Seizures in tramadol overdoses reported in the ToxIC registry: predisposing factors and the role of naloxone

Murray, Brian Patrick; Carpenter, Joseph; Dunkley, Camille A; Moran, Tim P.; Alfaifi, Musa; Alsukaiti, Waleed S; Kazzi, Ziad

doi:10.1080/15563650.2018.1547826

Cited by 18 publications

(9 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our rat model reliably reproduced tramadol toxicity observed in humans, including sedation, hypothermia and seizures [ 4 , 5 , 10 ]. As previously published [ 16 ], our tramadol-overdosed rats exhibited early-onset seizures occurring as soon as 5 min after tramadol injection and disappearing 45 min later.…”

Section: Discussionmentioning

confidence: 89%

“…Tramadol overdose typically results in isolated, brief, self-limiting generalized tonic-clonic seizures, often occurring within 4–6 h post-ingestion, although electroencephalogram abnormalities and recurrent seizures or status epilepticus are not rare [ 5 , 7 , 8 , 9 ]. Based on the Toxicology Investigators Consortium data registry, tramadol-induced seizures were more likely observed in Asian patients and patients abusing or misusing the medication [ 10 ]. A recent systematic review showed that the occurrence of seizures in patients exposed to tramadol is dose-dependent and related to male gender but not to naloxone administration used to reverse coma and respiratory depression [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat

et al. 2022

View full text Add to dashboard Cite

Tramadol overdose is frequently associated with the onset of seizures, usually considered as serotonin syndrome manifestations. Recently, the serotoninergic mechanism of tramadol-attributed seizures has been questioned. This study’s aim was to identify the mechanisms involved in tramadol-induced seizures in overdose in rats. The investigations included (1) the effects of specific pretreatments on tramadol-induced seizure onset and brain monoamine concentrations, (2) the interaction between tramadol and γ-aminobutyric acid (GABA)A receptors in vivo in the brain using positron emission tomography (PET) imaging and 11C-flumazenil. Diazepam abolished tramadol-induced seizures, in contrast to naloxone, cyproheptadine and fexofenadine pretreatments. Despite seizure abolishment, diazepam significantly enhanced tramadol-induced increase in the brain serotonin (p < 0.01), histamine (p < 0.01), dopamine (p < 0.05) and norepinephrine (p < 0.05). No displacement of 11C-flumazenil brain kinetics was observed following tramadol administration in contrast to diazepam, suggesting that the observed interaction was not related to a competitive mechanism between tramadol and flumazenil at the benzodiazepine-binding site. Our findings do not support the involvement of serotoninergic, histaminergic, dopaminergic, norepinephrine or opioidergic pathways in tramadol-induced seizures in overdose, but they strongly suggest a tramadol-induced allosteric change of the benzodiazepine-binding site of GABAA receptors. Management of tramadol-poisoned patients should take into account that tramadol-induced seizures are mainly related to a GABAergic pathway.

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Opioid toxidrome was also found in some of our patients, which manifested as coma, respiratory depression, and/or miosis. This toxidrome could be attributed to the effects of tramadol [ 12 , 24 ]. Seizures observed in a minority of patients (14.1 %) may also result from tramadol-induced sympathomimetic toxidrome or the presence of penitrem A, a powerful neurotoxin [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Acute Toxic Effects of the New Psychoactive Substance “Voodoo” among Patients presented to the Poison Control Center of Ain Shams University Hospitals (PCC-ASUH), Egypt, during 2017

Hussien

Shinawi

El-Hariri

et al. 2021

Subst Abuse Treat Prev Policy

View full text Add to dashboard Cite

Background Voodoo is a heterogeneous mixture of psychoactive substances that has recently grown in popularity among youth in Egypt. Patients can present with a variety of manifestations that may lead to death in some cases. This study assessed the acute toxic effects of voodoo among patients presented to the Poison Control Center of Ain Shams University Hospitals (PCC-ASUH) during a one year period. Methods This is a retrospective study of all patients presented with voodoo intoxication at the PCC-ASUH from 1 January 2017 to 31 December 2017. Clinical data, routine laboratory findings, and ECG results as well as duration of hospitalization and outcome were compiled from hospital records. Results Seventy-one voodoo intoxication cases meeting the inclusion criteria were analyzed (mean age: 25.19 ± 9.54 years, range: 15–50 years, 97.2 % male). Pulse, blood pressure, and respiratory rate were normal in more than half of all patients. Neurological abnormalities including agitation, hallucinations, disturbance of consciousness were the most frequent manifestations. Respiratory acidosis was the most common laboratory finding (54.9 %), followed by increased serum urea (43.6 %), hypokalemia (33.8 %), hyperglycemia (28.1 %), and leukocytosis (26.7 %). The most common ECG finding was sinus tachycardia (31 %), followed by QT prolongation (15.4 %). More than half of the studied patients (53.5 %) co-administered other illicit substances, most frequently cannabis and tramadol. Most patients recovered fully and were discharged, but death occurred in two cases. Conclusions Voodoo toxicity can manifest with many presentations, hampering timely diagnosis. Clinicians should consider possible voodoo poisoning in patients presenting with a history of drug use with neurological symptoms, and they should conduct follow-up arterial blood gases, electrolytes and ECG as voodoo may contain potentially fatal psychoactive substances.

show abstract

“…Respiratory depression can develop within minutes of an opioid injection, inhalation, or insufflation, whereas it can take longer with an oral overdose to reach systemic circulation and cross the blood‐brain barrier 149 . Certain opioids are associated with an increased risk of seizures, including tramadol, morphine, and meperidine 150–152 . The natural opiates, particularly morphine, are histaminergic, which may result in nonimmunogenic allergic symptoms, including urticaria and hypotension 39,153 .…”

Section: Acute Toxicitymentioning

confidence: 99%

Clinical Pharmacology, Toxicity, and Abuse Potential of Opioids

Vearrier

Grundmann

2021

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Opioids were the most common drug class resulting in overdose deaths in the United States in 2019. Widespread clinical use of prescription opioids for moderate to severe pain contributed to the ongoing opioid epidemic with the subsequent emergence of fentanyl‐laced heroin. More potent analogues of fentanyl and structurally diverse opioid receptor agonists such as AH‐7921 and MT‐45 are fueling an increasingly diverse illicit opioid supply. Overdose from synthetic opioids with high binding affinities may not respond to a typical naloxone dose, thereby rendering autoinjectors less effective, requiring higher antagonist doses or resulting in a confusing clinical picture for health care providers. Nonscheduled opioid drugs such as loperamide and dextromethorphan are associated with dependence and risk of overdose as easier access makes them attractive to opioid users. Despite a common opioid‐mediated pathway, several opioids present with unique pharmacodynamic properties leading to acute toxicity and dependence development. Pharmacokinetic considerations involve half‐life of the parent opioid and its metabolites as well as resulting toxicity, as is established for tramadol, codeine, and oxycodone. Pharmacokinetic considerations, toxicities, and treatment approaches for notable opioids are reviewed.

show abstract

Seizures in tramadol overdoses reported in the ToxIC registry: predisposing factors and the role of naloxone

Cited by 18 publications

References 48 publications

Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat

Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat

Acute Toxic Effects of the New Psychoactive Substance “Voodoo” among Patients presented to the Poison Control Center of Ain Shams University Hospitals (PCC-ASUH), Egypt, during 2017

Clinical Pharmacology, Toxicity, and Abuse Potential of Opioids

Contact Info

Product

Resources

About