coagulation therapy.pdf

COAGUL ANTS P R E PA R E D B Y : DR. RAMA MAHRAN L E C T U R E R O F P H A R M A C O L O G Y, F O M S C U R A M A I B R A H I M @ M E D. S U E Z. E D U. E G WHAT HAPPENS WHEN YOUR FINGURE GETS INJURED? BLOOD COAGULATION FIBRINOLYTIC SYSTEM WHAT ARE COAGULANT...

COAGUL ANTS P R E PA R E D B Y : DR. RAMA MAHRAN L E C T U R E R O F P H A R M A C O L O G Y, F O M S C U R A M A I B R A H I M @ M E D. S U E Z. E D U. E G WHAT HAPPENS WHEN YOUR FINGURE GETS INJURED? BLOOD COAGULATION FIBRINOLYTIC SYSTEM WHAT ARE COAGULANTS? They are substances that promote coagulation. They are indicated in hemorrhagic disorders. Fresh whole blood or plasma contain all required coagulation factors.  Coagulants Systemic Local Non transfusional Transfusional Thrombin Vasoconstrictors Astringent Plasma Fractions Vit K Plasma, blood Desmopressin fibrinogen Fibrinolytic inhibitors  VITAMIN K Sources of vitamin K: 1. in diet especially in green leafy vegetables →Vitamin K1 (phytonadione 2. synthesized by bacteria living in human intestine Vitamin K2 (menaquinone) 3.Vitamin K3 is synthetic vitamin K that can be lipid soluble (menadione) or water soluble(menadione sodium bisulfate). Water soluble Vitamin K3 should not be used in practice (ineffective). MECHANISM OF ACTION Vit K acts as a cofactor at a late stage in the synthesis of prothrombin, factors VII, IX and X by liver. PHARMACOKINETICS OF VITAMIN K Vitamins K1, K2, and the lipid soluble form of Vit K3 are fat soluble that are absorbed from the intestinal tract. via lymph and require bile salts for absorption. Vitamin K1 is available clinically in oral and parenteral forms (SC forms are not preferred). Onset of effect is delayed for 6 hours but the effect is complete by 24 hours. It is metabolized in liver and the metabolites are excreted in bile and urine. INDICATIONS prevent the hemorrhagic disease of vitamin K deficiency in newborn babies. Treating Warfarin (anticoagulant drug) overdose. Treating Vitamin K deficiency resulting from: a. Obstructive jaundice and malabsorption. b. hospitalized patients in intensive care units because of poor diet. c. parenteral nutrition, recent surgery. d. multiple antibiotic therapy. e. Severe hepatic disease. SIDE EFFECTS OF VITAMIN K Vitamin K is well tolerated with very rare side effects. Anaphylaxis may occur following rapid IV infusion of emulsified vitamin K that may lead to death.  Coagulants Systemic Local Non transfusional Transfusional Thrombin Vasoconstrictors Astringent Plasma Fractions Vit K Plasma, blood Desmopressin fibrinogen Fibrinolytic inhibitors PLASMA FRACTIONS Concentrated plasma fractions and recombinant protein preparations of coagulation factors are available for the treatment of coagulation factors deficiencies. Fresh frozen plasma or whole blood is used for factor deficiencies for which no recombinant form of the protein is available Preparations of coagulation factors can be highly purified or intermediate purity lyophilized (freeze- dry) factors or recombinant preparations. These preparations are administrated intravenously. Which is safer? The administration of lyophilized preparations or recombinant preparations of coagulation factors? PLASMA FRACTIONS FOR HEMOPHILIA Factor VIII deficiency (hemophilia A) and factor IX deficiency (hemophilia B) can be prevented and treated by lyophilized human plasma concentrates or recombinant factors VIII or IX, respectively. Longer acting factor VIII and IX preparations: Eloctate is a factor VIII-Fc domain conjugate that prolongs the factor VIII half-life and administrated twice a week for the prophylaxis and treatment of hemophilia A. Idelvion is a factor IX-albumin conjugate with a half-life of 100 hours (native factor IX has a half-life of 16 hours) administrated once a week for the prophylaxis and treatment of hemophilia A. PLASMA FRACTIONS FOR TREATMENT OF BLEEDING ASSOCIATED WITH VON WILLEBRAND DISEASE Intermediate purity factor VIII concentrates contain significant amounts of von Willebrand factor. Humate-P is a factor VIII concentrate that is used for the treatment of bleeding associated with von Willebrand disease. Vonicog alfa is a recombinant Von Willebrand factor. PLASMA FRACTIONS CONT. Side effects of plasma concentrates can be: development of immune reactions against these concentrates → eg: hemophilia a or B with inhibitors. Recombinant factor VIIa is approved for treatment of inherited or acquired hemophilia A or B with inhibitors. Factor VIIa initiates activation of the clotting pathway by activating factor IX and factor X in association with tissue factor.  Coagulants Systemic Local Non transfusional Transfusional Thrombin Vasoconstrictors Astringent Plasma Fractions Vit K Plasma, blood Desmopressin fibrinogen Fibrinolytic inhibitors OTHER SYSTEMIC COAGULANT DRUGS Fibrinogen The fibrinogen fraction of human plasma is employed to control bleeding in haemophilia, factor VIII deficiency and acute afibrinogenemic states. Desmopressin acetate It is an analogue of vasopressin (antidiuretic hormone). increases the factor VIII activity of patients with mild hemophilia A or von Willebrand disease. It is administrated orally or intranasally. Adrenochrome monosemicarbazone Reduce capillary fragility, control oozing from raw surfaces and prevent microvessel bleeding,  Coagulants Systemic Local Non transfusional Transfusional Thrombin Vasoconstrictors Astringent Plasma Fractions Vit K Plasma, blood Desmopressin fibrinogen Fibrinolytic inhibitors  FIBRINOLYTIC INHIBITORS: AMINOCAPROIC ACID & TRANEXAMIC ACID Tranexamic acid: is an analog of aminocaproic acid and has the same properties. Mechanism of action: they are synthetic inhibitors of fibrinolysis. It competitively inhibits plasminogen activation. Pharmacokinetics: It is rapidly absorbed orally and is excreted by the kidney. CLINICAL USES OF AMINOCAPROIC ACID: As adjunctive therapy in hemophilia As therapy for bleeding from fibrinolytic therapy Treatment of Postsurgical gastrointestinal bleeding Vaginal bleeding Adverse Effects: Intravascular thrombosis from inhibition of plasminogen activator. hypotension, myopathy, abdominal discomfort, diarrhea, and nasal stuffiness.  Coagulants Systemic Local Non transfusional Transfusional Thrombin Vasoconstrictors Astringent Plasma Fractions Vit K Plasma, blood Desmopressin fibrinogen Fibrinolytic inhibitors LOCAL HAEMOSTATICS (STYPTICS) To help stop local bleeding eg: small injury the following is used: External bleeding is usually stopped by manual pressure, cotton-gauze pressure pack or by suturing. Local hemostatic that are substances used to stop bleeding from a local site. Examples of local hemostatic: 1. Thrombin obtained from bovine plasma may be applied to the bleeding surface in hemophiliacs. 2. Vasoconstrictors like 0.1% Adrenaline solution may be used to stop from bleeding tooth socket or nose in case of epistaxis 3. Astringents such as tannic acid or metallic salts are occasionally applied for bleeding gums, bleeding piles,