Introduction
The aminoketone family of antidepressant medication bupropion hydrochloride was first marketed in 1985. It has various off-label uses, including treating sexual dysfunction brought on by antidepressant usage, generalized anxiety disorder, ADHD (attention-deficit/hyperactivity disorder), and bipolar disorder. In addition, it is currently approved for treating major depressive disorder, seasonal affective disorder, and smoking cessation. There are numerous formulations, including extended-release (ER), sustained-release (SR), and immediate-release (IR).
Drug side effects at therapeutic doses are generally non-specific and can include weight loss, constipation, headaches, nausea, irritability, and dry mouth. Bupropion was taken off the market in 1986 when a tiny percentage of bulimic patients experienced new-onset seizures; nevertheless, it was brought back in 1989 at reduced dose ranges. Patients with a history of seizures, eating problems, or those going through alcoholic or CNS depressant withdrawal are now contraindicated from the medication. With doses up to 450 mg per day, the risk of seizures rises to 0.4 % from an estimated 0.1 % with doses below 300 mg per day.
A common side effect of overdose is agitation, tachycardia (increased heart rate), and convulsions. For up to 24 hours after consumption, the extended-release version has also been linked to delayed seizures. In addition, cardiogenic shock, life-threatening arrhythmias, and status epilepticus have all been documented in overdose cases.
What Is the Etiology of Bupropion Toxicity?
Bupropion is an aminoketone categorized as a norepinephrine-dopamine reuptake inhibitor. Seizures, including status epilepticus, are frequently observed in overdose cases, while the precise mechanism is unknown. Cardiovascular toxicity can arise in dysrhythmias, cardiogenic shock, or conduction delays that widen the QRS and QT intervals (measurement of electric properties of the heart). Notably, QRS lengthening is associated with myocardial gap junctions and interruption of intercellular communication rather than the heart sodium channel.
What Is the Epidemiology of Bupropion Toxicity?
Given that they are prescribed to those with depression, antidepressants are commonly linked to overdose. Due to the drug's structural resemblance to amphetamines, purposeful misuse of Bupropion has also been documented. This includes abuse through insufflation. About 16,126 overdoses of Bupropion were reported by one association in 2020. Only roughly half of these exposures, which included eight fatalities, were single exposures.
What Are the Symptoms of Bupropion Toxicity?
Any potential exposure should be the subject of a complete medical history and physical examination, supporting later judgments. It is important to determine when and how much food was consumed. The clinician should assess co-ingestions. It is important to determine why someone overdosed. The review of medications should be included in the history to spot any interactions that could cause seizures or cardiovascular collapse.
Inconsistent physical exam results include tachycardia, convulsions, and agitation, the most often reported overdose symptoms. In retrospective investigations, the frequency of seizures ranges from 17 % to 47 %. Hypertension (increased blood pressure), psychosis patient losing contact with reality), hyperreflexia (overresponsive reflexes), clonus (rhythmic and uncontrollable muscular contractions caused by damage to descending motor neurons), central nervous system depression, numbness, and dystonia (involuntary contraction of muscles) are other symptoms.
What Is the Treatment Given for Bupropion Toxicity?
Since there is no specific antidote for Bupropion overdose, supportive care is the main management strategy. A local poison control center or toxicologist consultation may be beneficial, particularly in extreme circumstances involving major organ-system malfunction. Patients who appear shortly after a significant overdose and do not require airway protection may benefit from decontamination with activated charcoal. Unintentional overdose rarely results in clinically significant effects. However, severe adverse responses (seizures) have been documented even after ingesting two doses.
Seizures should be treated with Benzodiazepines as first-line agents and Barbiturates, such as Phenobarbital, as second-line agents. Avoidance of other anti-epileptics, including Phenytoin, is recommended, given possible drug-to-drug interactions. Depending on the clinical situation, life-threatening arrhythmias should be treated. Widened QRS complex on the electrocardiogram often suggests fast sodium channel blockade. Therefore, in the wide QRS with hemodynamic instability or dysrhythmias, boluses of sodium bicarbonate are typically given to the patient. Unfortunately, Bupropion-induced QRS prolongation may not respond to sodium bicarbonate since the cardiotoxicity does not appear to be due to fast sodium channelopathy and results from impaired gap junction communication.
Vasopressors should be used as the first line of treatment for cardiogenic shock. The year 2016 saw the endorsement of intravenous lipid emulsion (ILE) by a clinical toxicology task group for severe life-threatening toxicity, such as refractory status epilepticus or hemodynamic instability. The task group recommended first-line modalities such as Benzodiazepines and Phenobarbital as conventional therapies for seizures. ILE was not advised for pulseless electrical activity since it might conflict with extracorporeal and epinephrine therapies.
In the case of reports, ILE has been demonstrated to improve hemodynamic state quickly and left ventricular ejection fraction in overdose cases. Therefore, ILE is typically employed as a last resort, although some instances might support an earlier start. In addition, veno-arterial extracorporeal membrane oxygenation can treat refractory cardiogenic shock and cardiopulmonary arrest.
In an ICU setting, patients who have seizures, hemodynamic instability, or life-threatening arrhythmias should be closely watched. All overdoses of Bupropion, even therapeutic mistakes, should be monitored for delayed-onset seizures for 24 hours. At discharge, patients should be symptom-free.
What Is the Differential Diagnosis of Bupropion Toxicity?
It is important to assess each ingestion for any potential co-ingestions. In addition, a differential of the factors causing sympathomimetic, anticholinergic, and serotonin syndromes should be considered, given that Bupropion has been linked to these disorders.
What Are the Complications Associated With Bupropion Toxicity?
Possible complications of Bupropion toxicity include the following:
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Status epilepticus.
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Severe mental impairment combined with a breach in airway protection.
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Cardiovascular shock.
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Potentially fatal dysrhythmias.
How to Enhance Healthcare Outcomes of Bupropion Toxicity?
When a patient exhibits symptoms of Bupropion poisoning, the medical staff must assess and manage the patient immediately. This team includes the emergency room doctor, toxicology or poison, and critical care team. These teams' coordinated efforts can effectively screen patients and manage them as needed. Patients should have the following when they enter the emergency room:
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Recorded vital signs.
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Electrocardiogram.
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A local poison control center should be consulted for advice and epidemiology.
For assistance with clinical management, a toxicologist should be consulted. Bupropion toxicity in patients necessitates surveillance. After receiving medical clearance, intentional overdoses call for a mental examination. In addition, risk reduction techniques should be used to handle unintentional overdoses, including patient education, keeping drugs in a secure area, and making sure patients can manage their medications.
Conclusion
The main purpose of the drug Bupropion is to treat serious depressive illness. It is a norepinephrine-dopamine reuptake inhibitor that is an aminoketone. This medicine can cause toxicity to the heart and brain when taken in excess, resulting in dysthymias and several other complications.
