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    Thrombolytics & Antiplatelet Drugs

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    Dr.U.P.Rathnakar.MD.DIH.PGDHM
    The document discusses various drugs that affect blood coagulation and platelet function including fibrinolytics, antifibrinolytics, and antiplatelet drugs. It describes the mechanisms and properties of drugs like streptokinase, urokinase, alteplase, clopidogrel, aspirin, and abciximab. The text provides details on the indications, mechanisms of action, adverse effects and important points of these drugs used in management of conditions like myocardial infarction and thrombosis.

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    Thrombolytics & Antiplatelet Drugs

    Uploaded by

    Dr.U.P.Rathnakar.MD.DIH.PGDHM
    130 views40 pages
    The document discusses various drugs that affect blood coagulation and platelet function including fibrinolytics, antifibrinolytics, and antiplatelet drugs. It describes the mechanisms and properties of drugs like streptokinase, urokinase, alteplase, clopidogrel, aspirin, and abciximab. The text provides details on the indications, mechanisms of action, adverse effects and important points of these drugs used in management of conditions like myocardial infarction and thrombosis.

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    Theory class for MBBS

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    Thrombolytics & Antiplatelet drugs

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    The document discusses various drugs that affect blood coagulation and platelet function including fibrinolytics, antifibrinolytics, and antiplatelet drugs. It describes the mechanisms and properties of drugs like streptokinase, urokinase, alteplase, clopidogrel, aspirin, and abciximab. The text provides details on the indications, mechanisms of action, adverse effects and important points of these drugs used in management of conditions like myocardial infarction and thrombosis.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    130 views40 pages

    Thrombolytics & Antiplatelet Drugs

    Uploaded by

    Dr.U.P.Rathnakar.MD.DIH.PGDHM
    The document discusses various drugs that affect blood coagulation and platelet function including fibrinolytics, antifibrinolytics, and antiplatelet drugs. It describes the mechanisms and properties of drugs like streptokinase, urokinase, alteplase, clopidogrel, aspirin, and abciximab. The text provides details on the indications, mechanisms of action, adverse effects and important points of these drugs used in management of conditions like myocardial infarction and thrombosis.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 40

    Fibrinolytics, antifibrinolytics and antiplatelet drugs

    Dr.Rathnakar U.P
    MD.DIH.PGDHM
    www.scribd.com

    Blood coagulation

    Two contrasting properties of Blood


    Remains fluid in circulation Solidifies when vessels are

    injured Mechanism is complex and

    Vascular Phase

    Platelet Phase
    Coagulation Phase Fibrinolytic Phase

    1. Anticoagulant
    Parenteral

    Heparin

    Inactivation of clotting factors

    DVT

    Oral

    Warfarin

    Decrease synthesis of clotting factors Decrease platelet aggregation


    Fibinolysis

    DVT
    Prevent arterial thrombosis Breakdown of thrombi

    2. Antiplatelet

    Aspirin

    3. Thrombolytic Streptokinase
    4

    EXTRINSIC Streptokina se Urokinase Rt-PA

    Activators

    INTRINSIC Factor XIIA Kallikrein T-PA

    Fibrin [Insoluble]

    PLASMINOGEN
    [Circulating&Fibrin]

    Activated to
    PLASMIN

    EACA Tranexaemic acid Aprotinin EXTRINSIC


    5

    Inhibitors

    2Antiplasmin 2Macroglobul in INTRINSIC

    Fibrin [Soluble]

    Fibrinolytic system

    Fibrinolytics

    Streptokinase and Urokina


    Alteplase Reteplase Tenecteplase Anisstreplace [Anisoylated purified streptokinase activator complex]

    Source
    Alteplase Reteplase Recombinant Recombinant

    MOA [PA]
    Fibrin specific As above

    Antigen Route[i.v.] ic
    No No i.v. i.v.

    ADE
    Less Less

    Tenecteplas e Streptokina se

    Recombinant Streptococci

    As above Plasminoge n complex Non-specific


    Destroyed by AB

    NO YES

    i.v. i.v.

