Evaluation of cardiac injury biomarkers in serum following concomitant administration of sildenafil citrate with dextromethorphan and chlorpheniramine in rat
Subject Areas :
Veterinary Clinical Pathology
Rasol
Sadeghy
1
(Gratuate of Veterinary Medicine, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran)
B.
Amouoghli Tabrizi
2
(Associate Professor, Department of Clinical Science, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran)
majid
fartashvand
3
(Assistant Professor, Department of Clinical Sciences, Faculty of Veterinary Medicine, Islamic Azad University, Tabriz Branch)
Received: 2021-01-30
Accepted : 2021-04-06
Published : 2021-01-20
Keywords:
Cardiac troponin I,
Sildenafil citrate,
dextromethorphan,
chlorpheniramine,
heart damage,
Abstract :
Sildenafil citrate is an inhibitor of the enzyme phosphodiesterase 5, dextromethorphan is an antitussive with weak opioid effects, and chlorpheniramine is a first-generation antihistamine. Since cardiovascular complications related to all three drugs have been reported, the aim of this study was to evaluate the serum levels of cardiac damage index enzymes and tropovinin I following co-administration of sildenafil with dextromethorphan and chlorpheniramine. Forty male Wistar rats were studied in 8 groups, one control group and the rest in the treatment group; Drugs sildenafil citrate (100 mg / kg), dextromethorphan (20 mg / kg), chlorpheniramine (20 mg / kg), dextromethorphan + chlorpheniramine, sildenafil + dextromethorphan, sildenafil + chlorpheniramine, sildenafil + rosemethor + dextrometer , Received food. The results showed that administration of sildenafil to rats did not cause statistically significant changes in serum cardiac injury indices compared with the control group (p < 0.05); The amount of CK-MB also decreased compared to the control group. On the other hand, following administration of chlorpheniramine and dextromethorphan to rats, either alone or in combination, serum levels of AST, LDH and CK-MB increased statistically significantly. Administration of chlorpheniramine caused a significant increase in LDH (p < 0.01) and CK-MB (p < 0.001) compared to the control group and administration of dextromethorphan increased the activity of the studied enzymes which increased AST (p < 0.05). ) And CK-MB (p < 0.001) were significant. Co-administration of sildenafil with dextromethorphan and sildenafil with chlorpheniramine or all three together increased the activity of all three enzymes in the heart damage index.
References:
Al–Toma, F.J. and Dawood, M.S. (2008). Behavior of Creatine Kinase Isoenzymes in Hepatic Diseases. Kufa Medical Journal, 11(1): 501-507.
Babuin, L. and Jaffe. A.S. (2005). Troponin: the biomarker of choice for the detection of cardiac injury. Canadian Medical Association Journal, 173(10): 1191-1202.
Benedict, N., Seybert, A. and Mathier, M.A. (2007). Evidence-based pharmacologic management of pulmonary arterial hypertension. Clinical Therapeutics, 29(10): 2134-35.
Boyce, G. and Umland, M. (2001). Sildenafil Citrate: A Therapeutic Update. Clinical Therapeutics, 23(1): 1-22.
Chen, S.L., Huang, E.Y.K., Chow, L.H. and Tao, P.L. (2005). Dextromethorphan differentially affects opioid antinociception in rats. British Journal of Pharmacology, 144(3): 400-404.
Chyka, P.A., Erdman, A.R., Manoguerra, A.S., Christianson, G., Booze, L.L., Nelson, L.S. et al. (2007). Dextromethorphan poisoning: an evidence-based consensus guideline for out-of-hospital management. Clinical Toxicology, 45(6): 662-667.
Colahan, P.T., Jackson, C.A., Rice, B., Szabo, N. and Jones, J.H. (2010). The effect of sildenafil citrate administration on selected physiological parameters of exercising Thoroughbred horses. Equine Veterinary Journal, 42: 606-612
Dhariwal, A.K. and Bavdekar, S.B. (2015). Sildenafil in pediatric pulmonary arterial hypertension. Journal of Postgraduate Medicine, 61(3): 181-192.
