**Author details**

Omid Mehrpour1\*, Mohammaddavood Sharifi2 and Nasim Zamani3

\*Address all correspondence to: omid.mehrpour@yahoo.com

1 Medical Toxicology and Drug Abuse Research Center, Birjand University of Medical Sciences, Birjand, Iran

2 Department of Emergency medicine, Mashhad University of Medical Sciences, Iran

3 Department of Clinical Toxicology, Loghman Hakim Hospital, Shahid Behehshti University of Medical Sciences, Tehran, Iran

The authors declare that they have no competing interests.

## **References**


[15] Goeringer K, Logan B, Christian G. Identification of tramadol and its metabolites in blood from drug-related deaths and drug-impaired drivers. J Anal Toxicol. 1997;21(7):529-37.

**References**

cal Sciences. 2011;15(1):72-7.

116 Toxicology Studies - Cells, Drugs and Environment

cine journal. 2007;37(12):798-805.

animation. 2011;20(5):436-41.

Toxicology. 2011;5(2).

2012;35(8):e219-e21.

tology. 2006;25(1):9-15.

2009;59(3):178-.

363-74.

Journal of medical toxicology. 2011;7(3):183-8.

medicine and pathology. 1999;20(1):98-100.

tered antidepressants. Psychiatry (Edgmont). 2009;6(4):17.

[1] Ahmadi H, Hosseini J, Rezaei M. Epidemiology of tramadol overdose in Imam Kho‐ meini hospital, Kermanshah, Iran (2008). Journal of Kermansha University of Medi‐

[2] Shamsi Meymandi M, Nakhaee N, Shojaee Baghini M, Mazhari S, Sharifi S, Sharifi F. Evaluation of general practitioners' knowledge about Tramadol, Kerman, 1383. Jour‐

[3] Taghaddosinejad F, Mehrpour O, Afshari R, Seghatoleslami A, Abdollahi M, Dart RC. Factors related to seizure in tramadol poisoning and its blood concentration.

[4] Pearson S, Ringland C, Kelman C, Mant A, Lowinger J, Stark H, et al. Patterns of an‐ algesic and anti inflammatory medicine use by Australian veterans. Internal medi‐

[5] Sansone RA, Sansone LA. Tramadol: seizures, serotonin syndrome, and coadminis‐

[6] Afshari R, Afshar R, Mégarbane B. Tramadol overdose: review of the literature. Ré‐

[7] Goodarzi F, Mehrpour O, Eizadi-Mood N. A study to evaluate factors associated with seizure in Tramadol poisoning in Iran. Indian Journal of Forensic Medicine &

[8] Shadnia S, Soltaninejad K, Heydari K, Sasanian G, Abdollahi M. Tramadol intoxica‐ tion: a review of 114 cases. Human & experimental toxicology. 2008;27(3):201-5. [9] Mazor SS, Feldman KW, Sugar NF, Sotero M. Pediatric tramadol ingestion resulting in seizurelike activity: a case series. Pediatric emergency care. 2008;24(6):380-1. [10] Moore KA, Cina SJ, Jones R, Selby DM, Levine B, Smith ML. Tissue distribution of tramadol and metabolites in an overdose fatality. The American journal of forensic

[11] Cole JB, Sattiraju S, Bilden EF, Asinger RW, Bertog SC. Isolated tramadol overdose associated with Brugada ECG pattern. Pacing and Clinical Electrophysiology.

[12] Shipton E. Tramadol--present and future. Anaesthesia and intensive care. 2000;28(4):

[13] Raffa R. Pharmacological aspects of successful long-term analgesia. Clinical rheuma‐

[14] Afshari R, Ghooshkhanehee H. Tramadol overdose induced seizure, dramatic rise of CPK and acute renal failure. JPMA The Journal of the Pakistan Medical Association.

nal of Kerman University of Medical Sciences. 2005;12(3):202-8 (Persian).


[43] Talaie H, Panahandeh R, Fayaznouri MR, Asadi Z, Abdollahi M. Dose-independent occurrence of seizure with tramadol. Journal of medical toxicology. 2009;5(2):63-7.

