Toxicity to the nervous system of diphenylhydantoin: a review
Ziegler, D.K.
International Journal of Neurology 11(4): 383-400
1978
ISSN/ISBN: 0020-7446 PMID: 94596 Document Number: 3665
Diphenylhydantoin may have direct toxic action on the central or peripheral nervous system. Temporary cerebellar dysfunction is the commonest clinical sign, and can rarely be permanent. In massive doses DPH causes, in addition, agitated, semistuporous states often with various acute psychotic manifestations. Seizures may be precipitated. Depression of vital functions is rare and stimulants should not be used. Long-term DPH administration on occasion can give impairment of peripheral nerve function. Nervous system function can be adversely affected indirectly by DPH toxicity through three mechanisms: (1) Production of peripheral neuropathy on myelopathy with anemia secondary to DPH effect con f olate metabolism; (2) shock or cardiac arrhythmia induced by intravenous DPH; (3) production of hyperglycemia nonketotic coma produced by DPH intoxication. Neurotoxicity of DPH is accompanied by abnormal EEG patterns; these usually consist of slow activity but various seizure patterns can also occur. DPH can alter cerebrospinal fluid protein, protein bound iodine plasma and urinary corticosteroids. These findings probably have no clinical significance. Afairly good correlation exists between DPH serum levels and degree of neurotoxicity although many cases with high DPH levels are free of clinical signs of toxicity. Only a rough correlation exists between dosage regimen and serum DPH levels maintained. It is known that in some patients concomitant administration of INH or Dicoumarol will slow metabolism of DPH.
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