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Vol. 20. Issue 3.
Pages 149-153 (May - June 2013)
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Vol. 20. Issue 3.
Pages 149-153 (May - June 2013)
Open Access
Efectos cardiovasculares de fingolimod en el tratamiento de la esclerosis múltiple
Cardiovascular effects of fingolimod in the treatment of multiple sclerosis
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Miguel A. Urina1,2,
Corresponding author
miguelurina@fundacionbios.org

Correspondencia: carrera 50 No. 80-216, Barranquilla, Colombia.
, Catalina Rojas3, Daniela Urina1
1 Fundación del Caribe para la Investigación Biomédica. Barranquilla, Colombia
2 Universidad Simón Bolivar. Barranquilla, Colombia
3 Novartis. Bogotá, Colombia
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Fingolimod es un medicamento modificador de la enfermedad para pacientes con esclerosis múltiple de tipo recaída remisión; la molécula es un análogo de esfingosina fosfato que debido a su mecanismo de acción, produce en 0,5% de los pacientes, una disminución de la frecuencia cardíaca durante la administración de la primera dosis y un aumento leve de la presión arterial al segundo mes de tratamiento. En este articulo se revisan los mecanismos celulares por los cuales fingolimod causa estos eventos y se reportan recomendaciones de seguridad basados en la US Food and Drug Administration (FDA) para el inicio de pacientes en tratamiento con este medicamento.

Palabras clave:
frecuencia cardiaca ;farmacología

Fingolimod is a disease modifying drug for patients with relapse remitting multiple sclerosis (RRMS). The molecule is a sphingosine phosfate analog that because of its mechanism of action causes a decrease in heart rate during the administration of the first dosis and a slight increase in blood pressure in the second month of treatment in 0.5% of patients. We review in this article the cellular mechanisms by which fingolimod causes these events and report safety recommendations based on US Food and Drug Administration (FDA) for initiating treatment with this drug.

Keywords:
heart rate ;pharmacology
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Bibliografía
[1.]
M. Pugliatti, S. Sotgiu, Rosati G:.
The worldwide prevalence of multiple sclerosis.
Clin Neurol Neurosurg, 104 (2002), pp. 182-191
[2.]
J.L. Sánchez, C. Aguirre, O.M. Arcos-Burgos, J.M. Jiménez, F. León, J. Pareja, et al.
Prevalence of multiple sclerosis in Colombia (in Spanish).
Rev Neurol, 31 (2000), pp. 1101-1103
[3.]
J. Toro, O. Sarmiento, A. Díaz del Castillo, C. Satizábal, J. Ramírez, A.C. Montenegro, et al.
Prevalence of multiple sclerosis in Bogotá. Colombia.
Neuroepidemiology, 28 (2007), pp. 33-38
[4.]
J.A. Cohen, F. Barkhof, G. Comi, H.P. Hartung, B.O. Khatri, X. Montalban, et al.
Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.
N Engl J Med, 362 (2010), pp. 402-415
[5.]
T. Sanchez, T. Hla.
Structural and functional characteristics of S1P receptors.
J Cell Biochem, 92 (2004), pp. 913-922
[6.]
V. Brinkmann.
Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology.
Pharmacol. Ther, 115 (2007), pp. 84-105
[7.]
V. Brinkmann, M. Davis, C. Heise, R. ALbert, S. Cottens, R. Hof, et al.
The immune modulator FTY720 targets sphingosine 1-phosphate receptors.
J. Biol Chem, 277 (2002), pp. 21453-21457
[8.]
S. Mandala, R. Hajdu, J. Bergstrom, E. Quackenbushe, J. Xie, J. Milligan, et al.
Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists.
Science, 296 (2002), pp. 346-349
[9.]
V. Brinkmann, A. Billich, T. Baumruker, P. Heining, R. Schmouder, G. Francis, et al.
Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis.
Nature Reviews, 9 (2010), pp. 883-897
[10.]
L. Koyrakh, M. Roman, V. Brinkmann, K. Wickman.
The hearth rate decrease caused by acute FTY720 administration is mediated by the G protein-gated potassium channel I KACh.
Am J Transplant, 5 (2005), pp. 529-536
[11.]
T. Ivanova-Nokolova, E. Nokolove, C. Hansen, J. Robishaw.
Muscarinic K+ Channel in the Heart.
J Gen Physiol, 112 (1998), pp. 199-210
[12.]
K. Wickman, D. Clapham.
Ion channel regulation by G proteins.
Physiol Rev, 75 (1995), pp. 865-885
[13.]
K.D. Wickman, J.A. Iñiguez-Lluhl, P.A. Davenport, R. Taussig, G.B. Krapivinsky, M.E. Linder, et al.
Recombinant G-protein beta gamma-subunits activates the muscarinicgated atrial potassium channel.
Nature, 368 (1994), pp. 255-257
[14.]
M.G. Sanna, J. Liao, E. Jo, C. Alfonso, M.Y. Ahn, M.S. Peterson, et al.
Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate.
J Biol Chem, 279 (2004), pp. 13839-21348
[15.]
S. Salomone, S. Yoshimura, U. Reuter, M. Foley, S. Thomas, M. Moskowitz, et al.
S1P3 receptors mediate the potent constriction of cerebral arteries by sphingosine-1-phosphate.
Eur J Pharmacol, 469 (2003), pp. 125-134
[16.]
W. Hu, S. Mahavadi, J. Huang, F. Li, K. Murthy.
Characterization of S1P1 and S1P2 receptor function in smooth muscle by receptor silencing and receptor protection.
Am J Physiol Gastrointest Liver Physiol, 291 (2006), pp. 605-610
[17.]
M. Uehata, T. Ishizaki, H. Satoh, T. Ono, T. Kawahara, T. Morishita, et al.
Calcium sensitization of smooth muscle mediated by a Rho-associate protein kinase in hypertension.
Nature, 389 (1997), pp. 990-994
[18.]
M. Tölle, B. Levkau, P. Keul, V. Brinkmann, G. Giebing, G. Schonfelder, et al.
Immunomodulator FTY720 induces eNOS-dependent arterial vasodilatation via the lysophospholipid receptor S1P3.
[19.]
M. Forrest, S.Y. Sun, R. Hajdu, J. Bergstrom, D. Card, G. Doherty, et al.
Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes.
J Pharmacol Exp Ther, 309 (2004), pp. 758-768
[20.]
Pine S, pyne N. Sphingosine 1-phophate signaling via the endothelial differentiation gene family of G-protein-coupled receptors. Pharmacol Ther. 88 (2):115-31.
[21.]
FDA: Fingolimod (marketed as Gilenya) Prescribing and Labeling Information; label approved on 05/09/2012 (PDF) [Consultado: agosto 16 2012]. Disponible en: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist.
Copyright © 2013. Sociedad Colombiana de Cardiología y Cirugía Cardiovascular
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