Di Stolfo, G., Accadia, M., Mastroianno, S., Leone, M.P., Palumbo, O., Palumbo, P. et al. (2019). Long QT syndrome in chromosome 7q35q36.3 deletion involving KCNH2 gene: Warning for chlorpheniramine prescription. Molecular Genetics & Genomic Medicine, 7(9): e855.
Falcón-Chévere, J.L., Cabañas, J.G., Canales-Colón, I. and Martorell-Millan, G. (2007). Sildenafil citrate and Torsade de pointes. Boletin de la Asociacion Medica de Puerto Rico, 99(4): 325-30.
Fiocchi, R., Gori, M., Taddi, F., Trevisani, L., Gallo, M. and Eleftheriou, G. (2019). Cardiac toxicity of combined vemurafenib and cobimetinib administration. International Journal of Clinical Pharmacology and Therapeutics, 57(5): 259-263.
Gerometta, R., Alvarez, L.J. and Candia, O.A. (2012). Sildenafil accelerates anterior chamber refilling after paracentesis in sheep and rabbits. Investigative Ophthalmology & Visual Science, 53(2): 565-573.
Hasanein, P. (2009). Effects of chlorpheniramine and hydroxyzine administration, as histamine H1- receptor antagonists, on the nociception threshold of cholestatic rats. Hormozgan Medical Journal, 13(3): 173-181. [In Persian]
Hong, H.K. and Jo, S.H. (2009). Block of hERG K+ channel by classic histamine H1 receptor antagonist chlorpheniramine. The Korean Journal of Physiology & Pharmacology, 13(3): 215-220.
Huang, S.A. and Lie, J.D. (2013). Phosphodiesterase-5 (PDE5) Inhibitors in the Management of Erectile Dysfunction. Pharmacy and Therapeutics, 38(7): 407.
Ichinose, F., Erana-Garcia, J., Hromi, J., Raveh, Y., Jones, R., Krim, L. et al. (2001). Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension. Critical Care Medicine, 29(5): 1000-1005.
Jackson, G., Gillies, H., Osterloh, I. (2005). Past, present, and future: a 7-year update of Viagra (sildenafil citrate). International Journal of Clinical Practice, 59(6): 680-691.
Jamshidzadeh, A. and Azarpira, N. (2011). The Effects of Topical Sildenafil on Wound Healing in Rat. Iranian Journal of Pharmaceutical Sciences, 7(1): 43-48.
Kamei, C., Ohuchi, M., Sugimoto, Y. and Okuma, C. (2000). Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats. Brain Research, 887(1): 183-186.
Kane, L.B. and Klings, E.S. (2006). Present and future treatment strategies for pulmonary arterial hypertension: focus on phosphodiesterase-5 inhibitors. Treatments in Respiratory Medicine, 5(4): 271-282.
Kaplan, B., Buchanan, J. and Krantz, M.J. (2011). QTc prolongation due to dextromethorphan. International Journal of Cardiology, 148(3): 363.
Krantz, M.J., Martin, J., Stimmel, B., Mehta, D. and Haigney, M.C.P. (2009). QTc interval screening and methadone treatment. Annals of Internal Medicine, 150(6): 387-95.
Krantz, M.J., Palmer, R.B. and Haigney, M.C.P. (2021). Cardiovascular Complications of Opioid Use. Journals of the American College of Cardiology, 77(2): 205-23.
Leibovitch, L., Matok, I. and Paret, G. (2007). Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension. Drugs, 67(1): 57-73
Li, M. and Ramos, L.G. (2017). Drug-Induced QT Prolongation and Torsades de Pointes. Pharmacy and Therapeutics, 42(7): 473-477.
Liu, H., Zheng, Q. and Farley, J.M. (2006). Antimuscarinic actions of antihistamines on the heart. Journal of Biomedical Science, 13(3): 395-401.
Martin, L.L. and Heins, J.R. (2017). Assessing Risk Factors for Torsades de Pointes. South Dakota Medicine, 70(3): 135-137.
Martínez, L. and González, G. (2018). Cardiotoxicity of H1-antihistamines. Journal of Analytical & Pharmaceutical Research, 7(2): 197-201.
Moreira, Jr.S.G., Brannigan, R.E., Spitz, A., Orejuela, F.J., Lipshultz, L.I. and Kim, E.D. (2000). Side-effect profile of sildenafil citrate (Viagra) in clinical practice. Urology, 56(3): 474-476.
Nia, A.M., Fuhr, U., Gassanov, N., Erdmann, E. and Er, F. (2010). Torsades de pointes tachycardia induced by common cold compound medication containing chlorpheniramine. European Journal of Clinical Pharmacology, 66(11): 1173-1175.
Noori, S., Friedlich, P., Wong, P., Garingo, A. and Seri, I. (2007). Cardiovascular effects of sildenafil in neonates and infants with congenital diaphragmatic hernia and pulmonary hypertension. Neonatology, 91(2): 92-100.
O’Brien, P.J., Landt, Y. and Ladenson, J.H. (1997). Differential reactivity of cardiac and skeletal muscle from various species in a cardiac troponin I immunoassay. Clinical Chemistry, 43(12): 2333-2338.
Ösken, A., Yelgeç, N.S., Zehir, R., Kemaloğlu Öz, T., Yaylacı, S., Akdemir, R. et al. (2016). Torsades de pointes induced by concomitant use of chlorpheniramine and propranolol: An unusual presentation with no QT prolongation. Indian Journal of Pharmacology, 48(4): 462-465.
Richalet, J.P., Gratadour, P., Robach, P., Pham, I., Déchaux, M., Joncquiert-Latarjet, A., et al. (2005). Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension. American Journal of Respiratory and Critical Care Medicine, 171(3): 275-281.
Shin, H.S., Bae, S.K. and Lee, M.G. (2006): Pharmacokinetics of sildenafil after intraveno- us and oral administration in rats: hepatic and intestinal first-pass effects. International Journal of Pharmaceutics, 320(1-2): 64-70.
Silva, A.R. and Dinis-Oliveira R.J. (2020). Pharmacokinetics and pharmacodynamics of dextromethorphan: clinical and forensic aspects. Drug Metabolism Review, 52(2): 258-282.
Soldovieri, M.V., Miceli, F. and Taglialatela, M. (2008). Cardiotoxic effects of antihistamines: from basics to clinics (...and back). Chemical Research in Toxicology, 21(5): 997-1004.
Tisdale, J.E. (2016). Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Canadian Pharmacists Journal, 149(3): 139-152.
Weimann, J., Ullrich, R., Hromi, J., Fujino, Y., Clark, M.W., Bloch, K.D., et al. (2000). Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension. Anesthesiology, 92(6): 1702-1712.
Yang, H.H., Hou, C.C., Lin, M.T. and Chang, C.P., (2012). Attenuating heat-induced acute lung inflammation and injury by dextromethorphan in rats. American Journal of Respiratory Cell and Molecular Biology, 46(3): 407-413
Yu, S., Gao, Y., Walline, J.H., Lu, X., Zhao, L. and Li, L. (2021). Role of anti-allergic agents on attenuating transfusion reactions in adults: A systematic review and meta-analysis. Transfusion and Apheresis Science, 60(2): 103041.
Zarini, E., Amouoghli Tabrizi, B., Fartashvand, M. and Sadeghy, R. (2014). Effects of Long-term administration of sildenafil citrate on serum markers of cardiac injury in the rats. Journal of Comparative Pathobiology, 11(3): 1357-1362. [In Persian]
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Al–Toma, F.J. and Dawood, M.S. (2008). Behavior of Creatine Kinase Isoenzymes in Hepatic Diseases. Kufa Medical Journal, 11(1): 501-507.
Babuin, L. and Jaffe. A.S. (2005). Troponin: the biomarker of choice for the detection of cardiac injury. Canadian Medical Association Journal, 173(10): 1191-1202.
Benedict, N., Seybert, A. and Mathier, M.A. (2007). Evidence-based pharmacologic management of pulmonary arterial hypertension. Clinical Therapeutics, 29(10): 2134-35.
Boyce, G. and Umland, M. (2001). Sildenafil Citrate: A Therapeutic Update. Clinical Therapeutics, 23(1): 1-22.
Chen, S.L., Huang, E.Y.K., Chow, L.H. and Tao, P.L. (2005). Dextromethorphan differentially affects opioid antinociception in rats. British Journal of Pharmacology, 144(3): 400-404.
