Lorazepam antidote1/23/2024 ![]() ![]() Physostigmine has been used for acetylcholinesterase inhibition, but it is not currently available. Benzodiazepines (e.g., lorazepam) for seizures or convulsions, sodium bicarbonate for ventricular arrhythmia, and VA-ECMO for hemodynamic support can be used for the management of the clinical manifestations of diphenhydramine toxicity. The mainstay of therapy for diphenhydramine toxicity is supportive management that addresses the symptomatology of intoxication/overdose. There is currently no antidote that specifically works to reverse the effects of diphenhydramine toxicity. Other decontamination procedures such as ipecac, cathartics, or gastric lavage have not been proven to be beneficial or routinely used due to a lack of demonstrated efficacy and increased risk of complications. However, the use of charcoal is avoided in patients with altered mental status unless the airway is protected. Single-dose activated charcoal may benefit, especially as anticholinergic effects may result in decreased gastrointestinal motility leading to delayed absorption of diphenhydramine. ![]() If the patient presents within 1 hour of ingestion of diphenhydramine, decontamination techniques may be considered. ![]() Serum creatinine, urine output, and creatine phosphokinase should be obtained to rule out rhabdomyolysis in the setting of seizure. Furthermore, despite undergoing extensive hepatic metabolism, diphenhydramine is not expected to cause any abnormal elevations in liver function tests or be linked to liver injury. An acetaminophen level should also be obtained to either confirm or rule out acetaminophen as a coingestant.ĭiphenhydramine plasma levels do not provide any relevant clinical information and are also not readily available. An EKG should be obtained and assessed for any changes that may indicate the presence of any arrhythmias (e.g., torsades de pointes). Vital signs, including blood pressure, heart rate, respiratory rate, temperature, and oxygen saturation, should be obtained to aid in this initial assessment. Īn assessment utilizing the ABCDE (airway, breathing, circulation, disability, exposure) approach should be performed upon initial presentation to assess the severity of intoxication/overdose quickly. Furthermore, severe symptoms, characterized as delirium/psychosis, seizures, coma, and death, manifested at doses of 1 gram or more. One retrospective study observed that moderate symptoms, characterized as agitation, confusion, hallucinations, and ECG disturbances, occurred at doses of 0.3 grams. Studies have shown that diphenhydramine toxicity is dose-dependent. The drug undergoes metabolism to much smaller degrees in the pulmonary and renal system and is, thus, minimally removed by hemodialysis. Most of the diphenhydramine that is hepatically metabolized undergoes N-demethylation via CYP2D6, with minor demethylation occurring via CYP1A2, CYP2C9, AND CYP2C19. It is extensively metabolized by the liver via cytochrome P450 enzymes. For adult patients, the Vd is approximately 17 L/kg (range: 13 to 20 L/kg) and approximately 14 L/kg (range: 7 to 20 L/kg) for elderly patients. For pediatric patients, the Vd is approximately 22 L/kg (range: 15 to 28 L/kg). Diphenhydramine is lipophilic and has a relatively large volume of distribution (Vd). For adult patients, the elimination half-life is approximately 9 hours (range: 7 to 12 hours) and approximately 13.5 hours (range: 9 to 18 hours) for elderly patients (range: 9 to 18 hours). ![]() For pediatric patients, the elimination half-life is approximately 5 hours (range: 4 to 7 hours). The elimination half-life of diphenhydramine can vary between age groups. Peak serum levels of diphenhydramine are reached approximately 2 to 3 hours after oral administration. As a result, individuals are at increased risk of developing potentially fatal arrhythmias, such as torsade de pointes.ĭiphenhydramine pharmacokinetics do not appear to change in the event of intoxication/overdose. This leads to the prolongation of the QT interval and a flattening of the T-wave. These channels are responsible for the rapid component of the cardiac repolarizing current. More specifically, diphenhydramine can affect the delayed rectifier potassium ion channels of the heart as it can act as a blocker of potassium channels. ECG changes can be observed, which include the widening of the QRS-complex and tachycardia, possibly caused by the anticholinergic effects of diphenhydramine. Diphenhydramine can also have negative cardiovascular consequences in the setting of toxicity. ![]()
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