Drugs Affecting Hematology System PDF

UNIT IV: Drugs Affecting Hematology System  Objectives By the end of presentation students will be able to: Describe uses and effects of drugs affecting haematology system Describe the classification of drugs used in hematology disorders Discuss th...

UNIT IV: Drugs Affecting Hematology System  Objectives By the end of presentation students will be able to: Describe uses and effects of drugs affecting haematology system Describe the classification of drugs used in hematology disorders Discuss the action of haematology drugs on the body Identify the expected and adverse reactions of drugs affecting haematology system Discuss the nursing responsibility related to drugs affecting haematology system Calculate the drugs dosage accurately.  Hematologic drugs There are numerous agents utilized to maintain, preserve and restore circulation. The three important dysfunction of blood are thrombosis, bleeding and anemia are commonly treated with various agents. The common ones that nurses must REVIEW are the: – Anticoagulants – Antiplatelet – Thrombolytic – Anti-hyperlipidemics – Anti-anemics – Drugs to treat bleeding  Blood Components Erythrocytes/RBCs Leukocytes/WBCs Thrombocytes/platelets Plasma  Platelets Platelets, also called thrombocytes. Their function is to stop bleeding by forming a clot. The normal platelet count is 1,50,000-4,50,000 per microliter of blood.  What is coagulation of blood? Coagulation or clotting is the process by which blood forms clots. Clot: Clot is a gel-like mass formed by platelets and fibrin in the blood. Clotting factors and anticoagulants are made in the liver. They have the ability to turn on or turn off as needed.  What is embolism? An embolism is the sticking of an embolus in blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), or foreign material.  What is Thrombosis? Coagulation or clotting of the blood in a part of the circulatory system is thrombosis. Thrombosis is the formation or presence of a blood clot in a blood vessel. The vessel may be any vein or artery as, for example, in a deep vein thrombosis or a coronary (artery) thrombosis. The clot itself is termed a thrombus.  Important to know Prothrombin: Prothrombin is a protein produced by the liver. Prothrombin is present in blood plasma that is converted into active thrombin by a clotting factor known as factor X or prothrombinase during coagulation. Function of Thrombin: it is an enzyme that causes the clotting of blood by converting fibrinogen to fibrin Prothrombin activator: Prothrombin activator is a complex of coagulation factors that functions in catalyzing prothrombin into thrombin Fibrinogen: Fibrinogen is the major plasma coagulation factor Antithrombin: it is a small protein molecule that inactivates several enzymes of the coagulation system. (Factors IIa, IXa, Xa).  Stages of Blood Clotting In general, blood clotting occurs in three stages: 1. Formation of prothrombin activator 2. Conversion of prothrombin into thrombin 3. Conversion of fibrinogen into fibrin. Stages of blood coagulation  Anticoagulants (Heparin, Warfarin, Rivaroxaban) Anticoagulants are those substances which prevent coagulation of blood. Anticoagulants are of three types: 1. Anticoagulants used to prevent blood clotting inside the body, i.e. in vivo (In the living organism). Eg , warfarin 2. Anticoagulants used to prevent clotting of blood that is collected from the body, i.e. in vitro. 3. Anticoagulants used to prevent blood clotting both in vivo and in vitro. Eg heparin Anticoagulants and antiplatelet agents are medicines that reduce blood clotting in an artery, a vein or the heart. In vitro anticoagulants: those that remove calcium ions from the blood to prevent coagulation, such as citrate, oxalate, fluoride, and ethylene diamine tetra acetic acid (EDTA)  Heparin Heparin is a naturally produced anticoagulant in the body. It is produced by mast cells and basophils. Mechanism of Action of Heparin: It prevents blood clotting by its antithrombin activity. It directly suppresses the activity of thrombin (Combines with antithrombin III (a protease inhibitor present in circulation) and removes thrombin from circulation). Heparin is enhancing the activity of the endogenous inhibitor “antithrombin” by 1000 x. Mechanism of action of heparin  Heparin Pharmacokinetics Absorption and Distribution: Because of its polarity and large size, heparin is unable to cross membranes, including those of the GI tract. Consequently, heparin cannot be absorbed if given orally, and therefore must be given by injection (IV or subQ). Since it cannot cross membranes due to low molecular weight, heparin does not traverse the placenta and does not enter breast milk. Metabolism and Excretion: Heparin undergoes hepatic metabolism and excreted through renal route. Under normal conditions, the half-life is short (about 1.5 hours). However, in patients with hepatic or renal disease, the half-life is increased.  