TY  - CHAP
M1  - Book, Section
TI  - PHENYTOIN AND FOSPHENYTOIN
A1  - Lewis, Justin C.
A2  - Olson, Kent R.
A2  - Anderson, Ilene B.
A2  - Benowitz, Neal L.
A2  - Blanc, Paul D.
A2  - Clark, Richard F.
A2  - Kearney, Thomas E.
A2  - Kim-Katz, Susan Y.
A2  - Wu, Alan H. B.
Y1  - 2018
N1  - 
T2  - Poisoning & Drug Overdose, 7e
AB  - Pharmacology.  The  neuronal  membrane-stabilizing  actions  of  phenytoin  through  sodium  channel  blockade  make  this  drug  popular  for  sustained  control  of  acute  and  chronic  seizure  disorders  and  useful  for  certain  cardiac  arrhythmias.  Because  of  the  relatively  slow  onset  of  anticonvulsant  action,  phenytoin  usually  is  administered  after  diazepam.  At  serum  concentrations  considered  therapeutic  for  seizure  control,  phenytoin  acts  similarly  to  lidocaine  to  reduce  ventricular  premature  depolarization  and  suppress  ventricular  tachycardia.  After  intravenous  administration,  peak  therapeutic  effects  are  attained  within  1  hour.  The  therapeutic  serum  concentration  for  seizure  control  is  10–20  mg/L.  Elimination  is  nonlinear,  with  an  apparent  half-life  averaging  22  hours.  Fosphenytoin,  a  prodrug  of  phenytoin  for  intravenous  use,  is  converted  to  phenytoin  after  injection,  with  a  conversion  half-life  of  8–32  minutes.IndicationsControl  of  generalized  tonic-clonic  seizures  or  status  epilepticus.  However,  benzodiazepines  and  phenobarbital  are  more  effective  for  treating  drug-induced  seizures.Control  of  cardiac  arrhythmias,  particularly  those  associated  with  digitalis  intoxication.Contraindications.  Known  hypersensitivity  to  phenytoin  or  other  hydantoins.Adverse  effectsRapid  intravenous  administration  of  phenytoin  (>50  mg/min  in  adults  or  1  mg/kg/min  in  children)  may  produce  hypotension,  AV  block,  and  cardiovascular  collapse,  probably  owing  to  the  propylene  glycol  diluent.  Fosphenytoin  is  readily  soluble  and  does  not  contain  propylene  glycol,  and,  therefore,  a  hypotensive  response  is  not  expected.  However,  a  few  cases  of  bradycardia  and  asystole  have  been  reported  after  very  large  IV  doses  of  fosphenytoin.Extravasation  of  phenytoin  may  result  in  local  tissue  necrosis  and  sloughing.  Phenytoin  may  induce  the  "purple  glove"  syndrome  (edema,  discoloration,  and  pain)  after  peripheral  IV  administration.  This  can  occur  hours  after  infusion,  in  the  absence  of  clinical  signs  of  extravasation,  and  can  lead  to  limb  ischemia  and  necrosis  from  a  compartment  syndrome.  Elderly  patients  receiving  large  multiple  doses  are  at  risk;  other  risk  factors  include  use  of  small  IV  catheters,  high  infusion  rates,  and  use  of  the  same  catheter  site  for  two  or  more  IV  push  doses.  Extravasation  problems  have  not  been  observed  with  fosphenytoin.Drowsiness,  ataxia,  nystagmus,  and  nausea  may  occur.Use  in  pregnancy.  FDA  category  D.  Congenital  malformations  (fetal  hydantoin  syndrome)  and  hemorrhagic  disease  of  the  newborn  have  occurred  with  chronic  use.  However,  this  does  not  preclude  acute,  short-term  use  in  a  seriously  symptomatic  patient  (Introduction).Drug  or  laboratory  interactionsThe  various  drug  interactions  associated  with  chronic  phenytoin  dosing  (ie,  accelerated  metabolism  of  other  drugs)  are  not  applicable  to  its  acute  emergency  use.Extracorporeal  removal  methods  (eg,  hemoperfusion  and  repeat-dose  activated  charcoal)  will  enhance  phenytoin  clearance.  Supplemental  dosing  may  be  required  during  such  procedures  to  maintain  therapeutic  levels.Dosage  and  method  of  administrationParenteralPhenytoin.  Administer  a  loading  dose  of  15–20  mg/kg  IV  slowly  at  a  rate  not  to  exceed  50  mg/min.Highly  sensitive  patients  (elderly,  patients  with  preexisting  cardiovascular  conditions)  should  receive  phenytoin  more  slowly  (20  mg/min),  and  children  at  1  mg/kg/min.Phenytoin  may  be  diluted  in  50–150  mL  of  normal  saline  with  the  use  of  an  in-line  0.22-0.5  micron  filter.  Further  dilution  to  5  mg/mL  may  help  reduce  the  risk  of  purple  glove  syndrome.Phenytoin  has  been  administered  via  the  intraosseous  route  in  children.  Do  not  administer  by  the  intramuscular  route.Fosphenytoin.  Dose  is  based  on  the  phenytoin  equivalent:  750  mg  of  fosphenytoin  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - accessmedicine.mhmedical.com/content.aspx?aid=1174607539
ER  -