[29] Liu X, Song J. [Chronopharmacology of tramadol in mice]. Yao xue xue bao= Acta

[30] Musshoff F, Madea B. Fatality due to ingestion of tramadol alone. Forensic science

[31] Levo A, Koski A, Ojanperä I, Vuori E, Sajantila A. Post-mortem SNP analysis of CYP2D6 gene reveals correlation between genotype and opioid drug (tramadol) me‐

[32] Barbera N, Fisichella M, Bosco A, Indorato F, Spadaro G, Romano G. A suicidal poi‐ soning due to tramadol. A metabolic approach to death investigation. Journal of for‐

[33] Murphy E. Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Anaesthesia and intensive care. 2005;33(3):311-22.

[34] Edmondson M, Duran S, Boothe D, Stewart A, Ravis W. Pharmacokinetics of trama‐ dol and its major metabolites in alpacas following intravenous and oral administra‐

[35] Daubin C, Quentin C, Goullé J-P, Guillotin D, Lehoux P, Lepage O, et al. Refractory shock and asystole related to tramadol overdose. Clinical toxicology. 2007;45(8):

[36] Tobias JD. Seizure after overdose of tramadol. Southern medical journal. 1997;90(8):

[37] Tjäderborn M, Jönsson AK, Hägg S, Ahlner J. Fatal unintentional intoxications with tramadol during 1995–2005. Forensic science international. 2007;173(2):107-11.

[38] 38.Johansson I, Ingelman-Sundberg M. Genetic polymorphism and toxicology—with

[39] Samer CF, Daali Y, Wagner M, Hopfgartner G, Eap CB, Rebsamen M, et al. Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. British journal of

[40] Rollason V, Samer C, Piguet V, Dayer P, Desmeules J. Pharmacogenetics of analge‐

[41] Musshoff F, Madea B, Stuber F, Stamer UM. Enantiomeric determination of tramadol and O-desmethyltramadol by liquid chromatography-mass spectrometry and appli‐ cation to postoperative patients receiving tramadol. Journal of analytical toxicology.

[42] Bergheim M, Gieré R, Kümmerer K. Biodegradability and ecotoxicitiy of tramadol, ranitidine, and their photoderivatives in the aquatic environment. Environmental

emphasis on cytochrome p450. Toxicological Sciences. 2011;120(1):1-13.

tion. Journal of veterinary pharmacology and therapeutics. 2012;35(4):389-96.

tabolite ratios in blood. Forensic science international. 2003;135(1):9-15.

pharmaceutica Sinica. 2001;36(8):561-4.

ensic and legal medicine. 2013;20(5):555-8.

pharmacology. 2010;160(4):919-30.

2006;30(7):463-7.

sics: toward the individualization of prescription. 2008.

Science and Pollution Research. 2012;19(1):72-85.

international. 2001;116(2):197-9.

118 Toxicology Studies - Cells, Drugs and Environment

961-4.

826-7.


[73] Farajidana H, Hassanian-Moghaddam H, Zamani N, Sanaei-Zadeh H. Tramadol-in‐ duced seizures and trauma. Eur Rev Med Pharmacol Sci. 2012;16(Suppl 1):34-7.

[58] Schnitzer TJ. Update of ACR guidelines for osteoarthritis: role of the coxibs. Journal

[59] Raffa RB, Buschmann H, Christoph T, Eichenbaum G, Englberger W, Flores CM, et al. Mechanistic and functional differentiation of tapentadol and tramadol. Expert

[60] Tsai Y-C, Chang P-J, Jou I-M. Direct tramadol application on sciatic nerve inhibits spinal somatosensory evoked potentials in rats. Anesthesia & Analgesia. 2001;92(6):

[61] Rothhammer A, Weis K, Skrobek W. [The clinical usefulness of Tramadol-infusion

[62] Salman M, Sahin A, Onur M, Öge K, Kassab A, Aypar Ü. Tramadol encapsulated in‐ to polyhydroxybutyrate microspheres: in vitro release and epidural analgesic effect

[63] Shirzad H, Dehghanian SL, Yousefi M, Nikookar M, Rafieian M. Effects of tramadol on activity of peritoneal phagocytes in Balb/C mice. ISMJ. 2011;14(4):214-9.

[64] Agrawal A, Diwan S, Mahajan R. Severe delirium following single dose of tramadol.

