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2021, Número S1

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Rev Cubana Invest Bioméd 2021; 40 (S1)


Acciones cardiovasculares directas del paracetamol

Galán ML, Fontes OEA

Idioma: Español
Referencias bibliográficas: 48
Paginas:
Archivo PDF: 512.14 Kb.


RESUMEN

Introducción: El paracetamol es uno de los antiinflamatorios no esteroideos con efecto analgésico y antipirético más utilizados a nivel mundial. Pocos estudios se enfocan en esclarecer los mecanismos de acción a nivel cardiovascular.
Objetivos: Evaluar la acción del paracetamol sobre la fuerza de contracción de anillos de aorta torácica y sobre la actividad eléctrica y contráctil de corazones aislados y perfundidos de ratas Wistar.
Métodos: Se midieron los efectos del paracetamol sobre anillos de aorta de rata denudados de su endotelio vascular. Se estudiaron las acciones del fármaco sobre los corazones aislados y perfundidos de las ratas por el método de Langendorff. Se evaluó la amplitud de la fuerza de contracción cardiaca y los intervalos QT, QTc, QRS y RR del electrocardiograma. Las condiciones (control y presencia de paracetamol) fueron comparadas con una prueba t de Student para muestras pareadas (p < 0,05), previa comprobación de la normalidad de los datos.
Resultados: El paracetamol no tuvo efectos sobre el músculo liso vascular de los anillos aórticos ni sobre los intervalos QT, QTc, QRS y RR del electrocardiograma bajo ninguna de las concentraciones empleadas. Por otra parte, mostró efecto inotrópico negativo estadísticamente significativo en los corazones aislados, de forma dependiente de la concentración del fármaco. La IC50 estimada para la inhibición de la fuerza de contracción cardiaca fue de 17,15 ± 5,33 µmol/L.
Conclusiones: Las acciones cardiovasculares directas del paracetamol son modestas, lo cual contribuye al buen margen de seguridad para su uso en clínica, en pacientes sin enfermedad cardiovascular.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Chiam E, Weinberg L, Bellomo R. Paracetamol: a review with specific focus on the haemodynamic effects of intravenous administration. Heart, lung and vessels. 2015;7(2):121.

  2. Brune K, Renner B, Tiegs G. Acetaminophen/paracetamol: a history of errors, failures and false decisions. Eur J Pain. 2015;19(7):953-65.

  3. McCrae JC, Morrison EE, MacIntyre IM, Dear JW, Webb DJ. (2018). Long-term adverse effects of paracetamol - a review. Br J Clin Pharmacol. 2018;84(10):2218-30. DOI: https://doi.org/10.1111/bcp.13656

  4. Przybyla GW, Szychowski KA, Gminski J. Paracetamol - An old drug with new mechanisms of action. Clin Exp Pharmacol Physiol. 2020 Aug 7;00:1-17. DOI: https://doi.org/10.1111/1440-1681.13392

  5. Khabazianzadeh F, Kazemi T, Nakhaee S, Ng PC, Mehrpour O. Acetaminophen poisoning-induced heart injury: a case-based review. DARU J Pharm Sci. 2019:1-13.

  6. Kaya H, Polat B, Albayrak A, Mercantepe T, Buyuk B. Protective effect of an L-type calcium channel blocker, amlodipine, on paracetamol-induced hepatotoxicity in rats. Hum Exp Toxicol. 2018;37(11):1169-79.

  7. Smith AJ. Guidelines for planning and conducting high-quality research and testing on animals. Lab Anim Res. 2020 [acceso 24/10/2020];36:21. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348107/7.

  8. Galán-Martínez L, Herrera-Estrada I, Fleites-Vázquez A. Direct actions of the flavonoids naringenin, quercetin and genistein on rat cardiac and vascular muscles. J Pharm Pharmacogn Res. 2018;6(3):158-66.

  9. Keeble J, Al-Swayeh O, Moore P. Vasorelaxant effect of nitric oxide releasing steroidal and nonsteroidal anti-inflammatory drugs. Br J Pharmacol. 2001;133(7):1023-8.

  10. Van Der Horst J, Manville RW, Hayes K, Thomsen MB, Abbott GW, Jepps TA. Acetaminophen (Paracetamol) Metabolites Induce Vasodilation and Hypotension by Activating Kv7 Potassium Channels Directly and Indirectly. Arterioscler Thromb Vasc Biol. 2020;40(5):1207-19.

