RT Book, Section
A1 Kearney, Thomas E.
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.
SR Print(0)
ID 1179992850
T1 ANTIPSYCHOTIC DRUGS (HALOPERIDOL, DROPERIDOL, OLANZAPINE, AND ZIPRASIDONE)
T2 Poisoning & Drug Overdose, 7e
YR 2018
FD 2018
PB McGraw-Hill Education
PP New York, NY
SN 9780071839792
LK accessmedicine.mhmedical.com/content.aspx?aid=1179992850
RD 2024/04/25
AB PharmacologyHaloperidol  and  droperidol  are  butyrophenone  neuroleptic  drugs,  often  referred  to  as  "first-generation"  or  "typical"  antipsychotics,  that  are  useful  for  the  management  of  acutely  agitated  psychotic  patients  and  as  antiemetics.  They  have  strong  central  antidopaminergic  activity  and  weak  anticholinergic  and  anti-alpha-adrenergic  effects.Olanzapine  and  ziprasidone  are  second-generation  or  "atypical"  antipsychotic  agents.  They  have  weaker  and  more  selective  antidopaminergic  activity  and  a  higher  ratio  of  serotonin-to-dopamine  antagonism.  This  provides  less  risk  for  extrapyramidal  side  effects.  However,  olanzapine  has  greater  anticholinergic  effects,  and  both  have  greater  antihistaminic  and  anti-alpha-adrenergic  effects.  Therefore,  they  have  a  greater  propensity  to  cause  sedation  and  orthostatic  hypotension.Pharmacokinetics.  Haloperidol  is  well  absorbed  from  the  GI  tract  and  by  the  intramuscular  route.  Droperidol  is  available  only  for  parenteral  use  and  is  also  well  absorbed  by  the  intramuscular  route.  Droperidol  has  a  more  predictable  and  rapid  onset  of  3–10  minutes,  and  both  have  peak  pharmacologic  effects  that  occur  within  30–40  minutes  of  an  intramuscular  injection.  Both  drugs  are  metabolized  principally  by  the  liver.  The  serum  half-life  for  haloperidol  is  12–24  hours.  Olanzapine  and  ziprasidone  are  well  absorbed  from  the  GI  tract  and  by  the  intramuscular  route.  Olanzapine  IM  results  in  rapid  absorption,  with  peak  levels  occurring  within  15–45  minutes,  whereas  ziprasidone  IM  has  peak  levels  occurring  at  approximately  30–60  minutes.  Both  drugs  are  metabolized  principally  by  the  liver.  The  serum  half-life  for  olanzapine  is  20–54  hours,  and  for  ziprasidone,  it  is  2–5  hours.IndicationsHaloperidol  is  used  for  the  management  of  acute  agitated  functional  psychosis  or  extreme  agitation  induced  by  stimulants  or  hallucinogenic  drugs,  especially  when  drug-induced  agitation  has  not  responded  to  a  benzodiazepine.Droperidol  has  a  more  rapid  onset  and  greater  efficacy  for  agitation  and  is  also  useful  for  drug-  or  toxin-induced  nausea  and  vomiting,  but  its  role  in  routine  therapy  is  uncertain  because  of  reports  of  deaths  and  a  "black  box"  warning  about  QT  prolongation  (see  Item  IV.  D  below).  Therefore,  other  antiemetic  drugs  (eg,  metoclopramide  and  ondansetron)  should  be  considered  as  first-line  drugs  to  control  persistent  nausea  and  vomiting.Olanzapine  and  ziprasidone  by  the  intramuscular  (IM)  route  are  approved  for  the  management  of  acute  agitation  associated  with  schizophrenia,  in  addition  to  bipolar  mania  for  olanzapine.  Both  have  been  used  for  the  management  of  acute  undifferentiated  agitation  of  either  psychiatric  or  organic  (eg,  drug-induced)  origin.  They  may  have  comparable  efficacy  to  haloperidol  when  administered  by  the  IM  route  to  treat  acute  agitation.Note:  Benzodiazepines  are  the  usual  first-line  therapy  for  stimulant  (eg,  cocaine  or  amphetamine)  intoxications  and  alcohol  withdrawal  syndromes.  Combining  an  antipsychotic  with  a  benzodiazepine  may  shorten  the  time  to  sedation  for  the  treatment  of  acute  agitation.Nonbenzodiazepine  sedatives  (either  propofol  or  dexmedetomidine)  are  often  the  preferred  agents  for  sedation  in  mechanically  ventilated  adult  ICU  patients.ContraindicationsSevere  CNS  depression  in  the  absence  of  airway  and  ventilatory  control.Severe  parkinsonism.Known  hypersensitivity  to  the  individual  agent.  Droperidol  is  structurally  similar  to  haloperidol.  Olanzapine  is  a  thienobenzodiazepine  and  similar  to  clozapine.  Ziprasidone  has  a  unique  chemical  structure,  a  benzisothiazolyl  piperazine.Prolonged  QTc  interval.  Before  droperidol  administration,  a  12-lead  ECG  is  recommended.Adverse  effectsHaloperidol  and  droperidol  produce  less  sedation  and  less  hypotension  than  the  atypical  ...