ALTEPLASE(rt-PA)

 ALTEPLASE (rt-PA)

BRAND NAME:-ACTILYSE 50mg vial with 50ml solvent water.

ALTEPLASE (rt-PA) ( recombinant tissue plasminogen activator) produced by  recombinant DNA technology from human tissue culture,it is moderately specific for fibrin- bound plasminogen,so that circulating fibriogen is lowered only by ~50% . It is rapidly cleared by liver and inactivated by plasminogen activator inhibitor-1 (PSA-1). The plasma t½ is 4-8min . Because of the short t½, it needs to be given by slow i .v . Infusion and often requires heparin co-administration . It is nonantigenic,but nausea,mild hypotension and fever may occur. It is expensive.

MECHANISM OF ACTION:-

Alteplase is a recombinant tissue plasminogen activator (rt-PA) that converts plasminogen to plasmin in a fibrin-dependent process. In the absence of fibrin, alteplase converts a limited amount of plasminogen. However, in the presence of fibrin clots, alteplase binds to fibrin and cleaves the arginine-valine bond at positions 560 and 561 of plasminogen, converting it into its active form, plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus and promotes clot dissolution. Alteplase initiates local fibrinolysis with limited systemic proteolysis

USED:-Alteplase is mainly used to treat acute ischemic stroke, acute myocardial infarction, acute massive pulmonary embolism, and blocked catheters.Similar to other thrombolytic drugs, alteplase is used to dissolve clots to restore tissue perfusion, but this can vary depending on the pathology. Generally, alteplase is delivered intravenously into the body.To treat blocked catheters, alteplase is administered directly into the catheter.

Alteplase has also been used off-label for deep vein thrombosis, peripheral artery disease, pleural effusion in children, prosthetic valve thrombosis, frostbite, and peritonitis.

DOSE:- 

For MI:(accelerated regimen) 15 mg i.v. bolus injection followed by 50mg over 30min,then 35 mg over the next 1 hr. (Total 90min).

For pulmonary embolism: 100mg i.v. infused over 2hr.

For ischaemic embolism: 0.9 mg/ kg by i.v. infusion over 60 min, with 10% of the dose injected in the first minute.

SIDE EFFECTS/ADVERSE EFFECTS:-.common side effect is bleeding, which can be life threatening. Adverse effects of alteplase include symptomatic intracranial hemorrhage and fatal intracranial hemorrhage.

Angioedema is another adverse effect of alteplase, which can be life-threatening if the airway becomes obstructed. Other side effects may rarely include allergic reactions.Alteplase is a pregnancy category C drug.