t-PA


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Related to t-PA: urokinase, heparin

TPA

 (t-PA)
2. total parenteral alimentation (see parenteral nutrition); t-plasminogen activator.

alteplase

(al-te-plase) ,

Activase

(trade name),

Cathflo Activase

(trade name),

tissue plasminogen activator

(trade name),

t-PA

(trade name)

Classification

Therapeutic: thrombolytics
Pharmacologic: plasminogen activators
Pregnancy Category: C

Indications

Acute myocardial infarction (MI).Acute ischemic stroke.Pulmonary embolism (PE).Occluded central venous access devices.Deep venous thrombosis (DVT).Acute peripheral arterial thrombosis.

Action

Directly converts plasminogen to plasmin, which then degrades clot-bound fibrin.

Therapeutic effects

Lysis of thrombi in coronary arteries, with improvement of ventricular function, and reduced risk of heart failure or death.
Lysis of pulmonary emboli.
Lysis of thrombi causing ischemic stroke, reducing risk of neurologic sequelae.
Restoration of cannula or catheter function.

Pharmacokinetics

Absorption: Complete after IV administration. Intracoronary administration or administration into occluded catheters or cannulae has a more localized effect.
Distribution: Unknown.
Metabolism and Excretion: Rapidly metabolized by the liver.
Half-life: 35 min.

Time/action profile (fibrinolysis)

ROUTEONSETPEAKDURATION
IV30 mi60 minunknown

Contraindications/Precautions

Contraindicated in: Active internal bleeding; History of cerebrovascular accident (for MI and PE only); Recent (within 3 mo) intracranial or intraspinal injury or trauma; Intracranial neoplasm, arteriovenous malformation, or aneurysm; Known bleeding diathesis; Severe uncontrolled hypertension (systolic BP >185 mmHg or diastolic BP >110 mmHg specifically for stroke indication); Evidence or suspicion of intracranial hemorrhage on pretreatment evaluation (for stroke indication only); Recent (within 3 mo) stroke (for stroke indication only); History of intracranial hemorrhage (for stroke indication only); Seizure at the onset of stroke (for stroke indication only); Current use of oral anticoagulants or an INR >1.7 or a prothrombin time >15 sec (for stroke indication only); Administration of heparin 48 hr before the onset of stroke with an elevated aPTT at presentation (for stroke indication only); Platelet count <100,000/mm3 (for stroke indication only); Hypersensitivity (for central venous access device occlusion indication only).
Use Cautiously in: Recent (within 10 days) major surgery, trauma, GI or GU bleeding; Cerebrovascular disease; Systolic BP ≥175 mmHg and/or diastolic BP ≥110 mmHg; High likelihood of left heart thrombus; Hemostatic defects; Severe hepatic impairment; Hemorrhagic ophthalmic conditions; Septic thrombophlebitis; Previous puncture of a noncompressible vessel; Subacute bacterial endocarditis or acute pericarditis; Severe neurological deficit (NIHSS >22) at presentation (for stroke indication only); Major early infarct signs on CT scan (for stroke indication only); Known or suspected infection in catheter (for central venous access device occlusion indication only); Geriatric: >75 yr; ↑ risk of intracranial bleeding; Obstetric / Lactation / Pediatric: Safety not established.
Exercise Extreme Caution in: Patients receiving concurrent anticoagulant therapy (↑ risk of intracranial bleeding).

Adverse Reactions/Side Effects

Central nervous system

  • intracranial hemorrhage (life-threatening)

Ear, Eye, Nose, Throat

  • epistaxis
  • gingival bleeding

Respiratory

  • bronchospasm
  • hemoptysis

Cardiovascular

  • reperfusion arrhythmias
  • hypotension
  • recurrent ischemia/thromboembolism (life-threatening)

Gastrointestinal

  • GI bleeding (life-threatening)
  • nausea
  • retroperitoneal bleeding (life-threatening)
  • vomiting

Genitourinary

  • GU tract bleeding (life-threatening)

Dermatologic

  • ecchymoses
  • flushing
  • urticaria

Hematologic

  • bleeding (life-threatening)