[65] Garcia J, Altman RD, editors. Chronic pain states: pathophysiology and medical ther‐

[66] In: Goldfrank LR, Flomenbaum N, Lewis NA, Howland MA, Hoffman RS, Nelson LS, editors. Goldfrank's Toxicologic Emergencies. 7 ed. New York: McGraw-Hill

[67] Sanaei-Zadeh H. Tramadol intoxication and shoulder pain. European review for

[68] Lofwall MR, Babalonis S, Nuzzo PA, Siegel A, Campbell C, Walsh SL. Efficacy of ex‐ tended-release tramadol for treatment of prescription opioid withdrawal: a two-

[69] El-Naggar M, El-Sehly WM, Morad GM, Eeed M, Hassan M. P19: The toxic effect of prolonged Ultram administration on cerebral cortex of albino rats: Toxicological and

[70] Loughrey M, Loughrey C, Johnston S, O'Rourke D. Fatal hepatic failure following ac‐ cidental tramadol overdose. Forensic science international. 2003;134(2):232-3.

[71] Jick H, Derby LE, Vasilakis C, Fife D. The risk of seizures associated with tramadol. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy.

[72] Gasse M, Derby L, Vasilakis Scaramozza C, Jick H. Incidence of FirstTime Idiopathic Seizures in Users of Tramadol. Pharmacotherapy: The Journal of Human Pharmacol‐

phase randomized controlled trial. Drug Alcohol Depend. 2013;133(1):188-97.

histological study. Experimental and Toxicologic Pathology. 2009;61(3):290.

anaesthesia (author's transl)]. Der Anaesthesist. 1981;30(12):619-22.

in rats. Acta anaesthesiologica scandinavica. 2003;47(8):1006-12.

Indian journal of medical sciences. 2009;63(2):80-1.

apy. Seminars in arthritis and rheumatism; 1997: Elsevier.

medical and pharmacological sciences. 2014;18(2):285.

of pain and symptom management. 2002;23(4):S24-S30.

Opin Pharmacother. 2012;13(10):1437-49.

1547-51.

120 Toxicology Studies - Cells, Drugs and Environment

Medical; 2000:916

1998;18(3):607-11.

ogy and Drug Therapy. 2000;20(6):629-34.


[100] Pilgrim J, Gerostamoulos D, Drummer OH. Deaths involving serotonergic drugs. Forensic science international. 2010;198(1):110-7.

[86] Garrett P. Tramadol overdose and serotonin syndrome manifesting as acute right

[87] Hallberg P, Brenning G. Angioedema induced by tramadol—a potentially life-threat‐ ening condition. European journal of clinical pharmacology. 2005;60(12):901-3.

[88] De Decker K, Cordonnier J, Jacobs W, Coucke V, Schepens P, Jorens PG. Fatal intoxi‐ cation due to tramadol alone: case report and review of the literature. Forensic sci‐

[89] Stamer UM, Stüber F, Muders T, Musshoff F. Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication. Anesthesia & An‐

[90] Aronson MD. Nonsteroidal anti-inflammatory drugs, traditional opioids, and trama‐ dol: constrating therapies for the treatment of chronic pain. Clinical therapeutics.

[91] Atici S, Cinel I, Cinel L, Doruk N, Eskandari G, Oral U. Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. Journal of bio‐

[92] Tolman KG. Hepatotoxicity of non-narcotic analgesics. Am J Med. 1998;105(1b):

[93] Mugunthan N, Davoren P. Danger of Hypoglycemia Due to Acute Tramadol Poison‐

[94] Petrone D, Kamin M, Olson W. Slowing the titration rate of tramadol HCl reduces the incidence of discontinuation due to nausea and/or vomiting: a double-blind

[95] Le TH, Lim ES, Lee SK, Park JS, Kim YH, Min J. Toxicity evaluation of verapamil and tramadol based on toxicity assay and expression patterns of Dhb, Vtg, Arnt, CYP4,

[96] El-Okdi NS, Lumbrezer D, Karanovic D, Ghose A, Assaly R. Serotonin Syndrome Af‐ ter the Use of Tramadol and Ziprasidone in a Patient With a Deep Brain Stimulator

