4-aminopyridine toxicity: a case report and review of the literature.
BACKGROUND
4-Aminopyridine (4-AP) selectively blocks voltage-gated potassium channels, prolongs the action potential, increases calcium influx, and subsequently, enhances interneuronal and neuromuscular synaptic transmission. This medication has been studied and used in many disease processes hallmarked by poor neuronal transmission in both the central and peripheral nervous systems including: multiple sclerosis (MS), spinal cord injuries (SCI), botulism, Lambert-Eaton syndrome, and myasthenia gravis. It has also been postulated as a potential treatment of verapamil toxicity and reversal agent for anesthesia-induced neuromuscular blockade. To date, there have been limited reports of either intentional or accidental 4-AP toxicity in humans. Both a case of a patient with 4-AP toxicity and review of the literature are discussed, highlighting commonalities observed in overdose.


METHODS
A 37-year-old man with progressive MS presented with diaphoresis, delirium, agitation, and choreathetoid movements after a presumed 4-AP overdose. 4-AP concentration at 6 h was 140 ng/mL. With aggressive benzodiazepine administration and intubation, he recovered uneventfully.


CONCLUSIONS
The commonalities associated with 4-AP toxicity conforms to what is known about its mechanism of action combining cholinergic features including diaphoresis, altered mental status, and seizures with dopamine-related movement abnormalities including tremor, choreoathetosis, and dystonia. Management of patients poisoned by 4-AP centers around good supportive care with definitive airway management and controlling CNS hyperexcitability aggressively with gamma-aminobutyric acid agonist agents. Adjunctive use of dopamine antagonists for extrapyramidal effects after sedation is a treatment possibility. As 4-aminopyridine recently received Federal Drug Administration approval for the treatment of ambulation in patients with MS, physicians should be keenly aware of its presentation, mechanism of action, and management in overdose.
Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh Medical Center, PUH South Tower, Suite M2935, Pittsburgh, PA 15213, USA. kingam@upmc.edu
Andrew M
AM
King
Nathan B
NB
Menke
Kenneth D
KD
Katz
Anthony F
AF
Pizon
D015761:4-Aminopyridine / Q000097:blood / Q000506:poisoning* / Q000627:therapeutic use; D000328:Adult; D001569:Benzodiazepines / Q000627:therapeutic use; D062787:Drug Overdose / Q000175:diagnosis* / Q000188:drug therapy; D000068876:Fingolimod Hydrochloride; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy; D017374:Paroxetine / Q000627:therapeutic use; D011409:Propylene Glycols / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives / Q000627:therapeutic use
D011409:Propylene Glycols; D001569:Benzodiazepines; D017374:Paroxetine; D015761:4-Aminopyridine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine