2770 T3D2728 Phenytoin An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. 57-41-0 1775 C15H12N2O2 252.089880 White powder. 286°C 32 mg/L (at 22°C) Intravenous, Oral, Intramuscular. Bioavailability 70-100% oral, 24.4% for rectal and intravenous administration. Rapid rate of absorption with peak blood concentration expected in 1&frac12; to 3 hours. Phenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Primarily hepatic. The majority of the dose (up to 90%) is metabolized to 5-(4'-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). This metabolite undergoes further glucuronidation and is excreted into the urine. CYP2C19 and CYP2C9 catalyze the aforementioned reaction. Route of Elimination: Most of the drug is excreted in the bile as inactive metabolites which are then reabsorbed from the intestinal tract and excreted in the urine. Urinary excretion of phenytoin and its metabolites occurs partly with glomerular filtration but, more importantly, by tubular secretion. Half Life: 22 hours (range of 7 to 42 hours) Oral, mouse: LD<sub>50</sub> = 150 mg/kg; Oral, rat: LD<sub>50</sub> = 1635 mg/kg. 2B, possibly carcinogenic to humans. (L135) For the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. Symptoms of overdose include coma, difficulty in pronouncing words correctly, involuntary eye movement, lack of muscle coordination, low blood pressure, nausea, sluggishness, slurred speech, tremors, and vomiting. Treatment is nonspecific since there is no known antidote. The adequacy of the respiratory and circulatory systems should be carefully observed and appropriate supportive measures employed. Hemodialysis can be considered since phenytoin is not completely bound to plasma proteins. Total exchange transfusion has been used in the treatment of severe intoxication in pediatric patients. (L1712) 2009-07-21T20:26:24Z 2026-03-31T18:53:50Z Phenytoin C07443 8107 Phenytoin DB00252 549 true O=C1NC(=O)C(N1)(C1=CC=CC=C1)C1=CC=CC=C1 C15H12N2O2 InChI=1S/C15H12N2O2/c18-13-15(17-14(19)16-13,11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10H,(H2,16,17,18,19) CXOFVDLJLONNDW-UHFFFAOYSA-N 252.268 252.089877638 Exogenous Solid 2.47 HMDB14397 CHEMBL16 1710 <p>Mahdi B. Fawzi, Anne K. Taylor, &#8220;Parenteral phenytoin preparations.&#8221; U.S. Patent US4642316, issued April, 1981.</p> CHEM002154 DTXSID8020541 5,5-diphenylimidazolidine-2,4-dione