1. Drugs affecting haemostasis, Antianemic drugs A. Kohút

2. Drugs used to treat blood disorders 1. Anticoagulants 1. Anticoagulants 2. Antiagregatory drugs (antiplatelets) 2. Antiagregatory drugs (antiplatelets) 3. Thrombolytics 3. Thrombolytics 4. Antifibrinolitics 4. Antifibrinolitics 5. Drugs for anemia 5. Drugs for anemia

3. Anticoagulants

4. Hemostasis: Injury Platelet Activation Plt-Fusion Blood Vessel Constriction Coagulation Activation Stable Hemostatic Plug Thromibn, Fibrin Reduced Blood flow Tissue Factor Primary hemostatic plug Neural

5. Coagulation: Intrinsic 12,11,9,8 (aPTT-) Extrinsic-7 (PT) Prothrombin  Thrombin Fibrinogen  Fibrin Common Path (TT) FX  FXa

6. Process- primary haemostasis haemostasis In a normal individual, coagulation is initiated within 20 seconds after an injury occurs to the blood vessel damaging the endothelial cells. In a normal individual, coagulation is initiated within 20 seconds after an injury occurs to the blood vessel damaging the endothelial cells. endothelial cells endothelial cells Platelets immediately form a haemostatic plug at the site of injury. This is called primary haemostasis. Platelets immediately form a haemostatic plug at the site of injury. This is called primary haemostasis. Plateletshaemostasis Plateletshaemostasis

9. Secondary haemostasis Secondary haemostasis then follows—plasma components called coagulation factors respond (in a complex cascade) to form fibrin strands which strengthen the platelet plug. Secondary haemostasis then follows—plasma components called coagulation factors respond (in a complex cascade) to form fibrin strands which strengthen the platelet plug.plasmafibrinplasmafibrin Contrary to popular belief, coagulation from a cut on the skin is not initiated by air or drying out, but by platelets adhering to and activated by collagen in the blood vessel endothelium. Contrary to popular belief, coagulation from a cut on the skin is not initiated by air or drying out, but by platelets adhering to and activated by collagen in the blood vessel endothelium.collagenendotheliumcollagenendothelium The activated platelets then release the contents of their granules, these contain a variety of substances that stimulate further platelet activation and enhance the haemostatic process. The activated platelets then release the contents of their granules, these contain a variety of substances that stimulate further platelet activation and enhance the haemostatic process.

12. Mechanism of action of warfarin

13. Comparisson of heparin and warfarin

15. Unfractionated heparin UFH) (UFH) is able to inactivate fa IIa through formation of a tertiary complex, unlike LMWH. UFH binds more to plasma proteins, endothelium and macrophages, resulting in reduced bioavailability and greater patient variability to a given dose. UFH inactivates factors IIa and Xa and affects the aPTT, a measure of anti-factor IIa activity. (aPTT=activated partial thromboplastin time)

16. Low molecular weight size heparin (LMW) LMW heparins are fragments of parent heparins (1/3 of parent compound. Inhibit fa Xa and augment tissue-factor-pathway inhibitor minimally affect thrombin, or factor IIa Thus, a measure of antithrombin (anti-factor IIa) activity (aPTT=activated partial thromboplastin time), is not used to measure the activity of LMW heparins, requires instead a specific anti-Xa assay.

19. Indication and contraindication of anticoagulants Indications Indications  Atrial fibrilation,  Venouse thromboembolism,  Acute myocardial infarction,  Prevention of venous thromboembolism. Contraindications  Severe hypertension,  Recent cerebral haemorhage,  Gastric ulcer,  Severe liver and renal disease,  Pregnancy (warfarin),  Preexisting bleeding disorders.

21. Heparin induced thrombocytopenia

23. Heparin-Antibiotic Interactions The second-generation cephalosporins- cefamandole, cefotetan, and cefoperazone, contain an N-methylthiotetrazole (NMTT) side chain. This NMTT group can: The second-generation cephalosporins- cefamandole, cefotetan, and cefoperazone, contain an N-methylthiotetrazole (NMTT) side chain. This NMTT group can: - Dissociate from the parent antibiotic in solution or in vivo and competitively inhibit vitamin K action, leading to prolongation of the prothrombin time and bleeding. - Dissociate from the parent antibiotic in solution or in vivo and competitively inhibit vitamin K action, leading to prolongation of the prothrombin time and bleeding. - This side chain is also associated with a disulfiram-like reaction to alcohol. - This side chain is also associated with a disulfiram-like reaction to alcohol. - Clinical bleeding has been less frequently reported with Cefotetan than with cefoperazone or cefamandole. - Clinical bleeding has been less frequently reported with Cefotetan than with cefoperazone or cefamandole.