Local

  • hemorrhage at injection site
  • phlebitis at injection site

Musculoskeletal

  • musculoskeletal pain

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • fever

Interactions

Drug-Drug interaction

Aspirin, other NSAIDs, warfarin, heparin and heparin-like agents, abciximab, eptifibatide, tirofiban, clopidogrel, ticlopidine, or dipyridamole —concurrent use ↑ risk of bleeding, although these agents are frequently used together or in sequence.Effects may be ↓ by antifibrinolytic agents, including aminocaproic acid or tranexamic acid.↑ anticoagulant effect and bleeding risk with anise, arnica, chamomile, clove, dong quai, fenugreek, feverfew, garlic, ginger, ginkgo, Panax ginseng, licorice, and others.

Route/Dosage

Myocardial Infarction (Accelerated or Front-Loaded Regimen)

Intravenous (Adults) 15 mg bolus, then 0.75 mg/kg (up to 50 mg) over 30 min, then 0.5 mg/kg (up to 35 mg) over next 60 min; usually accompanied by heparin therapy.

Myocardial Infarction (Standard Regimen)

Intravenous (Adults >65 kg) 60 mg over 1st hr (6–10 mg given as a bolus over first 1–2 min), 20 mg over the 2nd hr, and 20 mg over the 3rd hr for a total dose of 100 mg.
Intravenous (Adults <65 kg) 0.75 mg/kg over 1st hr (0.075–0.125 mg/kg given as a bolus over first 1–2 min), 0.25 mg/kg over the 2nd hr, and 0.25 mg/kg over the 3rd hr for a total dose of 1.25 mg/kg (not to exceed 100 mg total).

Acute Ischemic Stroke

Intravenous (Adults) 0.9 mg/kg (not to exceed 90 mg), given as an infusion over 1 hr, with 10% of the dose given as a bolus over the 1st min.

Pulmonary Embolism

Intravenous (Adults) 100 mg over 2 hr; follow with heparin.

Occluded Venous Access Devices

Intravenous (Adults and Children >30 kg) 2 mg/2 mL instilled into occluded catheter; if unsuccessful, may repeat once after 2 hr.
Intravenous (Adults and Children <30 kg) 110% of the lumen volume (not to exceed 2 mg in 2 mL) instilled into occluded catheter; if unsuccessful, may repeat once after 2 hr.

