Document Detail

4-aminopyridine toxicity: a case report and review of the literature.
MedLine Citation:
PMID:  22782458     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: 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.
CASE REPORT: 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.
DISCUSSION: 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.
Andrew M King; Nathan B Menke; Kenneth D Katz; Anthony F Pizon
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Publication Detail:
Type:  Case Reports; Journal Article; Review    
Journal Detail:
Title:  Journal of medical toxicology : official journal of the American College of Medical Toxicology     Volume:  8     ISSN:  1937-6995     ISO Abbreviation:  J Med Toxicol     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-20     Completed Date:  2013-02-12     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  101284598     Medline TA:  J Med Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  314-21     Citation Subset:  IM    
Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh Medical Center, PUH South Tower, Suite M2935, Pittsburgh, PA 15213, USA.
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MeSH Terms
4-Aminopyridine / blood,  poisoning*,  therapeutic use
Benzodiazepines / therapeutic use
Drug Overdose / diagnosis*,  drug therapy
Multiple Sclerosis / drug therapy
Paroxetine / therapeutic use
Propylene Glycols / therapeutic use
Sphingosine / analogs & derivatives,  therapeutic use
Reg. No./Substance:
0/Propylene Glycols; 123-78-4/Sphingosine; 12794-10-4/Benzodiazepines; 3QN8BYN5QF/fingolimod; 504-24-5/4-Aminopyridine; 61869-08-7/Paroxetine

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