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    Thrombolytics (Fibrinolytics)

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    J lodhi
    Thrombolytics such as streptokinase, urokinase, and tissue plasminogen activators work to break down blood clots. Streptokinase works by forming a complex with plasminogen to generate plasmin, while tissue plasminogen activators like alteplase selectively activate plasminogen bound to fibrin in clots. These thrombolytics are used to treat pulmonary embolism, deep vein thrombosis, myocardial infarction, and peripheral vascular disease when administered intravenously or intra-arterially. Potential adverse effects include bleeding, allergic reactions, and hypotension.

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    Thrombolytics (Fibrinolytics)

    Uploaded by

    J lodhi
    331 views14 pages
    Thrombolytics such as streptokinase, urokinase, and tissue plasminogen activators work to break down blood clots. Streptokinase works by forming a complex with plasminogen to generate plasmin, while tissue plasminogen activators like alteplase selectively activate plasminogen bound to fibrin in clots. These thrombolytics are used to treat pulmonary embolism, deep vein thrombosis, myocardial infarction, and peripheral vascular disease when administered intravenously or intra-arterially. Potential adverse effects include bleeding, allergic reactions, and hypotension.

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    Thrombolytics such as streptokinase, urokinase, and tissue plasminogen activators work to break down blood clots. Streptokinase works by forming a complex with plasminogen to generate plasmin, while tissue plasminogen activators like alteplase selectively activate plasminogen bound to fibrin in clots. These thrombolytics are used to treat pulmonary embolism, deep vein thrombosis, myocardial infarction, and peripheral vascular disease when administered intravenously or intra-arterially. Potential adverse effects include bleeding, allergic reactions, and hypotension.

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    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
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    331 views14 pages

    Thrombolytics (Fibrinolytics)

    Uploaded by

    J lodhi
    Thrombolytics such as streptokinase, urokinase, and tissue plasminogen activators work to break down blood clots. Streptokinase works by forming a complex with plasminogen to generate plasmin, while tissue plasminogen activators like alteplase selectively activate plasminogen bound to fibrin in clots. These thrombolytics are used to treat pulmonary embolism, deep vein thrombosis, myocardial infarction, and peripheral vascular disease when administered intravenously or intra-arterially. Potential adverse effects include bleeding, allergic reactions, and hypotension.

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    © All Rights Reserved
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    of 14

    Thrombolytics

    (Fibrinolytics)
    Thrombolysis (Fibrinolysis)
    (A). Natural:-
    • • Plasminogin- Plasmin syst:-
    Plasminogen:-
    • » A serum β-globulin
    • » Deposited in fibrin strands in thrombus
    • » Plasminogen activators with short t ½ in circulation
    diffuse in thrombus → cleave Arg - Valine bond →
    release plasmin
    (B). Exogenous:-
    (a). Streptokinase:-
    » Non enzymatic protein
    » Derived from culture of β-Haemolytic st.cocci
    » Biologically assayed & standardized
    » Oldest agent with long history of use
    » Being of Bact. Origin → Antigenic
    • MOA
    » Combine with proactivator plasminogen& form
    complex.
    ↓
    Plasminogen→ Plasmin
    » Plasmin formed in thrombus protected from anti
    plasmin
    Adverse Effects
    In Pts. with Anti-Str-coccal anti-bodies:-
    • Fever
    • Allergic Reaction
    • Therapeutic Resistance
    • ↑ Risk of Bleeding→ Lysis of Fibrin & fibrinogen
    • Cause burst of plasmin → generates kinins →
    Hypotension
    Administration
    • Given I/V
    • Can be given by I / Vas. Catheter for local eff.
    Monitoring
    • Thrombin time
    Urokinase
    » More costly
    Produced naturally in the body
    » Human enz → isolated from urine
    » Synth. by Human embryonic kidney cells in culture
    » Recently by genetic engineering (rDNA technology in
    bacteria)
    MOA
    » Having enzymatic activity → acts directly
    » Converts plasminogen → plasmin
    » Plasmin formed in thrombus protected from anti
    plasmins
    » Non Anti-genic
    » Highly specific
    Uses
    » Systemic thrombolytic therapy
    » MI
    Human- Tissue plasminogen
    activator (t-PA)
    • Synthesize by endoth. Cells in body
    • Manufactured by rDNA –tech
    » Alteplase
    » Tenecteplase
    » Duteplase
    » Reteplase
    MOA
    • Clot selective action (Activity ↑ in the presence of fibrin)
    • Selectively act on fibrin bound plasminogen
    • Restrict action of plasmin to thrombus
    • Avoid syst. Activation or Min. syst. Activation
    • Min. Eff. on circulating fibrinogen. C / W St. & Urokinase.
    • Extremely expensive
    • Given I/V
    Uses:
    coronary thrombosis.
    Anistreplase: (Anisoylated plasminogen - St. kinase activator
    complex)(APSAC)
    • Complex of purified human lys plasminogen & bact. St.
    kinase which has been acylated to protect active
    enzymatic site. ( By para-anisoyl gp)
    MOA
    • When adm acyl group undergoes spon. hydrolysis.
    • Activated st. kinase proactivator complex freed
    • Has greater clot selectivity
    • More thrombolytic activity

    Administration
    • Given by single I/V Inj of 30 units over 3 - 5 min
    • Followed by heparin & then warfarin
    Adv. eff of fibrinolytic agents
    • Bleeding.

    Treated with
    o Aminocaproic acid
    o Tramexanic acid
    o Fresh whole blood.

    • Allergic reactions. (st. kinase)


    Contra –Indication
    » Active Bleeding
    » C. V. A
    » Pts Undergoing Surg
    Uses of Fibrinolytics
    (a). I/V Route:-
    • Multiple pulmonary emboli. (Not Massive enough
    necessitating surgery)
    • Central DVT involving:
    » S.V.C Syndrome
    » Ascending Theombophlebitis of ileofemoral
    vein.
    •MI
    (b). I/ART:-
    • Peripheral vascular Dis
    Treatment of Ac. MI
    (a)-t-PA
    » I/V infusion of 60 mg over 1st hr.
    » Then 40 mg at a rate of 20 mg/ hr
    (b)- St.Kinase
    » I/V infusion-loading dose 250,000 units.
    » Followed by 100,000 units/ hr for 24 - 72 hrs
    » Can also be given by I / Coronary catheter for
    local effect
    (c)-Urokinase:-
    » I/V infusion loading dose 300,000 units given over 10
    Min
    » Maint. Dose 300,000 units / HR for 12 HRs
    (d)-Anistreplase:-
    » Single I/V inj of 30 units over 3-5 min

    (e)-Anti-Coagulant:

    (f)-Anti-platelet agents:

    (g)-b-Blockers:
    • After 1st attack of MI:
    o Prevent arrythmias
    o Prevent reinfarction
    • Timolol is usually recommended

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