thrombolytic agents

Acute thromboembolic disease in selected patients may be treated by the administration of agents that activate the conversion of plasminogen to plasmin, that hydrolyzes fibrin and, thus, dissolves clots.

Plasminogen
?thrombolytic drugs
plasmin (hydrolysis of fibrin)
Therapeutic use:
DVT and PE, but tendency to cause bleeding has blunted their use in treating acute peripheral arterial thrombosis or MI. For MI, intracoronary delivery of the drugs is the most reliable
For achieving recanalization. However, cardiac catheterization may not be possible in the 2- to 6-hour “therapeutic window,”.?
Thus, thrombolytic agents are usually administered intravenously.
Restoring catheter and shunt function, by lysing clots that causing the occlusions.
side effect:
Hemorrhage. thrombolytic agents do not distinguish between wanted and un wanted thrombus fibrin.


contraindicated in /pregnancy, and
in patients with healing wounds, a history of cerebrovascular accident,
Active peptic ulcer, head trauma, intracranial bleeding
. Alteplase (known as tissue plasminogen activator or tPA. It is obtained as a product of recombinant DNA technology.
Alteplase activates plasminogen that is bound to fibrin in a thrombus or a hemostatic plug.
Thus, alteplase is said to be “fibrin selective”
Uses : MI, massive PE, and acute ischemic
stroke.
Alteplase has a very short half-life (5 to 30 minutes), and therefore,10% of the total dose is injected intravenously as a bolus and the remaining drug is administered over 60 minutes
. Streptokinase
Streptokinase is an extracellular protein from culture of ?-hemolytic streptococci. It forms an active one-to-one complex with plasminogen. This enzymatically active complex converts plasminogen to plasmin In addition to the hydrolysis of fibrin plugs, the
complex also catalyzes the degradation of fibrinogen, With the advent of newer agents,
streptokinase is rarely used and is no longer available in many market
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drugs for bleeding
Fibrinolytic states can be controlled by the
administration of aminocaproic acid or tranexamic acid.
Tranexamic acid is 10 times more potent than aminocaproic acid.
mechanism inhibit plasminogen activation.
side effect intravascular thrombosis.
antagonizes the anticoagulant effects of heparin. This .protein is derived from fish
:Protamine sulfate
mechanism of action the positively charged protamine interacts with the negatively charged heparin, forming a stable complex without anticoagulant activity.
Adverse effects
hypersensitivity dyspnea, flushing, bradycardia, and hypotension when rapidly injected.
Vitamin K
mechansim of action :Vitamin K1 administration can stop bleeding problems due to warfarin by increasing the supply of active vitamin K1, thereby inhibiting the effect of warfarin.

Route of given Vitamin K1
oral, subcutaneous, or intravenous route. [Note: Intravenous vitamin K should be administered by slow IV infusion to minimize the risk of hypersensitivity For the treatment of
bleeding, the subcutaneous route of vitamin K1 is not preferred, as it is not as effective as oral or IV administration. The response to vitamin K1 is slow, requiring about 24-36 hours to reduce INR (time to synthesize new coagulation factors). Thus, if immediate hemostasis is required, fresh frozen plasma should be infused