[97] Lange-Asschenfeldt C, Weigmann H, Hiemke C, Mann K. Serotonin syndrome as a result of fluoxetine in a patient with tramadol abuse: plasma level-correlated sympto‐

[98] Hernandez AF, Montero MN, Pla A, Villanueva E. Fatal moclobemide overdose or

[99] Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol and

death caused by serotonin syndrome? Journal of forensic sciences. 1995.

sertraline coadministration. Ann Pharmacother. 1997;31(2):175-7.

and CYP314 in Daphnia magna. Environmental toxicology. 2011;26(5):515-23.

heart dysfunction. Anaesthesia and intensive care. 2004;32(4):575-7.

ence international. 2008;175(1):79-82.

algesia. 2008;107(3):926-9.

122 Toxicology Studies - Cells, Drugs and Environment

sciences. 2005;30(2):245-52.

ing. Endocrine Practice. 2012;18(6):e151-e2.

for Parkinson Disease. Am J Ther. 2013.

randomized trial. J Clin Pharm Ther. 1999;24(2):115-23.

matology. J Clin Psychopharmacol. 2002;22(4):440-1.

1997;19(3):420-32.

13s-9s.


[127] Mehrpour O. Addiction and seizure ability of tramadol in high-risk patients. Indian J Anaesth. 2013;57(1):86-7.

[114] Klingmann A, Skopp G, Pedal I, Poetsch L, Aderjan R. [Distribution of morphine and morphine glucuronides in body tissue and fluids--postmortem findings in brief sur‐

[115] Mannocchi G, Napoleoni F, Napoletano S, Pantano F, Santoni M, Tittarelli R, et al. Fatal self administration of tramadol and propofol: A case report. Journal of forensic

[116] Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. Journal

[117] Zhang S, Guan DW, Wang L, Wang HX, Zhang GH, Zhao R, et al. [The expression of GABA(A) receptor alpha1 and GABA(B) receptor 1 in medulla oblongata solitary nu‐ cleus and ambiguous nucleus in the cases of tramadol intoxication]. Fa Yi Xue Za

[118] Tramadol oral solution: new drug. Poorly evaluated and potentially dangerous in

[119] Riedel F, Stockhausen H-Bv. Severe cerebral depression after intoxication with tra‐ madol in a 6-month-old infant. European journal of clinical pharmacology.

[120] Hendrickson RG, McKeown NJ. Is maternal opioid use hazardous to breast-fed in‐

[121] Maréchal C, Honorat R, Claudet I. Serotonin syndrome induced by tramadol intoxi‐

[122] Raffa RB, Wu C, Stone Jr DJ, Borenstein MR, Codd EE, Coogan TP. Determination of the adsorption of tramadol hydrochloride by activated charcoal in vitro and in vivo.

[123] Saidi H, Ghadiri M, Abbasi S, Ahmadi S-F. Efficacy and safety of naloxone in the management of postseizure complaints of tramadol intoxicated patients: a self-con‐

[124] Vahabzadeh M, Moshiri M, Mohammadpour AH, Hosseinzadeh H. Promising ef‐ fects of intravenous lipid emulsion as an antidote in acute tramadol poisoning. Re‐

[125] Zhang M, Jing L, Liu Q, Wen RT, Li JX, Li YL, et al. Tramadol induces conditioned place preference in rats: interactions with morphine and buprenorphine. Neurosci

[126] McDiarmid T, Mackler L. What is the addiction risk associated with tramadol? Clini‐

cation in an 8-month-old infant. Pediatric neurology. 2011;44(1):72-4.

Journal of pharmacological and toxicological methods. 2000;43(3):205-10.

trolled study. Emergency Medicine Journal. 2010;27(12):928-30.

gional anesthesia and pain medicine. 2013;38(5):425-30.

vival]. Archiv fur Kriminologie. 1999;206(1-2):38-49.

and legal medicine. 2013;20(6):715-9.

of analytical toxicology. 2011;35(4):242-7.

children. Prescrire Int. 2005;14(77):83-5.

fants? Clinical Toxicology. 2012;50(1):1-14.

Zhi. 2011;27(6):401-4.

124 Toxicology Studies - Cells, Drugs and Environment

1984;26(5):631-2.

Lett. 2012;520(1):87-91.

cal Inquiries, 2005 (MU). 2005.