Availability

Powder for injection: 2 mg/vial, 50 mg/vial, 100 mg/vial

Nursing implications

Nursing assessment

  • Begin therapy as soon as possible after the onset of symptoms.
    • Monitor vital signs, including temperature, continuously for myocardial infarction and at least every 4 hr during therapy for other indications. Do not use lower extremities to monitor BP. Notify health care professional if systolic BP >180 mm Hg or diastolic BP >110 mm Hg. Thrombolytic therapy should not be given if hypertension is uncontrolled. Inform health care professional if hypotension occurs. Hypotension may result from the drug, hemorrhage, or cardiogenic shock.
    • Assess patient carefully for bleeding every 15 min during the 1st hr of therapy, every 15–30 min during the next 8 hr, and at least every 4 hr for the duration of therapy. Frank bleeding may occur from sites of invasive procedures or from body orifices. Internal bleeding may also occur (decreased neurologic status; abdominal pain with coffee-grounds emesis or black, tarry stools; hematuria; joint pain). If uncontrolled bleeding occurs, stop medication and notify health care professional immediately.
    • Assess patient for hypersensitivity reaction (rash, dyspnea, fever, changes in facial color, swelling around the eyes, wheezing). If these occur, inform health care professional promptly. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
    • Assess neurologic status throughout therapy. Altered sensorium or neurologic changes may be indicative of intracranial bleeding.
  • Myocardial Infarction: Monitor ECG continuously. Notify health care professional if significant arrhythmias occur. IV lidocaine or procainamide (Pronestyl) may be ordered prophylactically. Monitor cardiac enzymes. Radionuclide myocardial scanning and/or coronary angiography may be ordered 7–10 days after therapy to monitor effectiveness of therapy.
    • Assess intensity, character, location, and radiation of chest pain. Note presence of associated symptoms (nausea, vomiting, diaphoresis). Administer analgesics as directed. Notify health care professional if chest pain is unrelieved or recurs.
    • Monitor heart sounds and breath sounds frequently. Inform health care professional if signs of HF occur (rales/crackles, dyspnea, S3 heart sound, jugular venous distention, relieved CVP).
  • Acute Ischemic Stroke: Assess neurologic status. Determine time of onset of stroke symptoms. Alteplase must be administered within 3–4.5 hr of onset (within 3 hrs in patients older than 80 years, those taking oral anticoagulants, those with a baseline National Institutes of Health Stroke Scale score 25, or those with both a history of stroke and diabetes).
  • Pulmonary Embolism: Monitor pulse, BP, hemodynamics, and respiratory status (rate, degree of dyspnea, ABGs).
  • Deep Vein Thrombosis/Acute Arterial Occlusion: Observe extremities and palpate pulses of affected extremities every hour. Notify health care professional immediately if circulatory impairment occurs. Computerized tomography, impedance plethysmography, quantitative Doppler effect determination, and/or angiography or venography may be used to determine restoration of blood flow and duration of therapy; however, repeated venograms are not recommended.
  • Cannula/Catheter Occlusion: Monitor ability to aspirate blood as indicator of patency. Ensure that patient exhales and holds breath when connecting and disconnecting IV syringe to prevent air embolism.
  • Lab Test Considerations: Hematocrit, hemoglobin, platelet count, fibrin/fibrin degradation product (FDP/fdp) titer, fibrinogen concentration, prothrombin time, thrombin time, and activated partial thromboplastin time may be evaluated before and frequently during therapy. Bleeding time may be assessed before therapy if patient has received platelet aggregation inhibitors.
    • Obtain type and crossmatch and have blood available at all times in case of hemorrhage.
    • Stools should be tested for occult blood loss and urine for hematuria periodically during therapy.
  • high alert: If local bleeding occurs, apply pressure to site. If severe or internal bleeding occurs, discontinue infusion. Clotting factors and/or blood volume may be restored through infusions of whole blood, packed RBCs, fresh frozen plasma, or cryoprecipitate. Do not administer dextran; it has antiplatelet activity. Aminocaproic acid (Amicar) may be used as an antidote.

Potential Nursing Diagnoses

Ineffective tissue perfusion (Indications)
Risk for injury (Side Effects)

Implementation

  • high alert: Overdose and under-dosage of thrombolytic medications have resulted in patient harm or death. Have second practitioner independently check original order, dose calculations, and infusion pump settings. Clarify orders that contain any of these abbreviations.
  • Do not confuse the abbreviation t-PA for alteplase (Activase) with the abbreviations TNK t-PA for tenecteplase (TNKase) and r-PA for reteplase (Retevase). Do not confuse Activase with Cathflo Activase or TNKase.
  • Thrombolytic agents should be used only in settings in which hematologic function and clinical response can be adequately monitored.
    • Starting two IV lines before therapy is recommended: one for the thrombolytic agent, the other for any additional infusions.
    • Avoid invasive procedures, such as IM injections or arterial punctures, with this therapy. If such procedures must be performed, apply pressure to all arterial and venous puncture sites for at least 30 min. Avoid venipunctures at noncompressible sites (jugular vein, subclavian site).
    • Acetaminophen may be ordered to control fever.
  • Intravenous Administration
  • pH: 7.3.
  • Intermittent Infusion: Vials are packaged with sterile water for injection (without preservatives) to be used as diluent. Do not use bacteriostatic water for injection. Reconstitute 50-mg vials with 50 mL and 100–mg with 100 mL using an 18-gauge needle. Avoid excess agitation during dilution; swirl or invert gently to mix. Solution may foam upon reconstitution. Bubbles will resolve upon standing a few min. Solution will be clear to pale yellow. Stable for 8 hr at room temperature. Concentration: May be administered as reconstituted (1 mg/mL). Diluent: May be further diluted immediately before use in an equal amount of 0.9% NaCl or D5W.
  • Rate: Flush line with 20–30 mL of saline at completion of infusion to ensure entire dose is received. See Route and Dosage section for specific rates.
  • Y-Site Compatibility: eptifibatide, lidocaine, metoprolol, propranolol
  • Y-Site Incompatibility: bivalrudin, dobutamine, dopamine, heparin, nitroglycerin
  • Cathflo Activase: Reconstitute by withdrawing 2.2 mL of sterile water (provided) and injecting into Cathflo Activase vial, directing diluent into powder for a concentration of 1 mg/mL. Allow slight foaming to dissipate by letting vial stand undisturbed. Do not use bacteriostatic water. Mix by gently swirling to dissolve; complete dissolution should occur within 3 min. Do not shake. Solution should be colorless to pale yellow. Use solution within 8 hr.
    • Withdraw 2.0 mL of reconstituted solution and instill into occluded catheter. After 30 min dwell time, attempt to aspirate blood. If catheter remains occluded, allow 120 min dwell time. If catheter function is not restored after one dose, second dose may be instilled. If catheter function is restored, aspirate 4–5 mL of blood in patients ≥10 kg or 3 mL in patients <10 kg to remove Cathflo Activase and residual clot. Gently irrigate catheter with 0.9% NaCl.