Adverse Effects and Contraindications(‫)تاداضت‬ Hemorrhage: bruises, petechiae, hematomas Heparin-Induced Thrombocytopenia Precautions: hemophilia, increased capillary. permeability, peptic ulcer disease Contraindicated: Heparin is contraindicated for patients with thrombocytopenia Activated partial thromboplastin time (aPTT). (normal range is 30-40 seconds) PT (prothrombin time) range is 11 to 14 seconds  Heparin—Clinical Applications Prophylaxis and treatment of Venous thrombosis (Deep vein thrombosis-DVT) Pulmonary Embolism(PE) Peripheral arterial embolism Prevention of post-op DVT/PE Treatment of DIC?? Prevention of clotting in surgery Anticoagulant in blood transfusions and dialysis Note: Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body blocking small blood vessels  Protamine Sulfate for Heparin Overdose 1 unit of heparin means the amount of heparin that will prevent 1 mL of sheep plasma from coagulating for 1 hour Antidote of heparin: Protamine sulfate Protamine sulfate is an antidote to severe heparin overdose. Protamine is a small protein that has multiple positively charged groups. These groups bond ionically with the negative groups on heparin Dosage of protamine is based on the fact that 1 mg of protamine will inactivate 100 units of heparin. Hence, for each 100 units of heparin in the body, 1 mg of protamine should be injected.  Nursing Considerations The nurse obtains baseline vital signs and physical assessment. He/she must obtain laboratory results of the complete blood count (i.e. CBC test), platelet count and activated partial thromboplastin time (aPTT), and clotting time. Monitor signs of bleeding- hematuria, epistaxis, ecchymosis, Hypotension and occult blood in stool Have available ANTIDOTE for heparin- PROTAMIME SULFATE Instruct the client not to use any “over the counter drug” without notifying the physician.  Factor X inhibitor “Rivaroxaban 2007” Rivaroxaban is an anticoagulant taken orally Indicated for prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing knee or hip replacement surgery. MOA: Rivaroxaban inhibits both free Factor Xa and Factor Xa bound in the prothrombinase complex Inhibition of Factor Xa interrupts the intrinsic and extrinsic pathway of the blood coagulation cascade, inhibiting both thrombin formation and development of thrombi.  Factor X inhibitor Rivaroxaban 2007 Adverse effects – Thrombocytopenia (low platelets count in the blood) – Retroperitoneal hemorrhage – Hypersensitivity – Cerebral hemorrhage  Why new born babies are given Vitamin K? Newborns are prone(‫ )راکش‬to vitamin K deficiency because… 1. Vitamin K is not easily transported across the placental barrier 2. Prothrombin synthesis in the liver is an immature process in newborns, especially when premature. 3. The neonatal gut is sterile, lacking the bacteria that is necessary in Vitamin K synthesis. Secondary deficiencies may occur with use of antibiotics. Newborn infants receive a single dose of vitamin K at birth because of a sterile intestinal tract.  Warfarin Warfarin is an anticoagulant used to prevent clots. Vitamin K antagonists act only in vivo and have no effect on clotting if added to blood in vitro. Role of vitamin k: The clotting factors II (prothrombin) VII, IX and X are synthesized as inactive precursors (zymogens) in the liver. Vitamin K act as a Coenzyme for activation. Warfarin  Mechanism of action of warfarin Warfarin inhibits the vitamin K-dependent synthesis of clotting factors II, VII, IX and X. Warfarin acts as a substrate for Vit k epoxide reductase and inhibits the conversion of vitamin K epoxide to Vit. K hydroquinone Side effects of warfarin Severe bleeding, including heavier than normal menstrual bleeding. Hematuria Black or bloody stool. Blood in vomiting Blood in sputum.  