Chyka, P.A., Erdman, A.R., Manoguerra, A.S., Christianson, G., Booze, L.L., Nelson, L.S. et al. (2007). Dextromethorphan poisoning: an evidence-based consensus guideline for out-of-hospital management. Clinical Toxicology, 45(6): 662-667.
Colahan, P.T., Jackson, C.A., Rice, B., Szabo, N. and Jones, J.H. (2010). The effect of sildenafil citrate administration on selected physiological parameters of exercising Thoroughbred horses. Equine Veterinary Journal, 42: 606-612
Dhariwal, A.K. and Bavdekar, S.B. (2015). Sildenafil in pediatric pulmonary arterial hypertension. Journal of Postgraduate Medicine, 61(3): 181-192.
Di Stolfo, G., Accadia, M., Mastroianno, S., Leone, M.P., Palumbo, O., Palumbo, P. et al. (2019). Long QT syndrome in chromosome 7q35q36.3 deletion involving KCNH2 gene: Warning for chlorpheniramine prescription. Molecular Genetics & Genomic Medicine, 7(9): e855.
Falcón-Chévere, J.L., Cabañas, J.G., Canales-Colón, I. and Martorell-Millan, G. (2007). Sildenafil citrate and Torsade de pointes. Boletin de la Asociacion Medica de Puerto Rico, 99(4): 325-30.
Fiocchi, R., Gori, M., Taddi, F., Trevisani, L., Gallo, M. and Eleftheriou, G. (2019). Cardiac toxicity of combined vemurafenib and cobimetinib administration. International Journal of Clinical Pharmacology and Therapeutics, 57(5): 259-263.
Gerometta, R., Alvarez, L.J. and Candia, O.A. (2012). Sildenafil accelerates anterior chamber refilling after paracentesis in sheep and rabbits. Investigative Ophthalmology & Visual Science, 53(2): 565-573.
Hasanein, P. (2009). Effects of chlorpheniramine and hydroxyzine administration, as histamine H1- receptor antagonists, on the nociception threshold of cholestatic rats. Hormozgan Medical Journal, 13(3): 173-181. [In Persian]
Hong, H.K. and Jo, S.H. (2009). Block of hERG K+ channel by classic histamine H1 receptor antagonist chlorpheniramine. The Korean Journal of Physiology & Pharmacology, 13(3): 215-220.
Huang, S.A. and Lie, J.D. (2013). Phosphodiesterase-5 (PDE5) Inhibitors in the Management of Erectile Dysfunction. Pharmacy and Therapeutics, 38(7): 407.
Ichinose, F., Erana-Garcia, J., Hromi, J., Raveh, Y., Jones, R., Krim, L. et al. (2001). Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension. Critical Care Medicine, 29(5): 1000-1005.
Jackson, G., Gillies, H., Osterloh, I. (2005). Past, present, and future: a 7-year update of Viagra (sildenafil citrate). International Journal of Clinical Practice, 59(6): 680-691.
Jamshidzadeh, A. and Azarpira, N. (2011). The Effects of Topical Sildenafil on Wound Healing in Rat. Iranian Journal of Pharmaceutical Sciences, 7(1): 43-48.
Kamei, C., Ohuchi, M., Sugimoto, Y. and Okuma, C. (2000). Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats. Brain Research, 887(1): 183-186.
Kane, L.B. and Klings, E.S. (2006). Present and future treatment strategies for pulmonary arterial hypertension: focus on phosphodiesterase-5 inhibitors. Treatments in Respiratory Medicine, 5(4): 271-282.
Kaplan, B., Buchanan, J. and Krantz, M.J. (2011). QTc prolongation due to dextromethorphan. International Journal of Cardiology, 148(3): 363.
Krantz, M.J., Martin, J., Stimmel, B., Mehta, D. and Haigney, M.C.P. (2009). QTc interval screening and methadone treatment. Annals of Internal Medicine, 150(6): 387-95.
Krantz, M.J., Palmer, R.B. and Haigney, M.C.P. (2021). Cardiovascular Complications of Opioid Use. Journals of the American College of Cardiology, 77(2): 205-23.