Patient/Family Teaching

  • Explain purpose of medication and the need for close monitoring to patient and family. Instruct patient to report hypersensitivity reactions (rash, dyspnea) and bleeding or bruising.
  • Explain need for bedrest and minimal handling during therapy to avoid injury. Avoid all unnecessary procedures such as shaving and vigorous tooth brushing.

Evaluation/Desired Outcomes

  • Lysis of thrombi and restoration of blood flow.
  • Prevention of neurologic sequelae in acute ischemic stroke.
  • Cannula or catheter patency.

t-PA

Activase®, Alteplase®, tissue-plasminogen activator Cardiology A thrombolytic that upregulates fibrinolysis, activating conversion of plasminogen to plasmin, an enzyme that degrades fibrin clots, fibrinogen, and other clotting factors, ergo reperfusing Pts with acutely occluded coronary arteries; SK has a half-life of 6-8 minutes, an expected 60-80% rate of reperfusion, is nonallergenic and nonantigenic, evokes little hypotension, and is theoretically, more clot specific. See Thrombolytic therapy. Cf APSAC, Streptokinase.

t-PA

tissue plasminogen activator.
References in periodicals archive ?
Food and Drug Administration is a treatment option for patients who do not meet the criteria for t-PA (Jauch et al.
Insight into the regulation of t-PA synthesis may be helpful in developing drugs that counteract insufficient endogenous t-PA by increasing its production.
While the NINDS study (2) established that IV t-PA was useful if given to patients with nonhemorrhagic stroke within 3 hours of symptom onset regardless of associated parenchymal ischemic changes, the European Cooperative Acute Stroke Study (ECASS) trial (10) studied patients with stroke symptoms of <6 hours' duration who had CT-demonstrable ischemic changes involving no more than one third of the MCA territory.
About 50 percent of stroke patients treated with t-PA recover fully, but patients who suffer severe strokes have only an 8 percent chance of significant improvement on t-PA, according to an article on the Web site eMedicine.
Q: It seems that the problem in many emergency rooms is that the time between diagnosing the stroke and administering the t-PA often extends beyond the critical window of opportunity.
t-PA is released from the endothelium and facilitates the digestion of on-site fibrin clots.
The study involved 624 patients treated within three hours of onset of acute ischemic stroke and compared the results of using the drug t-PA (tissue plasminogen activator) or a look-alike placebo.
physicians choose t-PA over streptokinase, which is a tenth the cost and arguably as good.
Marler notes that the researchers also confirmed suspicions that t-PA increases a person's risk of having a serious brain hemorrhage.
By studying 631 male physicians randomly selected from a larger health study, the researchers found an association between moderate alcohol consumption and the body's production of t-PA antigen, which plays a central role in preventing thrombosis, or chronic internal blood clotting.
When doctors administer the clot-dissolving drugs streptokinase or t-PA, they can count on them restoring blood flow promptly in about 50 or 75% of patients, respectively.
The key element in such genetic modifications is the gene for the anti-clotting substance t-PA (tissue plasminogen activator) specially configured so that it would be secreted at levels potentially high enough to prevent clot formation inside a blood vessel graft.