    Less High

    Urokinase

    Human urine/Recombinant

    Directly acts, [Not as complex] Not Destroyed by AB No need to form

    NO

    i.v.

    Less

    7 Anistreplas e

    Synthetic Plasminogen+SK

    YES

    i.v.

    High

    Charecteristi c
    t1/2[Minutes]

    Streptokinas e
    30-80

    Urokinase

    Alteplase

    15-20

    4-8

    Fibrin specificity

    Minimal

    Moderate

    Maximum

    Plasminogen Binding Antigenicity

    Indirect

    Direct

    Direct

    Yes

    No

    NO

    Dose

    1.5 MU

    3-4 MU 3L.i.v-10mts 3L/h-12h

    100mg 15mg bolus 50mg-30mts

    Administration

    1.5MU i.v.

    General properties-Thrombolytic agents


    MOAAll are activators of plasminogen PKAdministered by i.v. route USEMI is the most important use WhenTo be given in the therapeutic window-6

    hours ADE Some are highly antigenic Hemorrhage is the most important

    FibrinolyticsAdverse effects

    10

    Streptokinase

    ADEs Bleeding Antigenic-Anaphylaxis, Rashes

    Streptokinase.

    Therapeutic uses: Acute myocardial infarction, Acute pulmonary embolism, Deep-vein thrombosis, Arterial thrombosis [PVD],

    12

    Urokinase.
    Isolated from human? Directly acts on plasminogen Non-antigenic. Adverse action profile same SK
    13

    Alteplase
    Alteplase (tPA) originally derived from cultured human

    melanoma cells-now recombinant DNA technology. Mechanism of action: Alteplase has a low affinity for free plasminogen in the plasma-rapidly activates plasminogen that is bound to fibrin in a thrombus or a hemostatic plug. Fibrin selective-At low doses, it has the advantage of lysing only fibrin, without unwanted degradation of other proteins- fibrinogen. Streptokinase, which acts on free plasminogen and induces a general fibrinolytic state. [Note: At therapeutic doses, circulating plasminogen may be activated, resulting in hemorrhage.]

    15

    Anistreplase
    Anisoylated plasminogen streptokinase

    activator complex Anistreplase is a preformed complex of streptokinase and plasminogen and it is considered to be a prodrug.

    Fibrinolytics-Indications
    Acute MI

    Acute Ischemic Stroke


    Deep Vein Thrombosis Pulmonary embolism Peripheral arterial occlusion Administration-STEMI Within 1 hr[golden hour] Not useful after 6 hours of MI[Th.window] Bleeding risk same with all.

    Fibrinolytics-CI
    AbsoluteContraindicatio

    ns 1. Prior ICH 2. Known Cerebral vascular lesion 3. IC malignant neoplasm 4. Ischemic stroke-past 3 months 5. Aortic dissection 6. Active bleeding,bleeding diatehsis[Not menstruation]

    Relative Contraindications 1. Poorly controlled/sever HTN 2. Major surgery-3 weeks 3. Recent internal bleeding 4. SK/Anistreplase-h/o allergy/prior admn. 5. Pregnancy 6. Active peptic ulcer

    Uses of Antifibrinolytics

    ADEs Antifibrinolytics

    Summary: Fibrinolytics

    Antiplatelet drugs

    Platelet-Adhesion-activation-aggregation

    Vascular injury, von Willebrand factor binds to collagen in the exposed subendothelium at the site of injury. The other site of the rod-formed von Willebrand factor binds to the platelet receptor GPIb and platelets are thereby anchored to the site of the

    Activation
    5HT, ADP

    Attach to nearby platelets and activate


    TXA2

    TXA2 [-]

    ATP

    cAMP

    [+] DAG,IP3

    [-]Aspirin

    COX1

    Arachidonic acid

    []Dipyridamole 5AMP
    PGI2 Epoprostenol Receptors

    Endothelium

    Collagen+vW Factor

    Aggregation

    [-]Aspirin [GPIIb/IIIa ]Dipyridamole


    Epoprostenol Fibrinoge n ADP P2Y1&P2Y12 Clopidogrel Abciximab-Eptifibatide-Tirofiban