  11. Chiam E, Bellomo R, Churilov L, Weinberg L. The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study. PLoS One. 2018;13(4).

  12. Achuff BJ, Moffett BS, Acosta S, Lasa JJ, Checchia PA, Rusin CG. Hypotensive response to IV acetaminophen in pediatric cardiac patients. Pediatr Crit Care Med. 2019;20(6):527-33.

  13. Nahum E, Weissbach A, Kaplan E, Kadmon G. Hemodynamic effects of intravenous paracetamol in critically ill children with septic shock on inotropic support. J Intensive Care. 2020;8:14. DOI: https://doi.org/10.1186/s40560-020-0430-0

  14. Kelly S, Moran J, Williams P, Burns K, Rowland A, Miners J, et al. Haemodynamic effects of parenteral vs. enteral paracetamol in critically ill patients: a randomised controlled trial. Anaesthesia. 2016;71(10):1153-62.

  15. Maxwell EN, Jonson B, Cammilleri J, Ferreira JA. Intravenous Acetaminophen-Induced Hypotension: A Review of the Current Literature. Ann Pharmacother. 2019 Oct; 53(10):1033-41. DOI: https://doi.org/10.1177/1060028019849716

  16. Merrill GF. Acetaminophen and low-flow myocardial ischemia: efficacy and antioxidant mechanisms. J Physiol Heart Circ Physiol. 2002;282(4):H1341-H1349.

  17. Merrill GF, Rork TH, Spiler NM, Golfetti R. Acetaminophen and myocardial infarction in dogs. J Physiol Heart Circ Physiol. 2004;287(5):H1913-H1920.

  18. Merrill GF, Merrill JH, Golfetti R, Jaques KM, Hadzimichalis NS, Baliga SS, et al. Antiarrhythmic properties of acetaminophen in the dog. Exp Biol Med. 2007;232(9):1245-52.

  19. Doyon S, Klein-Schwartz W, Lee S, Beuhler MC. Fatalities involving acetaminophen combination products reported to United States poison centers. Clin Toxicol. 2013;51(10):941-8.

  20. García-Fuertes D, Villanueva-Fernández E, Crespín-Crespín M. 2016. Drug-induced long-QT and torsades de pointes in elderly polymedicated patients. Arq Bras Cardiol. 2016;106(2):156-9.

  21. Merrill GF, Mcconnell P, Vandyke K, Powell S. Coronary and myocardial effects of acetaminophen: protection during ischemia-reperfusion. J Physiol Heart Circ Physio. 2001;280(6):H2631-H2638.

  22. Forrest JA, Clements J, Prescott L. Clinical pharmacokinetics of paracetamol. Clin Pharmacokinet. 1982;7(2):93-107.

  23. Hall JE. Guyton y Hall. Tratado de fisiología médica. Barcelona, España: Elsevier; 2016: p. 3948.

  24. Godfraind T. Discovery and Development of Calcium Channel Blockers. Front Pharmacol. 2017;8:286. DOI: https://doi.org/10.3389/fphar.2017.00286

  25. Chiam E, Weinberg L, Bellomo R. Paracetamol: a review with specific focus on the haemodynamic effects of intravenous administration. Heart, lung and vessels. 2015;7(2):121.

  26. Brune K, Renner B, Tiegs G. Acetaminophen/paracetamol: a history of errors, failures and false decisions. Eur J Pain. 2015;19(7):953-65.

  27. McCrae JC, Morrison EE, MacIntyre IM, Dear JW, Webb DJ. (2018). Long-term adverse effects of paracetamol - a review. Br J Clin Pharmacol. 2018;84(10):2218-30. DOI: https://doi.org/10.1111/bcp.13656

  28. Przybyla GW, Szychowski KA, Gminski J. Paracetamol - An old drug with new mechanisms of action. Clin Exp Pharmacol Physiol. 2020 Aug 7;00:1-17. DOI: https://doi.org/10.1111/1440-1681.13392

  29. Khabazianzadeh F, Kazemi T, Nakhaee S, Ng PC, Mehrpour O. Acetaminophen poisoning-induced heart injury: a case-based review. DARU J Pharm Sci. 2019:1-13.

