ANTI-COAGULANTS - cardiovascular drugs (part 6A/7)


Inhibit the co-agulation by inhibiting Thrombin or Vit K anatagonists

Heparin=Glycosaminoglycan…have negative charge…Acidic due to Sulphate & Carboxylicacid group….high moleculat weight…extracted from Porcine Intestinal Mucosa

Complexed with Histamine in Mast cells…Low molecular weigh heparin(LMWH)<6000

MOA=interact with AntiThrombin lll…speed up process of anti-coagulant ofn Antithrombin LMWH complex with Antithrombin & Inactivate Factor Xa…Prothrombin not convert into Thrombin…no formation of fibrin

Pharmacist medical student

T.E= used in Deep Vein Thrombosis…pulmonary embolism...Prophylactically in Pt. to avoid Postoperative thrombus during Elective surgery

Do not cross placenta...used in Pregnant women with Prosthetic heart valve

P.K=i.v administer...I/M inj leads to Hematoma formation…1-2hr t1/2…4hr of LMWH..

Titrate the infusion forr7-10 days so aPTT (activated Partial Thromboplastin time) b/w 1.5-2.5…. .taken up by Monocyte/Macrophage Sys for metabolismS.E= Hemorrhage...used Protamine sulphate, 1mg for 100 unit, weak antagonist….


Hypersensitivity reactions…risk of Thrombosis…Thrombocytopenia (abnormal Platelet) Osteoporosis...Contraindicated in surgery of brain,eye,spinal cord, in bleeding disorder 


Dabigatran=Prodrug...direct Thrombin inhibitor…first oral anticoagulant..used in Thromboprophylaxis in Orthopedic Surgery 

Lepirudin= Polypeptide...Similar to HIRUDIN derived from Leech Saliva..Produced in Yeast cell by Recombinant DNA technology…

Inhibit thrombin...diminish coagulation…bleeding major side effect

Argatroban= Directly inhibit Thrombin...used Prophylactically in Thrombosis in Pt with HIT 

Fondaparinux=Pentasaccharides...FDA approved Prophylaxis of Deep Vein 

Thrombosis in Hip or Knee surgery...long t1/2 17-21hr…contra in Renal Patients


Vitamin K Antagonists 

Co-agulation factor needs Vit K as a Co-factor for Coagulation… these factors undergo into Vit K residue of Glutamic acid… which Carboxylated into γ-CarboxyGlutamic acid… it bind to Ca++ ions… essential for Coagulation factor & platelet aggregation….. Vit K dependent Carboxylase fix CO2 to form COOH on Glutamic acid…… Reduced Vit K converted into Vit K Epoxide by Vit K Epoxide Reductase…


Warfarin=Coumarin anticoagulant...initially Rodenticide…


MOA= inhibit Vit K Epoxide Reductase which convert Reduced Vit K into Vit K Epoxide.... convert Glutamic acid residue into γ-CarboxyGlutamic acid….. 40hr t1/2


T.E= used in Deep vein thrombosis & pulmonary embolism …prevention of thromboembolism in orthopedic surgery or Gynecologic 


S.E=Skin lesion & necrosis…Black Boxwarning for Bleeding risk..Teratogenic cuase Abortion as well as Birth defects 


Thrombolytic drugs 

Streptokinase causes Systematic Fibrinolytic State...lead to bleeding problems Alteplase act locally on Thrombotic Fibrin to produce Fibrinolysis…

Urokinase produce in Kidney naturally, directly convert Plasminogen into Plasmin 

MOA= Directly or indirectly Convert Plasminogen into Plasmin..Cleave Fibrin, lysing thrombus….Clot dissolution & Reperfusion occur

T.E= used to dissolve clots in Stroke

S.E= Hemorrhage …Contraindicated in Healing wound, Pregnancy, Head trauma,

Brain tumor, Intracranial bleeding, Metastatic Cancer

Alteplase= known as Tissue Plasminogen Activator(tPA)…derived from Human Melanoma cell…product of Recombinant DNA..Called “Fibrin Selective”…used for M.I…Eteplase can be used as Alternative

S.E= GIT & Cerebral Hemorrhage occur Streptokinase=extracellular protein obtained from Group C β-Heemolytic Streptococci used for M.I within 4hr…t1/2 is 1hr…high Antigenicity

MOA= form complex with Plasminogen...this enzymatically active complex convert Plasminogen into Plasmin …Plasmin catalyze degradation of Fibrin, factor V &VII

S.E=bleeding, hypersensitivity

Anistreplase=complex of Plasminogen & Streptokinase Activator …..prodrug

Urokinase=in kidney …low antigenicity…

MOA= directly cleave Arginine-Valine bond of Plasminogen to yield plasmin

T.E=lysis of pulmonary emboli….off-label use is treatment of M.I, arterial thromboembolism, coornonry artery thrombus

S.E= anaphylactic reaction

DRUGS USED TO TREAT BLEEDING

Hemophilia=deficiency of plasma coagulation factor esp. VII & IX

Aminocaproic acid & Tranxamic acid= inhibit Plasminogen activation...Tranxamic acid 10 time more potent…intravascular thrombosis is side effect

Protamine Sulphate=Antagonize anticoagulant effect of Heparin...obtain from fish sperm/Testes…high in Arginine..+Ve charge…basic...S.E: Hypersensitivity reaction

Vitamin K= Vit K1 (Phytonadione)…used in immediate Homeostatsis...Fresh frozen plasma infusion…require 24 hr

Aprotinin=Serine Protease inhibitor...block plasmin...inhibit Streptokinase…used in patients at risk of blood loss during Coronort Artery Bypass…cause Renal Dysfunction

AGENTS USED TO TREAT ANEMIA

Anemia=below normal Plaasma Hb resulting from decreasing no. of RBCs or Abnormally low Total Hb 

Iron=known as Ferritin in Intestinal muscles...deficiency due to chronic blood loss, insufficient intake of iron during Accelerated growth in Childern & in heavily menstruating women…

Supplementation with Ferritin Sulphate….GIT disturbance reported

Folic Acid= used in Megaloblastic Anemia...Folinic acid/Leucovorin is reduced/active form of Vitamin B12 

Cyanocobolamine (Vit B12) =deficiency due to loss of Intrinsic Factor (GP produced by Parietal cells of stomach) OR loss of receptor in intestine 

Used in Pernicious Anemia….i.v or I/M,S/C used 

Erythropoietin & Darbepoetin= Erythropoietin produce in Kidney regulate RBS proliferation & Differentiation in Bone marrow….

Darbepoetin is long active form of erythropoietin…

Used in Anemia due to End-stage renal disease, HIV infection, Cancer Patient….HB level not> 12g/dl & dose not > 1g/dl

AGENTS USED IN SICKLE CELL ANEMIA 

Hydroxyurea=used to treat Chronic Myelogenous Leukemia, Polycythemia Vera….in Sickle cell Anemia drug increase Fetal HB level, diluting Abnormal HbS….

S.E= Bone marrow depression, Cutaneous Vasculitis 

Pentoxyfylline=methylxanthine derivative…called “Rheologic modifier”….improves RBC flexibility & reduce Viscosity…decrease total Peripheral Resistance…increase O2 

..Controlled or sustain release tab with food



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