Fibrinolytics.

In this slide you will get to learn about Fibrinolytics.

1. Fibrinolytics Presented by: Shaikh Nisar Ali ( M.Pharma ) Dept. of Pharmacology Guided by: Dr. Ashok Kumar Dastapur

2. Fibrinolysis : - T he process of dissolution of the C lot is called fibrinolysis . Fibrin : - Clot in the blood. Lysis :- Breakdown. Fibrinolysis :- Breakdown of fibrin clot. Fibrinolytics are the agents which help in fibrinolysis. They are used to lyse the thrombi/clot to recanalize the occluded blood( Mainly Coronory Artery)

3. MECHANISM OF FIBRINOLYSIS: - Plasminogen is the inactive precursor present in plasma. It is converted to Plasmin by an Activator Substance present in blood and tissues. Plasmin can break down clots. Plasminogen Plasmin Clot Dissolution. All fibri nolytic agents currently in use act directly or indirectly as plasminogen activators. They produce lyses of an already formed clot. So they are curative rather than prophylactic. They can be injected -> 1)I nt raarterially close to t hombus for a localised effect . 2)I ntravenously for a generalized effect in multiple Th rombi . Clobdj

4. USES : - Fibrinolytic agents are used in : Myocardial Infarction Pulmonary embolism Deep vein thrombosis Peripheral arterial occlusion Ischemic Stroke FIBRINOLYTICS AGENTS ARE: - Streptokinase Urokinase Tissue - Type Plasminogen Activator

5. STREPTOKINASE :- It is a fibrinolytic agent obtained from beta hemolytic Streptococc i. It acts as a plasminogen activator leading to fibrinolysis . It binds with circulating plasminogen to form complex that activates plasminogen to Plasmin. USES : - Acute Myocardial Infarction.( 7.5 – 15 lac IU I.V over 1 hr. Period.) Deep vein thrombosis. ( 2,50,000 Units I.V in 30 Minutes. Followed by 100000 units every hour for 24 to 72 hours. Pulmonary Embolism.

6. ADVERSE EFFECTS: - It is Antigenic and so produces hypersensitivity reactions. It produce local irritation and dangerous haemorrhage. It produce fever. Bleeding. Hypotension. Arrythmias.

7. Streptokinase

8. UROKINASE: - It is an Enzyme prepared from human urine. It is now prepared from cultured human kidney cells. Unlike Streptokinase It is :- Non – Antigenic Non- Pyrogenic Does not produce Alergic reactions. Is is Expensive.

9. Urokinase

10. TISSUE – TYPE PLASMINOGEN ACTIVATOR :- It is a natural protein in man. It is prepared by Recombinant DNA technology. It has a selective effect on plasminogen bound to fibrin clot. Systemic activation of plasminogen and so bleeding is minimised. So it is safer than streptokinase.

11. Alteplase

12. Anti-Platelets Drugs An  antiplatelet drug  ( antiaggregant ), also known as a  platelet agglutination inhibitor  or  platelet aggregation inhibitor , is a member of a class of  pharmaceuticals  that decrease  platelet aggregation  and inhibit  thrombus  formation. They are effective in the  arterial  circulation, where  anticoagulants  have little effect. They are widely used in primary and secondary prevention of thrombotic cerebrovascular or cardiovascular disease

13. FUNCTIONS OF PLATELETS: - Intravascular thrombosis is initiated by platelet adhesion and aggregation. Platelets stick to the damaged vessel wall (adhesion). Then they stick to each other (aggregation) and release adenosine diphosphate (ADP) and thronboxane A2 (TXA2). This promotes further aggregation and also fibrin formation (clot).

14. Antiplatelet drugs inhibit platelet aggregation. So they are useful in the prevention and treatment of thrombosis in conditions like myocardial infarction 2) myocardial ischemia 3) cerebral ischemia. Prostacyclin (PGI2) synthesised in blood vessels is a natural inhibitor of platelet aggregation.

15. Mechanism of Action of Anti-Platelet drugs

16. Anti - platelet drugs classification TXA2 Synthesis Inhibitor : - ASPIRIN Phosphodiesterase Inhibitor : - DIPYRIDAMOL , CILOSTAZOLE Thienopyridine deeivatives (ADP Antogonist) : - TICLOPIDINE , CLOPIDOGREL GP-llb/llla Receptor Antagonist : - ABCIXIMAB , TIROFIBAN Others : - PGI2 , CLOFIBRATE

17. Aspirin :- Its is a Thromboxane A2 synthesis Inhibitor. Aspirin inhibits the release of Adenosine Diphosphate ( ADP ) from platelets. Also, it inhibits the synthesis of prostaglandins and thromboxane A2. All these mechanisms inhibit platelet aggregation. ADVERSE EFFECT :- GIT disturbance like nausea , vomiting , diarrhoea. Ulceration , perforation , hemorrhage. Intolerance. Fatty infilteration of liver , kidney.

18. 5. Salicylism. Bone marrow depression leading to agranulocytosis , thrombocytopenia , aplastic anaemia. pK: - Absorbed from liver , stomach , smallintestine. They are mainly concentrated in liver, heart, muscle and brain. They metabolised in liver by conjugation with glycine and glucoronic acid. DOSE :- 75 – 300 mg daily for antiplatelet action.

19. ASPIRIN

20. Dipyridamole :- It has no effect on the levels of thromboxane A2 or PG2. It acts by inhibiting Phosphodiesterase which in turn increase cyclic AMP. This inhibits platelets Aggregation. Dipyridamole is also a coronary Vasodialator. DOSE :- 100 mg two or three times a day.

21. Dipyridamole

22. Ticlopidine :- It is a new synthetic inhibitor of platelet aggregation. It has no effect on cyclooxygenase or Cyclic AMP . It inhibits platelet deposition, aggregation and release reaction. ADVERSE EFFECT :- Diarrhoea , Vomiting , Abdominal pain. Headache , tinnitis , skin rashes. Bleeding , Neutropenia , thrombocytopenia. DOSE :- 250 mg twice a day.

23. Ticlopidine

24. Clopidogrel :- It is a congenor of ticlopidine . It has similar mehanism as ticlopidine . It is better tolerated . It produces less neutropenia and thrombocytopenia than ticlopidine. ADVERSE EFFECT :; Diarrhoea , epigastris pain and rashes . Bleeding. DOSE :- 75 mg once daily

25. Clopidogrel

26. Thankyou