  30. Kaya H, Polat B, Albayrak A, Mercantepe T, Buyuk B. Protective effect of an L-type calcium channel blocker, amlodipine, on paracetamol-induced hepatotoxicity in rats. Hum Exp Toxicol. 2018;37(11):1169-79.

  31. Smith AJ. Guidelines for planning and conducting high-quality research and testing on animals. Lab Anim Res. 2020 [acceso 24/10/2020];36:21. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348107/7.

  32. Galán-Martínez L, Herrera-Estrada I, Fleites-Vázquez A. Direct actions of the flavonoids naringenin, quercetin and genistein on rat cardiac and vascular muscles. J Pharm Pharmacogn Res. 2018;6(3):158-66.

  33. Keeble J, Al-Swayeh O, Moore P. Vasorelaxant effect of nitric oxide releasing steroidal and nonsteroidal anti-inflammatory drugs. Br J Pharmacol. 2001;133(7):1023-8.

  34. Van Der Horst J, Manville RW, Hayes K, Thomsen MB, Abbott GW, Jepps TA. Acetaminophen (Paracetamol) Metabolites Induce Vasodilation and Hypotension by Activating Kv7 Potassium Channels Directly and Indirectly. Arterioscler Thromb Vasc Biol. 2020;40(5):1207-19.

  35. Chiam E, Bellomo R, Churilov L, Weinberg L. The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study. PLoS One. 2018;13(4).

  36. Achuff BJ, Moffett BS, Acosta S, Lasa JJ, Checchia PA, Rusin CG. Hypotensive response to IV acetaminophen in pediatric cardiac patients. Pediatr Crit Care Med. 2019;20(6):527-33.

  37. Nahum E, Weissbach A, Kaplan E, Kadmon G. Hemodynamic effects of intravenous paracetamol in critically ill children with septic shock on inotropic support. J Intensive Care. 2020;8:14. DOI: https://doi.org/10.1186/s40560-020-0430-0

  38. Kelly S, Moran J, Williams P, Burns K, Rowland A, Miners J, et al. Haemodynamic effects of parenteral vs. enteral paracetamol in critically ill patients: a randomised controlled trial. Anaesthesia. 2016;71(10):1153-62.

  39. Maxwell EN, Jonson B, Cammilleri J, Ferreira JA. Intravenous Acetaminophen-Induced Hypotension: A Review of the Current Literature. Ann Pharmacother. 2019 Oct; 53(10):1033-41. DOI: https://doi.org/10.1177/1060028019849716

  40. Merrill GF. Acetaminophen and low-flow myocardial ischemia: efficacy and antioxidant mechanisms. J Physiol Heart Circ Physiol. 2002;282(4):H1341-H1349.

  41. Merrill GF, Rork TH, Spiler NM, Golfetti R. Acetaminophen and myocardial infarction in dogs. J Physiol Heart Circ Physiol. 2004;287(5):H1913-H1920.

  42. Merrill GF, Merrill JH, Golfetti R, Jaques KM, Hadzimichalis NS, Baliga SS, et al. Antiarrhythmic properties of acetaminophen in the dog. Exp Biol Med. 2007;232(9):1245-52.

  43. Doyon S, Klein-Schwartz W, Lee S, Beuhler MC. Fatalities involving acetaminophen combination products reported to United States poison centers. Clin Toxicol. 2013;51(10):941-8.

  44. García-Fuertes D, Villanueva-Fernández E, Crespín-Crespín M. 2016. Drug-induced long-QT and torsades de pointes in elderly polymedicated patients. Arq Bras Cardiol. 2016;106(2):156-9.

  45. Merrill GF, Mcconnell P, Vandyke K, Powell S. Coronary and myocardial effects of acetaminophen: protection during ischemia-reperfusion. J Physiol Heart Circ Physio. 2001;280(6):H2631-H2638.

  46. Forrest JA, Clements J, Prescott L. Clinical pharmacokinetics of paracetamol. Clin Pharmacokinet. 1982;7(2):93-107.

  47. Hall JE. Guyton y Hall. Tratado de fisiología médica. Barcelona, España: Elsevier; 2016: p. 3948.

  48. Godfraind T. Discovery and Development of Calcium Channel Blockers. Front Pharmacol. 2017;8:286. DOI: https://doi.org/10.3389/fphar.2017.00286




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