Alteplase

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Alteplase
Clinical data
Trade namesActivase, Actilyse, others
Other namest-PA, rt-PA
AHFS/Drugs.comMonograph
License data
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC2569H3928N746O781S40
Molar mass59042.52 g·mol−1
  (verify)

Alteplase (t-PA) is a thrombolytic medication, used to treat acute ST elevation myocardial infarction (a type of heart attack), pulmonary embolism associated with low blood pressure, acute ischemic stroke, and blocked central venous access devices (CVAD).[2] It is given by injection into a vein or artery.[2]

Blood flow obstructed by coagulated blood that may possibly be reversed with alteplase.

Medical uses

The main uses of alteplase are acute ischemic stroke, acute myocardial infarction, and acute massive pulmonary embolism.[3]

The use of alteplase is similar to those of other thrombolytics, but can vary depending on the pathology.[4][5]

Ischemic stroke

After a patient is diagnosed with an acute ischemic stroke, they may be eligible for treatment with alteplase.[6] A person may be eligible for treatment with alteplase if:[6]

  • they are being treated within 4.5 hours of symptom onset
  • do not have other causes of stroke symptoms
  • benefits of treatment are determined to outweigh the risks

Myocardial infarction

Currently, the preferred treatment for ST elevation myocardial infarction (STEMI) is percutaneous coronary intervention (PCI).[4] If a person suffering from a STEMI is treated in a non-PCI capable hospital and cannot be transferred to receive PCI in under 120 minutes, they may be eligible for treatment with alteplase in combination with other drugs.[4]

Pulmonary embolism

Alteplase may be used in the treatment of pulmonary embolism if the patient is high risk.[7] A person with a pulmonary embolism may be high risk if:

Blocked catheters

Contraindications

A patient would not eligible for alteplase if testing shows they are not suffering from an acute ischemic stroke or if the risks of treatment outweigh the likely benefits.[6] Some considerations include:[6]

  • Computed tomography shows irreversible brain damage
  • Mild, nondisabling stroke symptoms
  • Blood pressure greater than 185/110 mm Hg
  • Blood glucose less than 50 mg/dL
  • Recent history of severe head trauma
  • History of or current intracranial hemorrhage
  • Infective endocarditis
  • Aortic arch dissection
  • Bleeding disorder (coagulopathy)
  • Other risk factors for severe bleeding such as recent surgeries, GI bleeding, GI cancer, and others

People suffering from an acute ischemic stroke may also be treated with other therapies including mechanical thrombectomy.[6]

Contraindications for use of alteplase in STEMI are similar to those of acute ischemic stroke.[4] A person suffering from a STEMI may be eligible to receive alteplase if the risks of treatment outweigh the likely benefits.[4]

Adverse Effects

Because alteplase is a thrombolytic medication, its main and potentially life-threatening adverse effect is bleeding.[11]

Common side effects are bleeding including intracranial bleeding and GI bleeding.[2] Other side effects may rarely include allergic reactions.[2] It is not recommended in those allergic to gentamicin.[12] Safety of use in pregnancy is unclear.[1]

Mechanism of action

Alteplase is a serine protease that assists fibrin in the conversion of plasminogen to plasmin. When in the systemic circulation, alteplase binds to fibrin in a thrombus and initiates fibrinolysis.[3]

Society and culture

Alteplase was added to the World Health Organization's List of Essential Medicines[13] in 2019.[14]

History

Alteplase was approved for medical use in the United States in 1987.[2][15]

References

  1. ^ a b "Alteplase Use During Pregnancy". Drugs.com. Retrieved 12 November 2019.
  2. ^ a b c d e "Alteplase Monograph for Professionals". Drugs.com. Retrieved 11 November 2019.
  3. ^ a b "Activase- alteplase kit". DailyMed. 5 December 2018. Retrieved 4 January 2020.
  4. ^ a b c d e WRITING COMMITTEE MEMBERS*; O’Gara, Patrick T.; Kushner, Frederick G.; Ascheim, Deborah D.; Casey, Donald E.; Chung, Mina K.; de Lemos, James A.; Ettinger, Steven M.; Fang, James C.; Fesmire, Francis M.; Franklin, Barry A. (29 January 2013). "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Circulation. 127 (4). doi:10.1161/CIR.0b013e3182742cf6. ISSN 0009-7322.
  5. ^ Powers, William J.; Rabinstein, Alejandro A.; Ackerson, Teri; Adeoye, Opeolu M.; Bambakidis, Nicholas C.; Becker, Kyra; Biller, José; Brown, Michael; Demaerschalk, Bart M.; Hoh, Brian; Jauch, Edward C. (December 2019). "Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association". Stroke. 50 (12). doi:10.1161/STR.0000000000000211. ISSN 0039-2499.
  6. ^ a b c d e Powers, William J.; Rabinstein, Alejandro A.; Ackerson, Teri; Adeoye, Opeolu M.; Bambakidis, Nicholas C.; Becker, Kyra; Biller, José; Brown, Michael; Demaerschalk, Bart M.; Hoh, Brian; Jauch, Edward C. (December 2019). "Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association". Stroke. 50 (12): e344–e418. doi:10.1161/STR.0000000000000211. ISSN 1524-4628. PMID 31662037.
  7. ^ Wan, Susan; Quinlan, Daniel J.; Agnelli, Giancarlo; Eikelboom, John W. (10 August 2004). "Thrombolysis Compared With Heparin for the Initial Treatment of Pulmonary Embolism: A Meta-Analysis of the Randomized Controlled Trials". Circulation. 110 (6): 744–749. doi:10.1161/01.CIR.0000137826.09715.9C. ISSN 0009-7322.
  8. ^ "Management of PE". American College of Cardiology. Retrieved 30 October 2020. {{cite web}}: Check |url= value (help)
  9. ^ a b Kearon, Clive; Akl, Elie A.; Ornelas, Joseph; Blaivas, Allen; Jimenez, David; Bounameaux, Henri; Huisman, Menno; King, Christopher S.; Morris, Timothy A.; Sood, Namita; Stevens, Scott M. (2016-02). "Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report". Chest. 149 (2): 315–352. doi:10.1016/j.chest.2015.11.026. ISSN 1931-3543. PMID 26867832. {{cite journal}}: Check date values in: |date= (help)
  10. ^ "Management of PE". American College of Cardiology. Retrieved 30 October 2020. {{cite web}}: Check |url= value (help)
  11. ^ Emberson, Jonathan; Lees, Kennedy R.; Lyden, Patrick; Blackwell, Lisa; Albers, Gregory; Bluhmki, Erich; Brott, Thomas; Cohen, Geoff; Davis, Stephen; Donnan, Geoffrey; Grotta, James (29 November 2014). "Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials". Lancet. 384 (9958): 1929–1935. doi:10.1016/S0140-6736(14)60584-5. ISSN 1474-547X. PMC 4441266. PMID 25106063.
  12. ^ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 216. ISBN 9780857113382.
  13. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  14. ^ World Health Organization (2019). Executive summary: the selection and use of essential medicines 2019: report of the 22nd WHO Expert Committee on the selection and use of essential medicines. Geneva: World Health Organization. hdl:10665/325773. WHO/MVP/EMP/IAU/2019.05. License: CC BY-NC-SA 3.0 IGO.
  15. ^ "Activase: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 4 January 2020.

External links

  • "Alteplase". Drug Information Portal. U.S. National Library of Medicine.
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