Leibovitch, L., Matok, I. and Paret, G. (2007). Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension. Drugs, 67(1): 57-73
Li, M. and Ramos, L.G. (2017). Drug-Induced QT Prolongation and Torsades de Pointes. Pharmacy and Therapeutics, 42(7): 473-477.
Liu, H., Zheng, Q. and Farley, J.M. (2006). Antimuscarinic actions of antihistamines on the heart. Journal of Biomedical Science, 13(3): 395-401.
Martin, L.L. and Heins, J.R. (2017). Assessing Risk Factors for Torsades de Pointes. South Dakota Medicine, 70(3): 135-137.
Martínez, L. and González, G. (2018). Cardiotoxicity of H1-antihistamines. Journal of Analytical & Pharmaceutical Research, 7(2): 197-201.
Moreira, Jr.S.G., Brannigan, R.E., Spitz, A., Orejuela, F.J., Lipshultz, L.I. and Kim, E.D. (2000). Side-effect profile of sildenafil citrate (Viagra) in clinical practice. Urology, 56(3): 474-476.
Nia, A.M., Fuhr, U., Gassanov, N., Erdmann, E. and Er, F. (2010). Torsades de pointes tachycardia induced by common cold compound medication containing chlorpheniramine. European Journal of Clinical Pharmacology, 66(11): 1173-1175.
Noori, S., Friedlich, P., Wong, P., Garingo, A. and Seri, I. (2007). Cardiovascular effects of sildenafil in neonates and infants with congenital diaphragmatic hernia and pulmonary hypertension. Neonatology, 91(2): 92-100.
O’Brien, P.J., Landt, Y. and Ladenson, J.H. (1997). Differential reactivity of cardiac and skeletal muscle from various species in a cardiac troponin I immunoassay. Clinical Chemistry, 43(12): 2333-2338.
Ösken, A., Yelgeç, N.S., Zehir, R., Kemaloğlu Öz, T., Yaylacı, S., Akdemir, R. et al. (2016). Torsades de pointes induced by concomitant use of chlorpheniramine and propranolol: An unusual presentation with no QT prolongation. Indian Journal of Pharmacology, 48(4): 462-465.
Richalet, J.P., Gratadour, P., Robach, P., Pham, I., Déchaux, M., Joncquiert-Latarjet, A., et al. (2005). Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension. American Journal of Respiratory and Critical Care Medicine, 171(3): 275-281.
Shin, H.S., Bae, S.K. and Lee, M.G. (2006): Pharmacokinetics of sildenafil after intraveno- us and oral administration in rats: hepatic and intestinal first-pass effects. International Journal of Pharmaceutics, 320(1-2): 64-70.
Silva, A.R. and Dinis-Oliveira R.J. (2020). Pharmacokinetics and pharmacodynamics of dextromethorphan: clinical and forensic aspects. Drug Metabolism Review, 52(2): 258-282.
Soldovieri, M.V., Miceli, F. and Taglialatela, M. (2008). Cardiotoxic effects of antihistamines: from basics to clinics (...and back). Chemical Research in Toxicology, 21(5): 997-1004.
Tisdale, J.E. (2016). Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Canadian Pharmacists Journal, 149(3): 139-152.
Weimann, J., Ullrich, R., Hromi, J., Fujino, Y., Clark, M.W., Bloch, K.D., et al. (2000). Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension. Anesthesiology, 92(6): 1702-1712.
Yang, H.H., Hou, C.C., Lin, M.T. and Chang, C.P., (2012). Attenuating heat-induced acute lung inflammation and injury by dextromethorphan in rats. American Journal of Respiratory Cell and Molecular Biology, 46(3): 407-413
Yu, S., Gao, Y., Walline, J.H., Lu, X., Zhao, L. and Li, L. (2021). Role of anti-allergic agents on attenuating transfusion reactions in adults: A systematic review and meta-analysis. Transfusion and Apheresis Science, 60(2): 103041.
Zarini, E., Amouoghli Tabrizi, B., Fartashvand, M. and Sadeghy, R. (2014). Effects of Long-term administration of sildenafil citrate on serum markers of cardiac injury in the rats. Journal of Comparative Pathobiology, 11(3): 1357-1362. [In Persian]
