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 catheter (CVC).[3] It is given by injection into a vein or artery.[3]

Blood flow obstructed by coagulated blood that could potentially be reversed with alteplase.

Medical uses

The main uses of alteplase are acute ischemic stroke, acute myocardial infarction, and acute massive pulmonary embolism.[1] The use of alteplase is similar to those of other thrombolytic drugs, but can vary depending on the pathology.[4][5]

Ischemic stroke

In people diagnosed with acute ischemic stroke, thrombolytic treatment with alteplase may be considered.[5] A person may benefit from treatment with alteplase if:[5][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
  • aged 18 years or older

Myocardial infarction

Currently, the preferred treatment for ST elevation myocardial infarction (STEMI) is percutaneous coronary intervention (PCI).[4] If a person is experiencing a STEMI, is being treated at 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

As of 2019, alteplase is the most commonly used medication to treat pulmonary embolism (PE).[7] Alteplase has a short infusion time of 2 hours and a half-life of 4-6 minutes.[7] Alteplase has been approved by the FDA, and treatment can be done via systemic thrombolysis or catheter-directed thrombolysis.[7][8]

Systemic thrombolysis can quickly restore right ventricular function, heart rate, and blood pressure in patients with acute PE.[9] However, standard doses of alteplase used in systemic thrombolysis may lead to massive bleeding, such as intracranial hemorrhage, particularly in older patients.[7] A systematic review has shown that that low-dose alteplase is safer than and as effective as the standard amount.[10]

Catheter-directed thrombolysis may be more efficient than systemic thrombolysis, as alteplase is locally administered to the occlusion site, and wash-away of the medication into other blood vessels is minimized.[9] This procedure involves positioning a multi-sidehole catheter into the blood clot.[9]

Alteplase may be used to treat PE if patients have a high risk for complications, such as if:[11]

Blocked catheters

Alteplase can be used in small doses to clear blood clots that obstruct a catheter, reopening the catheter so it can continue to be used.[14] Catheter obstruction is commonly observed with a central venous catheter.[15] Alteplase is effective and low risk for treating blocked catheters in adults.[15] For children, alteplase has been found to be safe and effective for clearing blocked catheters with no adverse effects.[15] Overall, adverse effects of alteplase for clearing blood clots are rare.[16]

Contraindications

A person should not receive alteplase treatment if testing shows they are not suffering from an acute ischemic stroke or if the risks of treatment outweigh the likely benefits.[5]

People with an acute ischemic stroke may also receive other therapies including mechanical thrombectomy.[5] Additional contraindications for alteplase when used specifically for acute ischemic stroke include current intracranial hemorhage and subarachnoid hemorrhage.[17] Contraindications for use of alteplase in people with a STEMI are similar to those of acute ischemic stroke.[4]

Adverse effects

Given that alteplase is a thrombolytic medication, a common adverse effect is bleeding, which can be life threatening.[18]

Angioedema is another adverse effect of alteplase, which can be life-threatening if the airway becomes obstructed.[1] Other side effects may rarely include allergic reactions.[3] Alteplase is a pregnancy category C drug.[2]

Mechanism of action

Depiction of the pathway that Alteplase (t-PA) uses to promote the degradation of a blood clot (fibrin).

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.[1]

Society and culture

Alteplase was added to the World Health Organization's List of Essential Medicines in 2019.[19][20]

History

Alteplase was approved for medical use in the United States in November 1987.[1][3][21]

References

  1. ^ a b c d e "Activase- alteplase kit". DailyMed. 5 December 2018. Retrieved 4 January 2020.
  2. ^ a b "Alteplase Use During Pregnancy". Drugs.com. Retrieved 12 November 2019.
  3. ^ a b c d "Alteplase Monograph for Professionals". Drugs.com. Retrieved 11 November 2019.
  4. ^ a b c d O'Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA, et al. (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): e362-425. doi:10.1161/CIR.0b013e3182742cf6. PMID 23247304.
  5. ^ a b c d e Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. (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. PMID 31662037.
  6. ^ Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, et al. (February 2016). "Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association". Stroke. 47 (2): 581–641. doi:10.1161/STR.0000000000000086. ISSN 1524-4628. PMID 26696642. S2CID 9381101.
  7. ^ a b c d Department of Pulmonary Diseases, Ataturk University School of Medicine, Erzurum, Turkey; Yilmazel Ucar, Elif (14 June 2019). "Update on Thrombolytic Therapy in Acute Pulmonary Thromboembolism". The Eurasian Journal of Medicine. 51 (2): 185–189. doi:10.5152/eurasianjmed.2019.19291. PMC 6592452. PMID 31258361.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Martin, Colleen; Sobolewski, Kristine; Bridgeman, Patrick; Boutsikaris, Daniel (December 2016). "Systemic Thrombolysis for Pulmonary Embolism: A Review". P & T: A Peer-Reviewed Journal for Formulary Management. 41 (12): 770–775. ISSN 1052-1372. PMC 5132419. PMID 27990080.
  9. ^ a b c Engelberger, R. P.; Kucher, N. (3 February 2014). "Ultrasound-assisted thrombolysis for acute pulmonary embolism: a systematic review". European Heart Journal. 35 (12): 758–764. doi:10.1093/eurheartj/ehu029. ISSN 0195-668X.
  10. ^ Zhang, Zhu; Zhai, Zhen-guo; Liang, Li-rong; Liu, Fang-fang; Yang, Yuan-hua; Wang, Chen (March 2014). "Lower dosage of recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute pulmonary embolism: A systematic review and meta-analysis". Thrombosis Research. 133 (3): 357–363. doi:10.1016/j.thromres.2013.12.026. ISSN 0049-3848.
  11. ^ Wan S, Quinlan DJ, Agnelli G, Eikelboom JW (August 2004). "Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: a meta-analysis of the randomized controlled trials". Circulation. 110 (6): 744–9. doi:10.1161/01.CIR.0000137826.09715.9C. PMID 15262836. S2CID 7663879.
  12. ^ a b "Management of PE". American College of Cardiology. Retrieved 30 October 2020.
  13. ^ a b Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. (February 2016). "Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report". Chest. 149 (2): 315–352. doi:10.1016/j.chest.2015.11.026. PMID 26867832.
  14. ^ Reed M, Kerndt CC, Nicolas D (2020). "Alteplase". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 29763152. Retrieved 30 October 2020.
  15. ^ a b c Baskin JL, Reiss U, Wilimas JA, Metzger ML, Ribeiro RC, Pui CH, Howard SC (May 2012). "Thrombolytic therapy for central venous catheter occlusion". Haematologica. 97 (5): 641–50. doi:10.3324/haematol.2011.050492. PMC 3342964. PMID 22180420.
  16. ^ Hilleman D, Campbell J (October 2011). "Efficacy, safety, and cost of thrombolytic agents for the management of dysfunctional hemodialysis catheters: a systematic review". Pharmacotherapy. 31 (10): 1031–40. doi:10.1592/phco.31.10.1031. PMID 21950645. S2CID 2092899.
  17. ^ Parker, Sarah; Ali, Yasmin (October 2015). "Changing Contraindications for t-PA in Acute Stroke: Review of 20 Years Since NINDS". Current Cardiology Reports. 17 (10): 81. doi:10.1007/s11886-015-0633-5. ISSN 1523-3782. PMID 26277361. S2CID 26427160.
  18. ^ Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, et al. (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): 1929–35. doi:10.1016/S0140-6736(14)60584-5. PMC 4441266. PMID 25106063.
  19. ^ 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.
  20. ^ 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.
  21. ^ "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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