Thrombolytic agents work by activating plasminogen to form plasmin, which breaks down fibrin in blood clots. The document discusses several thrombolytic agents: streptokinase works by forming a complex with plasminogen to catalyze its activation; alteplase is a recombinant tissue plasminogen activator that selectively activates plasminogen bound to fibrin clots; and reteplase and tenecteplase are modified forms of tPA with longer durations of action. Thrombolytic agents are used to treat conditions caused by blood clots such as myocardial infarction, pulmonary embolism, and ischemic stroke.

1. THROMBOLYTIC
AGENTS

2.  Blood clots (thrombus/thrombi)
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 Vascular bed/Blood vessels
 Coronary thrombi cause myocardial infarctions
 cerebrovascular thrombi produce strokes
 pulmonary thromboemboli can lead to respiratory
and cardiac failure
 So it is important to rapidly diagnose and treat blood clots.

3.  Plasminogen, an inactive precursor
 It is converted to plasmin by cleavage of a single
peptide bond.
 Plasmin is a relatively nonspecific protease
 it digests fibrin clots and other plasma proteins,
including several coagulation factors.
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4. PLASMINOGEN
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PLASMIN
FIBRIN DEGRADATION PRODUCTS
CLOT DISSOLUTION
PLASMINOGEN
ACTIVATOR

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6.  Thrombolytic drugs dissolve blood clots by activating
plasminogen
 which forms a cleaved product called plasmin.
 Plasmin is a proteolytic enzyme that is capable of breaking
cross-links between fibrin molecules
 which provide the structural integrity of blood clots.
 Because of these actions, thrombolytic drugs are also called
"plasminogen activators" and "fibrinolytic drugs.”
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8. Clinical Uses of thrombolytic agents
 Acute Myocardial Infarction: administered by either the
intravenous or the intracoronary route for the reduction of
infarct size & congestive heart failure associated withAMI
 Pulmonary Embolism
 DeepVeinThrombosis
 ArterialThrombosis or Embolism
 Occlusion ofArteriovenousFistula
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13. Source:
 It is a protein produced by beta-hemolytic streptococci.
It has no intrinsic enzymatic activity.
MOA:
 It combines with proactivator plasminogen to form a
complex.
 This complex catalyzes the conversion of plasminogen
to active plasmin.
 So rapid lysis of the clot by plasmin.
 This complex also catalyzes the clotting factorV andVII.
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14. Plasma half life: (t ½)
12-18 minutes
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Adverse effects: Not clot specific.
◦ So can create a generalized lytic state when administered I/V.
and target
◦ Thus, both protective haemostatic thrombi
thromboemboli are broken down.
◦ Hemorrhage --- most serious cerebral hemorrhage
◦ Allergic reactions, rarely anaphylaxis and fever.
◦ The streptokinase-plasminogen complex is not inhibited by natural alpha 2-antiplasmin

15. Administration
 Acute ST-segment elevation myocardial infarction: The recommended dose for
streptokinase in the setting of acute ST-segment elevation myocardial
infarction is 1.5 million units intravenously over 30 to 60 minutes.
 Pulmonary embolism: The recommended dose in the setting of pulmonary
embolism is a loading dose of 250000 units intravenously over 30 minutes. This
is followed by 100000 units per hour for 24 hours.
 Deep vein thrombosis: The recommended dose in the setting of deep vein
thrombosis is a loading dose of 250000 units intravenously over 30 minutes.
This is followed by 100000 units per hour for 72 hours

16. Administration
 Arterial thrombosis or embolism: The recommended dose in the setting
of arterial thrombosis or embolism is a loading dose of 250000 units
intravenously over 30 minutes. This is followed by 100000 units per hour
for 24 to 72 hours.
 Arteriovenous cannula occlusion: The recommended course of treatment
for arteriovenous cannula occlusion is to instill 250000 IU of
streptokinase in a 2 mL solution into the occluded cannula.

17. Adverse effects
 Streptokinase can precipitate an allergic reaction. Symptoms include fever,
shivering, and rash.
 Patients in rare instances have developed nonfatal anaphylactic reaction
 In cases of anaphylaxis, patients should be administered adrenaline(0.5ml
of 1:1000 IM) immediately and discontinue streptokinase therapy
 The toxicity of streptokinase is believed to be because it is a polypeptide
derivative of beta-hemolytic streptococci bacteria.

19. A two chain serine protease containing 411 amino acid
residues isolated from cultured human kidney cells.
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It is an enzyme produced by the kidney, and found in the urine
MOA:
 It converts plasminogen to active plasmin.
 It is not clot specific:
◦ So can create a generalized lytic state when administered I/V.
◦ Thus, both protective haemostatic thrombi and target
thromboemboli are broken down.

20.  It is a tissue plasminogen activator (t.PA) produced by
recombinant DNA technology of 527 amino acids
 Mechanism:
 It is an enzyme which has the property of fibrin-enhanced
conversion of plasminogen to plasmin
 It produces limited conversion of free plasminogen in the absence
of fibrin
 When introduced into the systemic circulation it binds to fibrin in
a thrombus and converts the entrapped plasminogen to plasmin
followed by activated local fibrinolysis with limited systemic
proteolysis
Alteplase (rt.PA) 20

21. Pharmacokinetics:
It has very short t1/2 of 2-6 minutes
Side-Effects:
Bleeding including GIT & cerebral hemorrhage
Allergic reactions, e.g., anaphylactoid reaction, laryngeal
edema, rash, and urticaria have been reported very rarely
(<0.02%)
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Alteplase (rt.PA)

22. Acute Myocardial Infarction in adults for the improvement of
ventricular function following AMI the reduction of the incidence of
congestive heart failure, and the reduction of mortality associated with
AMI
Acute Ischemic Stroke for improving neurological recovery and
reducing the incidence of disability. Treatment should only be initiated
within 3 hours after the onset of stroke symptoms, and after exclusion
of intracranial hemorrhage
Pulmonary Embolism: Treatment of acute massive pulmonary
embolism
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23. Reteplase:
 Recombinant human t-PA. from which several amino
acid sequences have been deleted.
 Faster onset & slighter longer DOA.
 Less expensive
 Less fibrin specific than t-PA.
Tenecteplase:
 Mutant form of t-PA with a longer DOA.
 Slightly more fibrin-specific than t-PA.
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24. Conclusion
 Thrombolytic Agents are life saving drugs only when one knows
where, when and how to use these medications
 Risk:Benefit must be assessed in all patients