Treatment of drug‐induced seizures

Abstract

Seizures are a common complication of drug intoxication, and up to 9% of status epilepticus cases are caused by a drug or poison. While the specific drugs associated with drug‐induced seizures may vary by geography and change over time, common reported causes include antidepressants, stimulants and antihistamines. Seizures occur generally as a result of inadequate inhibitory influences (e.g., gamma aminobutyric acid, GABA) or excessive excitatory stimulation (e.g. glutamate) although many other neurotransmitters play a role. Most drug‐induced seizures are self‐limited. However, status epilepticus occurs in up to 10% of cases. Prolonged or recurrent seizures can lead to serious complications and require vigorous supportive care and anticonvulsant drugs. Benzodiazepines are generally accepted as the first line anticonvulsant therapy for drug‐induced seizures. If benzodiazepines fail to halt seizures promptly, second line drugs include barbiturates and propofol. If isoniazid poisoning is a possibility, pyridoxine is given. Continuous infusion of one or more anticonvulsants may be required in refractory status epilepticus. There is no role for phenytoin in the treatment of drug‐induced seizures. The potential role of ketamine and levetiracetam is promising but not established.

Propofol Use for Toxin‐Related Seizures

“…Despite a paucity of published data, propofol is being used in the management of toxin‐related seizures caused by a wide variety of substances. The use of propofol has been advocated rarely by previous authors, and only recently has this been addressed in an article based on published clinical evidence . One study classifies propofol as a second‐line anticonvulsant in the treatment of drug‐induced seizures and cites its efficacy in poisonings with amoxapine and star fruit.…”

“…The use of propofol has been advocated rarely by previous authors, 4 and only recently has this been addressed in an article based on published clinical evidence. 5 One study classifies propofol as a second-line anticonvulsant in the treatment of drug-induced seizures and cites its efficacy in poisonings with amoxapine and star fruit. Additional case reports involving strychnine, amitriptyline, venlafaxine, severe ethanol withdrawal, and diphenhydramine all describe the successful use of propofol as an adjunct in the treatment of toxin-induced seizures.…”

Case Files of the University of California, San Francisco Medical Toxicology Fellowship: Seizures and a Persistent Anion Gap Metabolic Acidosis

“…There is no single mechanism that explains all causes of drug-induced seizures; however, there are several common pathways that may help focus the differential diagnosis. Seizures may occur as the result of a loss of the normal inhibitory pathways [1], or conversely, enhancement of excitatory pathways. Gamma-aminobutyric acid (GABA) is the primary neurotransmitter responsible for maintaining inhibitory tone in the central nervous system.…”

“…Conversely, the accumulation of excitatory neurotransmitters can also result in seizures. Examples include the accumulation of catecholamines such as norepinephrine and dopamine as seen in cocaine use [1], or the accumulation of monoamines such as serotonin following selective serotonin reuptake inhibitor (SSRI) ingestions [1]. Finally, adenosine receptor blockade following methylxanthine ingestion results in increased glutamate release, an important excitatory neurotransmitter, resulting in a decrease in the seizure threshold [1].…”

“…The loss of chronic inhibition of GABA receptors in the central nervous system coupled with the upregulation of NMDA receptors, as is seen in alcohol and benzodiazepine withdrawal, is a common mechanism resulting seizures [1]. Finally, toxins causing cellular hypoxia such as cyanide result in seizures.…”