Pharmacokinetics Warfarin is readily absorbed following oral dosing. Once in the blood, about 99% of warfarin binds to albumin. Warfarin molecules that remain free (unbound) can readily cross membranes, including those of the placenta and milk-producing glands warfarin has a long half-life (1.5 to 2 days)  Fibrinolytics Blood clot is defined as the mass of coagulated blood which contains RBCs, WBCs and platelets entrapped in fibrin meshwork. RBCs and WBCs are not necessary for clotting process. However, when clot is formed, these cells are trapped in it along with platelets. The trapped RBCs are responsible for the red color of the clot. Fibrinolysis: Lysis of blood clot inside the blood vessel is called fibrinolysis. It helps to remove the clot from lumen of the blood vessel. Fibrin clot  Fibrinolysis Lysis of blood clot inside the blood vessel is called fibrinolysis. It helps to remove the clot from lumen of the blood vessel. This process requires a substance called plasmin or fibrinolysin. Plasmin is formed from inactivated plasminogen. Plasminogen is synthesized in the liver. Plasminogen is converted into plasmin by tissue plasminogen activator(tPA). It is a protein involved in the breakdown of blood clots.  Formation of Plasmin Plasmin is formed from inactivated glycoprotein called plasminogen. Plasminogen is synthesized in liver Plasminogen is converted into plasmin by plasminogen activator called urokinase plasminogen activator (u-PA). It is derived from blood.  Fibrinolytics or Thrombolytic drugs Alteplase Reteplase Anistreplase Streptokinase Urokinase  Mechanism of action of fibrinolytics Plasmin is produced in the blood to break down fibrin, the major constituent of blood thrombi, thereby dissolving clots once they have fulfilled their purpose of stopping bleeding. Fibrinolytics i.e. streptokinase activate plasminogen to produce plasmin. And plasmin then break down fibrin  Side effects Besides risk of serious internal bleeding, other possible risks include: Bruising or bleeding at the access site Damage to the blood vessel. Migration of the blood clot to another part of vascular system.  Antiplatelets (aspirin, clopidogrel, and Prasugrel) Antiplatelets are a group of medicines that stop blood cells (called platelets) from sticking together and forming a blood clot.  Basic steps Prothrombin activator --> Prothrombin --> Thrombin --> Fibrinogen --> Fibrin Platelets activation: increase expression of glycoprotein IIb/IIIa (GPIIb/IIIa, also known as integrin). What increase the above? Answer: Thromboxane A2, ADP (adenosine diphosphate), and thrombin. Platelet activation step's  Adenosine diphosphate Under normal conditions, platelets circulate in the blood freely and without interaction with one another. ADP is stored in inside platelets and is released upon platelet activation. ADP interacts with a family of ADP receptors found on platelets (P2Y12) which leads to platelet aggregation.  What is thromboxane A2? Thromboxane A2 is a type of thromboxane that is produced by activated platelets and has prothrombotic properties It stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by increasing expression of the glycoprotein complex GPIIb/IIIa.  What is thromboxane? Thromboxane is a member of the family of lipids known as eicosanoids(lipids) Thromboxane-A synthase, an enzyme found in platelets, converts the arachidonic acid to thromboxane-A2 which activate aggregation of platelets by increasing the expression of the glycoprotein complex GPIIb/IIIa.  How do Clopidogrel and Aspirin act as antiplatelete? Clopidogrel acts by inhibiting the ADP receptor on platelet cell membranes. The drug specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor, which is important in activation of platelets and cross-linking by the protein fibrin. Aspirin in lower doses(75-150 mg) exert antiplatelet effect by prevent the synthesis of thromboxane A2 by inhibiting Thromboxane-A synthase. Glycoprotein IIb/IIIa Receptor Antagonists The GP IIb/IIIa antagonists cause reversible blockade of platelet GP IIb/IIIa receptors, and thereby inhibit the final step in aggregation As a result, these drugs can prevent aggregation stimulated by all factors, including collagen, TXA2, ADP, thrombin, and platelet activation factor. DRUGS: Abciximab, Tirofiban (aggrastat),  Side Effects Headaches or dizziness. Nausea. Diarrhea or constipation. Indigestion (dyspepsia) Stomach ache or abdominal pain. Nose bleeds. Increased bleeding Tranexamic acid  Mechanism Tranexamic acid is an antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin  Tranexamic acid indications Tranexamic acid: it is used to treat or prevent excessive blood loss from major trauma, post partum bleeding, surgery, tooth removal, nose bleeds (epistaxis)  References Karch, A. M., & Karch. (2011). Focus on nursing pharmacology. Wolters Kluwer Health/Lippincott Williams & Wilkins. [Link] Katzung, B. G. (2017). Basic and clinical pharmacology. McGraw-Hill Education. Lehne, R. A., Moore, L. A., Crosby, L. J., & Hamilton, D. B. (2004). Pharmacology for nursing care. Smeltzer, S. C., & Bare, B. G. (1992). Brunner & Suddarth’s textbook of medical-surgical nursing. Philadelphia: JB Lippincott Mnemonic for coagulation factors