this ppt about the thrombolytic agents and its mechanism of action, uses, adverse effects and contraindications. this will help to the medical students to understand about the fibrinolytic drugs easily

1. A 58 year old male came to the emergency
department with complaints of left sided chest pain
radiates to the back and left arm and increased
sweating, difficulty in breathing since 4 a.m today.
He is a known hypertensive and diabetic for past 10
years under regular treatment,
what is your diagnosis ?
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2. ACUTE MYOCARDIAL
INFARCTION
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3. 3

4. By the end of the session will be able to
 Understand what is Fibrinolytic system
 Describe the fibrinolytic drugs & its mechanism
 Enlist its Uses & Adverse effects
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5. Checks and balances the clotting system
Dissolves the clot at the site of damage, once
damage is repaired
Activators : tPA, Factor XIIa & Kallikrein
Inhibitors : α2 anti plasmin, α2 macroglobulin
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6.  Plasmin :
○ Enzyme responsible for fibrin degradation
○ Generated from plasminogen by tPA (tissue
plasminogen activator)
 Plasminogen :
○ Inactive form of plasmin
○ Present in circulation as well as bound to fibrin
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7.  tPA (tissue Plasminogen Activator) :
○ Produced by vascular endothelium
○ Selectively activates fibrin bound plasminogen
into plasmin
 Anti plasmin :
○ Present in circulation and inactivates the leaked
plasmin & prevents premature lysis of fibrin
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8. 9
PLASMINOGEN PLASMIN
Fibrin (Soluble)
Fibrin (Insoluble)
Extrinsic activators :
Fibrinolytic drugs
Eg.: Streptokinase,
Alteplase
Intrinsic activators:
tPA, Factor XIIa,
Kallikrein

9.  Streptokinase
 Urokinase
 Alteplase
 Reteplase
 Tenecteplase
 Antistreplase
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10.  Obtained from β hemolytic streptococci
MOA :
Forms 1:1 complex with plasminogen
Catalyses
1. Plasminogen(Inactive)  Plasmin(active)  Fibrinolysis
2. Breakdown of fibrinogen
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11.  Non fibrin specific
 Half life : 60 – 80 mins
Use : Myocardial infarction, Deep vein thrombosis &
Pulmonary embolism
Advantages :
 Least expensive ; still used in resource poor areas
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12. Disadvantages :
 Antigenic ; can cause hypersensitivity
 Anti streptococcal antibodies – reduce its efficacy
 Cannot be repeated
 Fever, Hypotension, arrhythmia
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13.  Cultured from human kidney cells
 Direct plasminogen activator
 Can degrade both fibrin & fibrinogen
 T1/2 : 20 mins
Use :
 Patients whom streptokinase cannot be repeated
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14. Advantages :
 Mild fibrin specific
 Non antigenic ; Non pyrogenic ; does not produce
hypotension
 Pro urokinase : recombinant form ; more fibrin
specific
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15.  Recombinant tissue plasminogen activator
 Produced by recombinant DNA technology from
human tissue culture
 More fibrin specific ; hydrolyze fibrin only (not
fibrinogen)
 Rapidly activates plasminogen ; t1/2 is 5–10 mins
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16. Advantages :
 Non antigenic
 Superior in dissolving old clots
Disadvantages :
 Higher incidence of reocclusion ; needs I.V heparin
co administration
 Fever, Nausea, mild hypotension
 Quite expensive
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17.  Modified recombinant tissue plasminogen activator
 Less specific for fibrin bound plasminogen
 Long acting ; t1/2 is 15 – 20 mins
 Dose : 10 mg over 10 min repeated after 30 min
 A/E : fever, hypotension
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18.  Genetically engineered mutant form of native rt-PA
 IV single bolus dose 50mg over 10 seconds
Advantages :
 High fibrin selectivity
 Long acting ; t1/2 is 2hours
 Resistance to PAI –1 (plasminogen activator inhibitor 1)
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19. Disadvantages :
 Very expensive
 Risk of cranial bleeding
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20.  Anisolyated plasminogen streptokinase activator
complex
 Consists of purified human plasminogen with
bacterial streptokinase in which the active site of
plasminogen has been protected by anisoylation (a
process of acetylation)
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21.  Mechanism :
Administration
Acyl group hydrolyses spontaneously
Release the streptokinase – proactivator complex
fibrinolysis
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22. Advantages :
 Synthesized to improve the pharmacokinetics of
streptokinase-proactivator complex
 More fibrin specificity
 Long acting (t1/2 > 90mins)
 A/E : Hypersensitivity, Hypotension, Bleeding etc.
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23.  Acute Myocardial Infarction
 Deep Vein Thrombosis
 Pulmonary embolism
 Peripheral arterial occlusion
 Stroke 24

24.  Intracranial haemorrhage /
Intracranial tumour
 Ischemic stroke / Head injury
in past 3 months
 Vascular abnormalities
 Bleeding disorders
 Peptic ulcer
 Esophageal varices
 Any wound or recent fracture
 Tooth extraction
 Major surgery within 3 weeks
 Uncontrolled hypertension
 Pregnancy
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25.  tPA – main activator of fibrinolytic system
 Streptokinase – antigenic ; non specific
 Urokinase – fibrin specific ; less side effects
 Alteplase – very short acting ; risk of reocclusion
 Reteplase – less fibrin specific ; long acting
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26.  Tenecteplase : High fibrin selectivity ; long acting ;
resistance to PAI 1
 Antistreplase : modified anisolyated streptokinase
to improve pharmacokinetics
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27. 10/17/2023
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