Fibrinolytic drugs. Thrombosis and Thrombolytics. Activation of platelet aggregation. Mechanism of fibrinolytic drugs.

1. Fibrinolytic drugs.
Fibrinolytic drugs.
Presented by A. Gowtham Sashtha 1st M.pharm
Department of pharmacology
K.M College of pharmacy.
Madurai - 623 501.

2. Introduction:
> Thrombosis :
> ➜Thrombosis occurs when blood clots block
veins or arteries.
> ➜Complications of thrombosis can producing
such as a stroke or heart attack.
> Symptoms
> ➜Pain and swelling in one leg, chest pain, or
numbness on one side of the body.

3. Causes of Thrombosis :
→Endothelial injury
→Abnormal blood flow
→Hypercoagulability
Fibrinolytics (Thrombolytics)
Fibrinolytics(or) Thrombolytic is a agent to
treatment fo dissolve dangerous clots in blood
vessels, improve blood flow, and prevent damage to
tissues.

4. Normal Regulations of platelet aggregation:

5. Activation of
platelet
aggregation:

6. Formation of Fibrin :

7. Natures of Thrombus:

8. Fibrinolytics Drugs:
Plasminogen Activators:
I) 1st Generation:
→Streptokinase
→Urokinase
II) 2nd Generation:
→Anistreplase
→Alteplase
→Reteplase (analogue of Alteplase)
→Tenecteplas.

9. Mechanism of action of Fibrinolytics drugs:

10. Plasminogen Activators:
I) 1st Generation:
➜ Streptokinase:
Source:
→Streptokinase is a protein extracted from
cultures of beta hemolytic streptococci.
→It activates plasminogen
→No intrinsic enzymatic activity.

11. Mechanism of action:
➜ It combines with pro activators Plasminogen to
form a complex.
➜ This complex catalyst the conversation of
plasminogen to active plasmin.
➜So rapid lysis of the clot by plasmin.
➜ This streptokinase plasminogen complex in not
inhibited by natural a2-antiplastin.
➜ t1/2 - less than 20 mins

12. Adverse e ect:
➜ Hemorrhage
➜ Not used to steptococcal infections (Have anti
steptococcal antibodies may develop Hypersensitivity
reactions).
➜ Hypersensitivity due to antigenicity (rash, fever,
allergic reaction).
➜ Hypotension.

13. ➜ Urokinase:
Source:
➜It is an enzyme isolated from human urine but
commercially prepared from cultured human kidney
cells.
MAO:
➜It is not clot specific:
➜so can create a generalized lytic state when
administered I.V

14. ADR:
➜ Bleeding,
➜ Decreased hematocrit
➜ Chest pain,
➜ Increased heart rate,
➜ Fever,
➜ Chills,
➜ Nausea, vomiting,
➜ Anaphylaxis reactions.

15. II) 2nd Generation:
Anistreplase:
➜ It is a prodrug.
➜Anisolyated plasminogen Streptokinase
Activators Complex (APSAC).
MOA:
➜ In de-acylated in circulation into the
plasminogen-Steptokinase complex.
➜ t1/3 - 70-120 mins.

16. Advantages of Anistreplase:
➜ Longer duration of action than streptokinase
➜ More Thrombolytics activities than streptokinase.
➜ Greater clot selectively than Streptokinase.

17. Alteplase: (Recombinant tissue plasminogen activators
-(rt-PA) ).
Source:
➜It is isolated from recombinant DNA technology
from human tissue culture.
MAO:
➜ It is moderately specific for fibrin bound
Plasminogen.
➜ It is directly inactivated by Plasminogen activator
inhibitors - 1 (PAI-1).

18. ADR:
➜ Nausea,
➜ Mild hypotension,
➜ Fever may occur,
Reteplase:
➜ It is a modified from of rt-PA that is longer
duration of action.
➜ Same mechanism of Alteplase

19. Tenecteplase:
➜ It is another genetically modified human t-PA.
➜ And also prepared from recombinant DNA
technology.
➜ It is more fibrin specific & long duration than
alteplase.
➜ It has half life of more than 30 mins.
➜ It only approved for use in acute myocardial
Infarction.

20. Therapeutic uses of Fibrinolytics drugs:
1)Acute myocardial Infarction:
➜ Fibrinolytics are an alternative first line approach to
emergency percutaneous coronary intervention (PCI) with
stent placement.
➜ Both 1st and 2nd generation drugs are used.
2)Deep vein thrombosis:
➜In leg, pelvis, shoulder.
➜Up to 60% patients can be successfully treated.
➜The Fibrinolytics drugs are decrease the pain and
swelling. Streptokinase,urokinase, alteplase.

21. 3) Pulmonary embolism:
➜ Fibrinolytics therapy is indicated in life saving
drugs of Pulmonary Embolism.
➜ The Fibrinolytics drugs lung function is better
preserved.
➜ The Fibrinolytics recanalise 40% of lumb artery
occlusion, especially those treated within 72 hr.

22. 5) Stroke:
➜ Thrombolytics therapy of ischaemic stroke
contraversial.
➜ Possibility of improved neurological outcome is
to be balanced with risk of intra cranial haemorrhage.
➜ Now alteplase is approved for use in ischaemic
strock

24. THANK YOU

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