Diphenylhydantoin toxicity

Peters BH, SamaanNA H3(perglycaemia with relative hypoinsulinemia in diphenylhydantoin toxicity. NEnglJMed 969) 281, 91-2. 

Phenytoin. Phenytoin sodium is sodium diphenylhydantoin [630-93-3] which is stmcturally related to the barbiturates. It was originally introduced as an anticonvulsant (18) (see Hypnotics, sedatives, and anticonvulsants) and later found to have antiarrhythmic properties (19), although not approved by the PDA for any arrhythmic indications. Phenytoin is effective in the treatment of ventricular arrhythmias associated with acute MI and with digitalis toxicity (20). It is not very effective in treatment of supraventricular arrhythmias (20). 

Review of the literature regarding toxic effects of mirex and chlordecone did not reveal any human populations that are known to be unusually sensitive to mirex or chlordecone. However, based on knowledge of the toxicities of mirex and chlordecone, some populations can be identified that may demonstrate unusual sensitivity to these chemicals. Those with potentially high sensitivity to mirex include the very young. Those with potentially high sensitivity to chlordecone include juvenile and elderly person and persons being treated with some antidepressants or the anticonvulsant, diphenylhydantoin. 

Tilson HA, Hong JS, Mactutus CF. 1985. Effects of 5,5-diphenylhydantoin (phenytoin) on neurobehavioral toxicity of organochlorine insecticides and permethrin. J Pharmacol Exp Ther... 

K22. Kutt, H., Winters, W., Kokenge, R., and McDowell, F., Diphenylhydantoin metabolism, blood levels ana toxicity. Arch. Neurol. 11, 642-648 (1964). 

As with the digitalis glycosides, the toxic effects of the anticonvulsant drug diphenylhydantoin result from elevated plasma levels of the drug. This can simply be due to inappropriate dosage, but other factors may also be involved in the development of toxicity. 

Another cause of toxicity with diphenylhydantoin can be the result of interactions with other drugs such as isoniazid. This drug is a noncompetitive inhibitor of the aromatic hydroxylation of diphenylhydantoin. Consequently, the elimination of diphenylhydantoin is impaired in the presence of isoniazid, and the plasma level is greater than anticipated for a normal therapeutic dose. Furthermore, it was found that there was a significant correlation... 

This greater incidence in toxicity in slow acetylators corresponded with a greater increase in the plasma level of diphenylhydantoin when the drugs were taken in combination. This was due to higher plasma levels of isoniazid in slow acetylators, causing a greater degree of inhibition of diphenylhydantoin metabolism. 

Scleroderma Vinyl chloride T richloroethylene Spanish toxic oil Tryptophan Silicone Interleukin-2 Diphenylhydantoin... 

More recently it has become apparent that genetic factors also affect phase 1, oxidation pathways. Early reports of the defective metabolism of diphenylhydantoin in three families and of the defective deethylation of phenacetin in certain members of one family indicated a possible genetic component in microsomal enzyme-mediated reactions. Both these cases resulted in enhanced toxicity. Thus, diphenylhydantoin, a commonly used anticonvulsant, normally undergoes aromatic hydroxylation and the corresponding phenolic metabolite is excreted as a glucuronide (figure 7,35). Deficient... 

Phenytoin (diphenylhydantoin, Dilantin) has been in use as an antiepileptic agent since 1938. Its ability to abolish ventricular tachycardia was noted much later. It is currently used in the treatment of several clinical arrhythmic disorders but especially in disorders induced by toxic dosage levels of digitalis, in ventricular tachycardia, and in atrial tachycardia with block. It is probably not effective in other types of atrial arrhythmias. 

The potential therapeutic implications of relatively broad (phenobarbital-type) induction are obvious patients chronically treated with phenobarbital may require larger than normal doses of other drugs (diphenylhydantoin. bishydroxycoumarin) to achieve therapeutic effects. If the phenobarbital is discontinued, enzyme induction disappears and the large drug doses may precipitate toxicity. Similarly, chronic administration of a drug may induce microsomal enzymes that catalyse its own metabolism, i.e. produce auto-induction . Thus, repeated drug administration may... 

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