    GPIIb/IIIa

    Aggregation Vasoconstrict TXA2 ion Atherosclero


    Terutroban

    Ticlopidine

    The role of platelets

    Platelet cox-1 inhibitor P2y12[Adenosine] receptor blockade

    Aspirin Ticlopidine, Clopidogrel , Prasugrel, Elinogrel, Ticagrelor

    GPIIb/IIIa antagonist
    Phosphodiesterase inhibitor

    Abciximab, Eptifibatide, Tirofiban


    Dipyridamole, Pentoxifylline, Cilostazole

    Thrombaxane A2 synthesis GR3219 inhibitor Natural platelet aggregation inhibitor PGI2 [Epoprosteno]l, nitric oxide

    ASPIRIN
    Mechanism of action: Aspirin (acetylsalicylic acid) irreversibly inhibits cyclooxygenase-1 in platelets Blocks the formation of thromboxane A2 (TXA2; a potent vasoconstrictor and platelet aggregant). Only the parent form, acetylsalicylic acid, which has any significant effect on platelet function.

    Aspirin
    Platelets are unable to regenerate cyclooxygenase, antithrombotic effect of aspirin remains for the lifespan of the platelet (810 days). After stopping aspirin therapy, normal haemostasis may be regained when about 20% of platelets have normal cyclooxygenase activity, daily aspirin intake is recommended

    Aspirin-ADE
    Adverse effects
    Dyspepsia Erosive gastritis Peptic ulcer with bleeding and perforation Hepatic and renal toxicities Increase in bleeding tendency

    Aspirin-imp/points
    Aspirin in low dose inhibits cox-1 of platelets in liver 2. Platelets have no nuclei-hence no regeneration 3. Inhibition irreversible [Other NSAIDs reversible] 4.Higher doses inhibit PGI2 in vessel wall 5. Low dose-can produce peptic ulceration and bleeding 6. Aspirin resistance-Failure to respond.1.

    Platelet cox-1 inhibitor P2y12[Adenosine] receptor blockade

    Aspirin Ticlopidine, Clopidogrel , Prasugrel, Elinogrel, Ticagrelor

    GPIIb/IIIa antagonist
    Phosphodiesterase inhibitor

    Abciximab, Eptifibatide, Tirofiban


    Dipyridamole, Pentoxifylline, Cilostazol

    Thrombaxane A2 synthesis GR3219 inhibitor Natural patelet aggregation inhibitor PGI2 [Epoprosteno]l, nitric oxide

    P2Y12 receptor antagonist

    Drug interaction
    Synergestic effect on platelet with aspirin

    250mg twice daily orally

    P2Y12 receptor antagonist

    Clopidogrel
    Closely related to ticlopidine 75mg once daily, orally

    Less than

    Platelet cox-1 inhibitor P2y12[Adenosine] receptor blockade

    Aspirin Ticlopidine, Clopidogrel , Prasugrel, Elinogrel, Ticagrelor

    GPIIb/IIIa antagonist
    Phosphodiesterase inhibitor

    Abciximab, Eptifibatide, Tirofiban


    Dipyridamole, Pentoxifylline, Cilostazol

    Thrombaxane A2 synthesis GR3219 inhibitor Natural patelet aggregation inhibitor PGI2 [Epoprosteno]l, nitric oxide

    Glycoprotein IIb/ IIIa receptor antagonist


    ABCIXIMAB:

    A Monoclonal antibody MOA: Inhibition of this receptor blocks binding of fibrin to platelets and platelet aggregation
    USE: Used with Aspirin+Heparin during coronary artery interventions. i.v.infusion ADE: Bleeding, Thrombocytopinia, constipation

    Indications for antiplatelet drugs


    STEMI NON-STEMI
    Acute ischemic event Percutaneous Coronary Interventions

    Before During Procedure After MI Previous


    Previous stroke PVD LL Arterial graft CABG Carotid endarterectomies AF

    Acute ischemic stroke


    High risk of vascular events

    Revascularization procedures
    Prosthetic valves

    Usually with anticogulants

    Summary: Antiplatelets

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