Morning Report: 9/21/2012

Thanks Dr. Coquillon for today’s Morning Report!

Alteplase:

Mechanism of Action

Recombinant human tissue-type plasminogen activator (t-PA); produces local fibrinolysis

Promotes thrombolysis by converting plasminogen to plasmin which degrades fibrin and fibrinogen

Pharmacokinetics

Initial Half-Life: 5 minutes (free unbound form)

Terminal Half-life: 72 minutes

Onset: Coronary thrombolysis occurs in 30 min, reaches peak response at 60 min

Peak Plasma Time: 20-40 min

Metabolism: Rapidly cleared from circulation by liver

Excretion: Urine

Alteplase Dosing:

Acute MI:

<67 kg: 15 mg IVP bolus over 1-2 minutes, THEN 0.75 mg/kg IV infusion over 30 minutes (not to exceed 50 mg); THEN 0.5 mg/kg IV over next 60 minutes (not to exceed 35 mg)

≥67 kg (100 mg total dose infused over 1.5 hr) 15 mg IVP bolus over 1-2 minutes, THEN 50 mg IV infusion over next 30 minutes, and THEN remaining 35 mg over next 60 minutes

Pulmonary Embolism:

100 mg IV infused over 2 hours

Initiate/restart IV heparin therapy near end or immediately following alteplase infusion when PTT returns to <2 times normal

Acute Ischemic Stroke

Treatment should only be initiated within 3 hours (controversial) after onset of stroke symptoms, Exclude intracranial hemorrhage by cranial computerized tomography (CT) scan or other diagnostic imaging method sensitive for the presence of hemorrhage

0.9 mg/kg IV infused over 1 hour, administer 10% of total dose as initial bolus over 1 minute; not to exceed total dose of 90 mg

Side effects:

1) Bleeding

The most frequent adverse reaction

Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, Activase (alteplase) therapy should be discontinued immediately.

The incidence of hemorrhagic stroke was 0.7%, not all of which were fatal. The incidence of all strokes, as well as that for hemorrhagic stroke, increased with increasing age .

	TOTAL DOSE ≤ 100 MG
gastrointestinal	5%
genitourinary	4%
ecchymosis	1%
retroperitoneal	< 1%
epistaxis	< 1%
gingival	< 1%

Allergic Reactions

Allergic-type reactions, e.g., anaphylactoid reaction, laryngeal edema, orolingual angioedema, rash, and urticaria have been reported. A cause and effect relationship to Activase (alteplase) therapy has not been established.

Most cases resolved with prompt treatment; there have been rare fatalities as a result of upper airway hemorrhage from intubation trauma.