26 Noviembre

Mecanismo de Acción del Paracetamol: Investigaciones recientes.

El Paracetamol es uno de los analgésicos y antipiréticos de venta libre  más populares en el mundo. Aunque fue descubierto hace más de 100 años y usado ampliamente por más de 50 años su mecanismo de acción es aún motivo de debate.

En 1972, los farmacólogos ingleses Roderick J. Flowner y John R. Vane (Premio Nobel 1982), descubrieron que actúa centralmente como un inhibidor débil de la síntesis de prostaglandina por la COX-1 y COX-2. Estos hallazgos prevalecieron por más de 3 décadas.

 

Recientes hallazgos sugieren que el paracetamol  tiene actividad periférica en la síntesis de prostaglandina. El 2007 y el 2008, dos estudios de investigación liderados por Lee y Hinz respectivamente, sugirieron  que el paracetamol inhibe  selectivamente la COX-2 a nivel periférico. Ahora sabemos que bloquea la síntesis de prostaglandina, a nivel central y periférico, mediante la inhibición tanto de la COX-1 como de la COX-2 debe considerarse la posibilidad de efectos cardiovasculares de los COX-2 en el uso prolongado de paracetamol.

Existen otros mecanismos posibles que están siendo investigados. Los efectos antinociceptivos del paracetamol han sido vinculados a los sistemas serotoninérgico, canabinoide, y opioide. Además se está postulando la inhibición de neurotransmisores a nivel del sistema nervioso central. Otra hipótesis sobre el efecto analgésico de paracetamol se centra en su metabolito activo AM404 que es  un acido lipoamino especifico del cerebro que inhibe la producción de prostaglandinas en ratas. Estos hallazgos aun son controversiales porque no se solo se han realizado en modelos animales.

 

Referencias 

Flower RJ, Vane JR.Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol).  Nature. 1972 Dec 15;240(5381):410-1.

Aminoshariae A, Khan A. Acetaminophen: old drug, new issues. J Endod. 2015 May;41(5):588-93.

Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J. 2008 Feb;22(2):383-90.

Lee YS, Kim H, Brahim JS, Rowan J, Lee G, Dionne RA. Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation. Pain. 2007 Jun;129(3):279-86.

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