Antiplatelets and fibrinolytics are used to treat thrombosis. Aspirin is the main antiplatelet drug and works by inhibiting platelet aggregation. Other antiplatelets include clopidogrel, dipyridamole, and GPIIb/IIIa inhibitors. Fibrinolytics such as streptokinase, alteplase, and tenecteplase dissolve blood clots by activating the body's fibrinolytic system. Antiplatelets are used to prevent arterial thrombosis and reduce risks of heart attack and stroke. Fibrinolytics are primarily used for heart attacks to restore blood flow in acute myocardial infarction. Both antiplatelets and fibrinolytics have benefits but also risks like bleeding that require consideration
2. Thrombosis
• Arterial Thrombosis :
– Adherence of platelets to arterial walls -
White in color - Often associated with MI,
stroke and ischemia
• Venous Thrombosis :
– Develops in areas of stagnated blood flow
(deep vein thrombosis), Red in color-
Associated with Congestive Heart Failure,
Cancer, Surgery.
9. Vascular endothelial cells can
synthesize new PGI2 but
platelets cannot synthesize
new TXA2.
Thus action of aspirin on
platelet is permanent lasting for
the lifetime of platelet i.e. 7-10
days.
Balance between TXA2
(promoter of aggregation) &
PGI2 ( inhibitor of aggregation)
10. As higher doses of aspirin are
needed to inhibit COX in
vascular endothelium than in
platelets, antiplatelet effect can
be achieved at low doses ( 75-
150 mg per day orally)
Other NSAIDs are reversible
inhibitors.
11. Limitations of Aspirin
•Multiple pathways of platelet activation in
vivo
Thrombin, collagen, high shear stress
activate
platelets via non-cyclooxygenase pathways
Catecholamines can overcome antiplatelet
effect
Platelet adhesion and thrombus formation
not
blocked
Prothrombotic effect at higher doses
Inhibition of vascular prostacyclin
generation
Inhibition of tPA (at doses >300 mg)
13. Adverse effects
• At lower dose mainly GIT adv. Effect:
A)GI mucosa damage
B)High risk of bleeding
C)Suppression of GI protective
action of PGs
14. Phosphodiaster Inhibitors:
• Dipyridamol:
• It inhibits Phosphodiasterase &
blocks uptake of adenosine to
increase cAMP which potentiate PGI2
& interfere with aggregation
• Dipyridamol+Aspirin-used in TIA
16. Clopidogrel
• Pro Drug
• Slow onset of action
• Fewer side effects than
Ticlodipine
• Dose dependent action –
within 5 hrs of oral loading
dose 80% of platelet activity
inhibited.
• Duration of antiplatelet effect 7-
10 days.
17. Ticlodipine
• Pro Drug
• 8-11 days to show maximal effect.
• Nausea, vomiting, diarrhoea.
• Thrombocytopenia
• Neutropenia
• Thrombotic Thrombocytopenic
Purpura – rare.
• Due to distinct MOA combo with
aspirin has additive or synergistic
effect.
• Used for sec. prevention of stroke
19. Abciximab
• Human murine chimeric
monoclonal antibody Fab
fragment
• Binds with high affinity and
slow dissociation rate.
• Immediate and profound
inhibition of platelet activity
extending for 12-36 hrs after
termination of infusion.
• 0.25mg/kg bolus followed by
0.125μg/kgper min for 12hrs
20. Eptifibatide/ Tirofiban
• • Prevent binding of fibrinogen to
• the receptor complex
• • Used to treat unstable angina
• • Used for angioplastic coronary
• interventions.
• • ADRs
• - Haemorrage
• - Thrombocytopenia
22. Clinical uses of antiplatelet drugs
The main drug is aspirin. Other
drugs with distinct actions (e.g.
dipyridamole, clopidogrel) can have
additive effects, or be used in
patients who are intolerant of aspirin.
Uses of antiplatelet drugs relate
mainly to arterial thrombosis and
include uses in:
acute myocardial infarction
high risk of myocardial infarction, including
a history of myocardial infarction, angina
– unstable Angina (clopidogrel is added to
aspirin)
24. – following coronary artery angioplasty
(PCI) – abciximab(I.V), are used in some
patients in addition to aspirin)
– transient cerebral ischaemic attack
('ministrokes') or thrombotic stroke, to
prevent recurrence (dipyridamole can be
added to aspirin)
– atrial fibrillation, if oral anticoagulation is
contraindicated.
• epoprostenol [PGI2]; have
specialised clinical applications in
haemodialysis or haemofiltration in
cases in which heparin is
25. FIBRINOLYTICS
• These drugs dissolve the Thrombi in
blood vessel(mainly coronary artery)
by activating fibrinolytic system
27. Streptokinase :1st
GEN:
• Streptokinase is a protein
• synthesized by streptococci that
• combines with proactivator
• plasminogen. Caution in patients
• with previous history of fibrinolytic
• therapy due to formation of
• antibodies.
• • Streptokinase- loading dose of
• 250,000 units followed by
• 100,000 units/hr for 24-72 hrs.
• • It is antigenic & can cause
hypersensitivity rxn when used
28. Urokinase
• Urokinase is a human enzyme
synthesized by the kidney that
directly converts plasminogen to
plasmin.
• Plasminogen can be activated
endogenously by t-PA.
Preferentially activate plasminogen
bound to fibrin
Non-antigenic
Indicated in pts. With sensitivity to
strepokinase
29. FIBRINOLYTICS
• 2ND
GEN: ALTEPLASE (TPA)
– Cleaves plasminogen plasmin
fibrinolysis
– Specific activity in thrombus, less
systemic fibrinolysis
– Weight-based IV infusion over 60-90min
– Half-life<5 min
– Heparin commonly administered shortly
after
• 2ND
GEN: ALTEPLASE (TPA)
– Cleaves plasminogen plasmin
fibrinolysis
– Specific activity in thrombus, less
systemic fibrinolysis
– Weight-based IV infusion over 60-90min
– Half-life<5 min
– Heparin commonly administered shortly
after
DOSE- 60 mg i.v.
over the first hour followed by
40 mg at a rate of 20 mg/hr.
32. FIBRINOLYTICS
• 3RD
GEN: modifications of TPA
– RETEPLASE
• Half-life= 18 min
• Double bolus regimen
– TENECTEPLASE (TNK)
• Half life= 20 min
• Single-weight tiered bolus dosing over 5-10s
*bolus-doses fewer med errors
* No absol mortality benefit in AMI
33. FIBRINOLYTICS: Clinical uses
• The main use is in acute myocardial
infarction, with ST segment elevation
on the ECG within 12 hours of onset
(the earlier the better!)
• Other uses include:
– acute thrombotic stroke within 3 hours of
onset (tPA), in selected patients
– clearing thrombosed shunts and
cannulae
– acute arterial thromboembolism
– life-threatening deep vein thrombosis
and pulmonary embolism (streptokinase,
given promptly).
34. Adv. Effect : These agents do not
distinguish b/w pathological thrombi &
fibrin deposit at site of vascular injury
35. Books To Be Referred:
• Lippincott
• F.s.k Barar
• Rang & Dale
• Goodman & Gillman
• K D Tripathi
• H L Sharma
• R K Goyal
• Photographs from Medical books
• Internet
37. Good ideas are not adopted automatically.
They must be driven into practice with
courageous patience.
--Hyman Rickover
US Admiral(1900-1986)
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