Tizanidine hydrochloride is a centrally acting imidazoline derivative with α-2 adrenoreceptor agonist properties. Physiologically, tizanidine activates presynaptic α-2 adrenoreceptors within the central nervous system thereby inhibiting the release of excitatory neurotransmitter norepinephrine via negative feedback mechanism7.
Common side effects of tizanidine include somnolence, dry mouth, asthenia, and dizziness. Reports of overdose often describe hypotension and bradycardia1,4. Currently, there is no known antidote for tizanidine intoxication and treatment options are limited to endotracheal intubation as well as administration of intravenous fluids and vasopressors as necessary5,6.
Central α-2 receptor agonists toxicity has been well-documented in numerous case series and case reports8,9, with effects ranging from central nervous system depression, bradycardia, hypotension, miosis, and hypothermia. They have also been suggested as a “one pill can kill” drug when adult doses are unintentionally ingested by children10.
Retrospective investigations of unintentional pediatric exposures to central α-2 receptor agonists have indicated a significant increase of tizanidine intoxication over an 11-year period8. Treatment of these exposures varied between atropine, IV fluids, naloxone, and vasopressors, illustrating that one specific therapy was not highly effective.
Acute intoxication with central α-2 receptor agonists presents a recognizable clinical entity with signs and symptoms that largely resemble opiate intoxication, prompting the use naloxone hydrochloride as a reversal agent for this type of poisoning. The therapeutic mechanism of naloxone is thought to work by competing with endogenous opioids leading to an increase in sympathetic tone5.
There have been multiple case reports over the past decades describing naloxone as a viable agent for acute α-2 receptor agonists toxicity. For example, a single 0.1 mg dose of naloxone was described to resolve tetrahydrozoline toxicity in a 36-month-old toddler within 30 seconds of administration11. A similar case also described one-time 0.1 mg dose of naloxone resolved symptoms of tetrahydrozoline toxicity in a 25-day-old infant12.
Successful naloxone therapy was also documented in unintentional pediatric clonidine and guanfacine exposures13–15. However, it should be noted that the use of naloxone remains controversial with multiple reports describing inefficacy7,16.
Despite the abundant documentation regarding the use of naloxone for pediatric clonidine, brimonidine, guanfacine and tetrahydrozoline poisonings, there are limited reports for its use in pediatric tizanidine poisoning. To such effect, this case report provides additional epidemiologic data on childhood tizanidine poisoning and further documentation on the use of naloxone as a viable antidote for centrally acting α-2 receptor agonists.