Clinical toxicology : the official journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists
-
Clin Toxicol (Phila) · Jul 2015
ReviewCYP2D6 genetic polymorphisms and their relevance for poisoning due to amfetamines, opioid analgesics and antidepressants.
Cytochrome P450 2D6 (CYP2D6) is a member of the cytochrome P450 (CYP) superfamily involved in the biotransformation of drugs and substances of abuse encountered in clinical toxicology. Among the CYP superfamily, the CYP2D6 gene is considered as the most polymorphic as more than 105 different alleles have been identified so far. CYP2D6 genetic polymorphisms have the potential to affect the toxicity of their substrates. ⋯ Either poor or extensive/ultra-rapid CYP2D6 metabolisers may be exposed to toxic effects of amfetamines, opioid analgesics and antidepressants. In these three categories, the level of evidence is substance dependent, with differences within the same pharmacological class.
-
Clin Toxicol (Phila) · Jul 2015
Observational StudyTramadol overdose causes seizures and respiratory depression but serotonin toxicity appears unlikely.
Tramadol is a commonly used centrally acting analgesic associated with seizures and suspected to cause serotonin toxicity in overdose. ⋯ Tramadol overdose is associated with seizures and respiratory depression, but is unlikely to cause serotonin toxicity.
-
Clin Toxicol (Phila) · Jul 2015
Case ReportsCardiac sodium channel blockade after an intentional ingestion of lacosamide, cyclobenzaprine, and levetiracetam: Case report.
Lacosamide treats partial seizures by enhancing slow inactivation of voltage-gated sodium channels. The described cardiac toxicity of lacosamide in the literature to date includes atrioventricular blockade (PR prolongation), atrial flutter, atrial fibrillation, sinus pauses, ventricular tachycardia and a single cardiac arrest. We report a second case of cardiac arrest following an intentional lacosamide overdose. ⋯ The patient's lacosamide, cyclobenzaprine and levetiracetam overdose was associated with QRS prolongation and terminal right axis deviation--suggesting sodium channel blockade as a likely etiology for her cardiac arrest. Cyclobenzaprine has potential for sodium channel blockade and ventricular dysrhythmias although cardiac toxicity due to cyclobenzaprine alone is rare. The combination of cyclobenzaprine with lacosamide may have resulted in cardiovascular collapse. In conclusion, overdose of lacosamide combined with therapeutic concentrations of sodium channel blocking xenobiotics may cause cardiac conduction delays and cardiac arrest.
-
Clin Toxicol (Phila) · Jul 2015
Case ReportsMixed amlodipine/valsartan overdose treated by the molecular adsorbent recirculating system (MARS™).
We describe the case of a 58-year-old woman who developed a severe distributive shock following the intentional ingestion of a large overdose of amlodipine (480 mg) combined with valsartan (3680 mg). Extreme vasoplegia remained refractory to maximal standard therapy including fluid resuscitation, intravenous calcium, vasopressors at very high doses, hyperinsulinemia-euglycemia therapy, lipid emulsion, and methylene blue administration. Besides, the patient exhibited hyperglycemia refractory to very high doses of insulin. Due to its theoretical ability to effectively remove protein-bound drugs such as amlodipine from the circulation, albumin dialysis with the molecular adsorbent recirculating system (MARS™) was performed during two consecutive sessions. Blood was drawn for toxicokinetic calculations. Amlodipine elimination half-life during the first MARS™ session was calculated at 7.6 h. In addition, there was a rapid fall in blood glucose, requiring the introduction of a continuous infusion of glucose in order to achieve euglycemia. Moreover, a few hours after the initiation of the MARS™ therapy, the hemodynamic status was not significantly modified but a significant tapering of epinephrine infusion was possible, together with a progressive decrease of blood lactate level. However, the need for vasopressors in decreasing doses was present until day 5 post-ingestion. Eventually, the patient fully recovered and was discharged home 8 days after admission. ⋯ The role of the MARS™ in the treatment of severe poisoning of calcium channel blockers is still to be defined. We were able to demonstrate a relatively short elimination half-life of amlodipine. A decreased insulin resistance and a reduction of epinephrine infusion were also observed.
-
Drug shortages have significantly increased over the past decade. There are limited data describing how shortages impact medical toxicology of drugs. ⋯ Drug shortages affected a substantial number of critical agents used in the management of poisoned patients. Shortages were often of long duration and for drugs without alternatives. Providers caring for poisoned patients should be aware of current shortages and implement mitigation strategies to safeguard patient care.