculosis (Hemoptysis) Ocular and Neurosurgery, lumbar punctureOcular and Neurosurgery, lumbar puncture 2424
- 25. ADVERSE EFFECTS of HEPARINADVERSE EFFECTS of HEPARIN:: 1. Bleeding complications.1. Bleeding complications. Excessive bleeding may be managed by suspendingExcessive bleeding may be managed by suspending the drug or treating withthe drug or treating with PROTAMINE SULFATEPROTAMINE SULFATE.. 2. Hypersensitivity reactions: chills, fever, urticaria,2. Hypersensitivity reactions: chills, fever, urticaria, Anaphylactic Shock.Anaphylactic Shock. 3. Thrombocytopenia.3. Thrombocytopenia. 2525
- 26. Clinical usesClinical uses ofof HeparinHeparin:: Pulmonary Embolism andPulmonary Embolism and Deep Vein ThrombosisDeep Vein Thrombosis Myocardial Infarction and Unstable AnginaMyocardial Infarction and Unstable Angina Prevention of ThromboembolismPrevention of Thromboembolism Intravascular CathetersIntravascular Catheters Disseminated Intravascular Coagulation Syndrome 2626
- 27. Vitamin KVitamin K is regenerated from theis regenerated from the EPOXIDEEPOXIDE byby vitamin K Epoxide Reductase.vitamin K Epoxide Reductase. It is the enzyme that is inhibited by:It is the enzyme that is inhibited by: NeodicumarinNeodicumarin SyncumarSyncumar WarfarinWarfarin NEODICUMARINNEODICUMARIN (tab. 0.05 and 0.1 g) –(tab. 0.05 and 0.1 g) – a coumarin derivative.a coumarin derivative. Mecahnism of actionMecahnism of action:: It inhibits the hepatic synthesis and activation ofIt inhibits the hepatic synthesis and activation of vitamin K-dependent clotting factors II, VII, IXvitamin K-dependent clotting factors II, VII, IX andand X,X, decreasing the blood’s coagulation potential.decreasing the blood’s coagulation potential. 2727
- 28. Clinical Uses ofClinical Uses of NeodicumarinNeodicumarin:: ThrombophlebitisThrombophlebitis Deep Vein ThrombosisDeep Vein Thrombosis Myocardial InfarctionMyocardial Infarction Artificial Heart ValvesArtificial Heart Valves Atrial ArrhythmiasAtrial Arrhythmias 2828
- 29. FIBRINOLYTIC (THROMBOLYTIC) DRUGSFIBRINOLYTIC (THROMBOLYTIC) DRUGS I. Non-selective Activators of Profibrinolysin:I. Non-selective Activators of Profibrinolysin: StreptokinaseStreptokinase UrokinaseUrokinase StreptodekaseStreptodekase II. Selective activators of Profibrinolysin:II. Selective activators of Profibrinolysin: AlteplaseAlteplase 2929
- 30. StreptokinaseStreptokinase (amp 250,000 and 500,000 IU) -(amp 250,000 and 500,000 IU) - a non-selective Activator ofa non-selective Activator of ProfibrinolysinProfibrinolysin,, the enzyme extracted from cultures ofthe enzyme extracted from cultures of Hemolytic Streptococci.Hemolytic Streptococci. It activatesIt activates Plasminogen (Profibrinolysin)Plasminogen (Profibrinolysin) of thrombus andof thrombus and serum to formserum to form Plasmin (Fibrinolysin),Plasmin (Fibrinolysin), whichwhich degrades fibrindegrades fibrin and break upand break up thrombithrombi.. 3030
- 31. AlteplaseAlteplase andand DuteplaseDuteplase -- recombinantrecombinant tissue-typetissue-type Plasminogen ActivatorPlasminogen Activator ((t PAt PA) -) - act selectively on plasminogen,act selectively on plasminogen, bound with thrombus and arebound with thrombus and are ‘‘CLOT SELECTIVE’CLOT SELECTIVE’ 3131
- 32. Agents to Treat Bleeding (Agents to Treat Bleeding ( HemostaticsHemostatics)) 1.Agents enhancing Coagulation of blood1.Agents enhancing Coagulation of blood:: forfor Local ApplicationLocal Application:: Thrombin - amp 125 AUThrombin - amp 125 AU Sponges hemostaticSponges hemostatic System ActionSystem Action:: GelatinGelatin FibrinogenFibrinogen Calcium chloride, Calcium gluconateCalcium chloride, Calcium gluconate AdroxonAdroxon Dicynon (Etamsylat)Dicynon (Etamsylat) Vitamin KVitamin K Protamine sulfateProtamine sulfate 3232
- 33. AdroxonAdroxon ((amp. 0.025% 1 mlamp. 0.025% 1 ml)) Hemostatic actionHemostatic action It is used to stop capillary and parenchymatousIt is used to stop capillary and parenchymatous bleeding in traumas, during surgery and forbleeding in traumas, during surgery and for prevention of post-operative bleeding andprevention of post-operative bleeding and haematomas.haematomas. AdroxonAdroxon is used:is used: a)a) LocallyLocally – gauze bandage or tampon moistened– gauze bandage or tampon moistened with 0.025% solution;with 0.025% solution; b)b) IM or SCIM or SC 0.025% 1 ml 1–4 times0.025% 1 ml 1–4 times during or after surgery.during or after surgery. 3333
- 34. EthamsylateEthamsylate ((DicynoneDicynone)) – amp. 12.5% 2 ml IV or IM,– amp. 12.5% 2 ml IV or IM, Caps. 0.25 gCaps. 0.25 g Anti-hyaluronidase ActionAnti-hyaluronidase Action –– improvesimproves capillary wallcapillary wall stabilitystability InhibitsInhibits PGIPGI22 productionproduction Corrects abnormal platelet functionCorrects abnormal platelet function Clinical usesClinical uses:: Prevention and Treatment ofPrevention and Treatment of Capillary Bleeding in:Capillary Bleeding in: MenorrhagiaMenorrhagia after Abortion, Postpartum Haemorrhageafter Abortion, Postpartum Haemorrhage Epistaxis (nosebleed)Epistaxis (nosebleed) Malena (tarry stool)Malena (tarry stool) HaematuriaHaematuria after tooth extraction.after tooth extraction. 3434
- 35. 35 2. ANTIFIBRINOLYTIC AGENTS Inactivation of the Fibrinolytic System can be achieved by Plasmin Inhibitors : Aminocaproic acid (5% sol.-100 ml) Tranexamic acid Amben (Pamba - amp. 1% sol.-5 ml) Contrical (Aprotinin, Trasylol) All agents inhibit plasminogen activation.
- 36. Thank You for Attention!