This document discusses fibrinolytics, which are agents that help dissolve blood clots through fibrinolysis. It describes the mechanisms of fibrinolysis and plasminogen activation. The main fibrinolytic agents discussed are streptokinase, urokinase, and tissue-type plasminogen activator. Their mechanisms of action and uses for conditions like myocardial infarction and pulmonary embolism are summarized. The document also discusses antiplatelet drugs, how they inhibit platelet aggregation, their classifications like aspirin and mechanisms of action. Adverse effects of various antiplatelet drugs are mentioned.
2. Fibrinolysis: - The process of dissolution of the Clot
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.
4. MECHANISM OF FIBRINOLYSIS: -
1. Plasminogen is the inactive precursor present in plasma.
2. It is converted to Plasmin by an Activator Substance present in blood
and tissues.
3. Plasmin can break down clots.
4. Plasminogen Plasmin Clot Dissolution.
1. All fibrinolytic agents currently in use act directly or indirectly as
plasminogen activators.
2. They produce lyses of an already formed clot.
3. So they are curative rather than prophylactic.
4. They can be injected ->
• 1)Intraarterially close to thombus for a localised effect.
• 2)Intravenously for a generalized effect in multiple Thrombi.
Clobdj
5. USES : - Fibrinolytic agents are used in :
1. Myocardial Infarction
2. Pulmonary embolism
3. Deep vein thrombosis
4. Peripheral arterial occlusion
5. Ischemic Stroke
FIBRINOLYTICS AGENTS ARE: -
1. Streptokinase
2. Urokinase
3. Tissue - Type Plasminogen Activator
6. STREPTOKINASE :-
• It is a fibrinolytic agent obtained from beta hemolytic
Streptococci.
• 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.
7. ADVERSE EFFECTS: -
• It is Antigenic and so produces hypersensitivity reactions.
• It produce local irritation and dangerous haemorrhage.
• It produce fever.
• Bleeding.
• Hypotension.
• Arrythmias.
9. UROKINASE: -
• It is an Enzyme prepared from human urine.
• It is now prepared from cultured human kidney cells.
• Unlike Streptokinase It is :-
1. Non – Antigenic
2. Non- Pyrogenic
3. Does not produce Alergic reactions.
4. Is is Expensive.
11. 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.
13. 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
14. • 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).
15. • Antiplatelet drugs inhibit platelet aggregation.
• So they are useful in the prevention and treatment of thrombosis in
conditions like
1. myocardial infarction
2) myocardial ischemia
3) cerebral ischemia.
• Prostacyclin (PGI2) synthesised in blood vessels is a natural inhibitor
of platelet aggregation.
18. 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 :-
1. GIT disturbance like nausea , vomiting , diarrhoea.
2. Ulceration , perforation , hemorrhage.
3. Intolerance.
4. Fatty infilteration of liver , kidney.
19. 5. Salicylism.
6. 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.
21. 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.
23. 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.
25. 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