24. Drugs and conditions interacting with warfarin

25. The action of thrombolitics and antifibrinolytics The action of thrombolitics and antifibrinolytics The action of thrombolitics and antifibrinolytics

26. Therapeutic uses of thrombolitics and antitfibrinolytics Thrombolitics : treatment of myocardial infarction, acute thrombotic stroke Thrombolitics : treatment of myocardial infarction, acute thrombotic stroke Antifibrinolytics: excessive bleeding Antifibrinolytics: excessive bleeding after dental extraction in haemophiliacs after dental extraction in haemophiliacs after overdoses of streptokinase after overdoses of streptokinase

27. DRUG USED TO TREAT BLEEDING Vitamin K formation of clotting factors II, VII, IX and X formation of clotting factors II, VII, IX and X given orally, i.m. or i.v. given orally, i.m. or i.v. synthetic preparation (menadiol sodium diphophate) is water soluble and thus not require bile salt for its absorption synthetic preparation (menadiol sodium diphophate) is water soluble and thus not require bile salt for its absorption Clinical use: - bleeding caused by the oral anticoagulants, - hypoprotrombinemia in newborn (intestinal flora is not established) Clinical use: - bleeding caused by the oral anticoagulants, - hypoprotrombinemia in newborn (intestinal flora is not established) Aprotinin - antifibrinolitic Aprotinin - antifibrinolitic Aminocaproic acid, tranexamic acid, - bleeding after fibrinolytic therapy.- inhibit plasminogen activation Protamine sulfate - antagonizes the anticoagulant effect of heparin - positively charged protein interacts with negatively charged heparin to form stable complex without anticoagulant activity

28. Antiagregatory drugs (Antiplatelet drugs)

29. Mechanisms of action of antiplatelet drugs

30. Antianemic drugs

31. Causes of anaemia Inadequate production of red blood cells in bone marrow due to: Inadequate production of red blood cells in bone marrow due to: Lack of raw materials e.g. nutritional anaemia. Lack of raw materials e.g. nutritional anaemia. Depression of bone marrow e.g. chronic infections, drugs, radiation etc. Depression of bone marrow e.g. chronic infections, drugs, radiation etc. Infiltration of bone marrow in conditions like malignancy. Infiltration of bone marrow in conditions like malignancy. Excessive destruction of red blood cells due to: Excessive destruction of red blood cells due to: Abnormality of haemoglobin like thalassemia, Abnormality of haemoglobin like thalassemia, Deficiency of red cell enzymes like Glucose 6 phosphate dehydrogenase deficiency, Deficiency of red cell enzymes like Glucose 6 phosphate dehydrogenase deficiency, Abnormality of red cell membrane like hereditary sperocytosis Abnormality of red cell membrane like hereditary sperocytosis Auto immune haemolytic anaemias Auto immune haemolytic anaemias Blood loss due to any cause Blood loss due to any cause

32. Megaloblastic anaemia Deficiency of vitamin B12 or folate or both. Deficiency of these nutrients may be due to: Deficiency of vitamin B12 or folate or both. Deficiency of these nutrients may be due to: Decreased intake - vitamin B12 deficiency is seen in strict vegetarians. Over cooking in boiling water reduce folate content in food. Decreased intake - vitamin B12 deficiency is seen in strict vegetarians. Over cooking in boiling water reduce folate content in food. Impaired absorption - due to disease of gastrointestinal tract and surgical resection of intestine. Impaired absorption - due to disease of gastrointestinal tract and surgical resection of intestine. Defective utilisation - due to drugs like few types of cancer drugs and epilepsy drug interfere with metabolism of folic acids. Defective utilisation - due to drugs like few types of cancer drugs and epilepsy drug interfere with metabolism of folic acids. Increased demand - pregnancy, recovery from chronic illness etc. Increased demand - pregnancy, recovery from chronic illness etc.

33. Microcytic anaemia Due to reduced intake or absorption of iron: Due to reduced intake or absorption of iron: Iron poor diet Iron poor diet Malabsorption syndromes Malabsorption syndromes Chronic diarrhoea Chronic diarrhoea Gastrointestinal surgery Gastrointestinal surgery Due to increased loss: Due to increased loss: Gastrointestinal bleeding due to any cause Gastrointestinal bleeding due to any cause Hook worm infestation Hook worm infestation Bleeding disorders Bleeding disorders Excessive menstruation Excessive menstruation Due to increased demands: Due to increased demands: Pregnancy Pregnancy Lactation Lactation Prematurity and low birth weight Prematurity and low birth weight Adolescence Adolescence Chronic illness Chronic illness

34. Types and the treatment of anaemias

35. Hematopoietic growth factors SCF - stem cell factor BFU-E -. burst-forming units erythroblasts CFU-E- colony-forming units erythroid GM-CSF, granulocyte- macrophage colony- stimulating factor interleukin-4, and interleukin-9. EPO - erythropoietin is a specific distal acting factor, which stimulates maturation of CFU-E to mature erythrocytes.

36. Factors involved in the development of anaemia and the role of EPO TNF may inhibit the actions of erythropoietin, IL-1 affect utilization EPO IF-beta and IF-gamma suppress erythropoiesis. administration of EPO can actually improve anemia across a wide range of disease states.