TY  - CHAP
M1  - Book, Section
TI  - PHYSOSTIGMINE AND NEOSTIGMINE
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.
Y1  - 2018
N1  - 
T2  - Poisoning & Drug Overdose, 7e
AB  - Pharmacology.  Physostigmine  and  neostigmine  are  carbamates  and  reversible  inhibitors  of  acetylcholinesterase,  the  enzyme  that  degrades  acetylcholine.  They  increase  concentrations  of  acetylcholine,  causing  stimulation  of  both  muscarinic  and  nicotinic  receptors.  Physostigmine  may  also  have  a  direct  action  on  the  acetylcholine  receptor.  The  tertiary  amine  structure  of  physostigmine  allows  it  to  penetrate  the  blood-brain  barrier  and  exert  central  cholinergic  effects  as  well.  Neostigmine,  a  quaternary  ammonium  compound,  is  unable  to  penetrate  the  CNS.  Owing  to  cholinergic  stimulation  of  the  reticular  activating  system  of  the  brainstem,  physostigmine  has  nonspecific  analeptic  (arousal)  effects.  After  parenteral  administration  of  physostigmine,  the  onset  of  action  is  within  3–8  minutes  and  the  duration  of  effect  is  usually  30–90  minutes.  The  average  elimination  half-life  is  22  minutes  (range  12-40).  Neostigmine  has  a  slower  onset  of  7–11  minutes  and  a  longer  duration  of  effect  of  60–120  minutes.IndicationsPhysostigmine  is  used  for  the  management  of  severe  anticholinergic  syndrome  (agitated  delirium,  urinary  retention,  severe  sinus  tachycardia,  or  hyperthermia  with  absent  sweating)  from  antimuscarinic  agents  (eg,  benztropine,  atropine,  jimson  weed  [Datura],  diphenhydramine).  The  typical  indication  is  for  reversal  of  agitated  delirium  in  patients  requiring  physical  and/or  chemical  restraints.  For  a  discussion  of  anticholinergic  toxicity,  see  Anticholinergics.  Although  there  are  anecdotal  case  reports  of  the  use  of  physostigmine  to  treat  delirium  and  coma  associated  with  gamma-hydroxybutyrate  (GHB),  baclofen,  and  several  atypical  antipsychotic  (olanzapine,  clozapine,  quetiapine)  agents,  its  safety  and  efficacy  are  uncertain  with  these  intoxications.Physostigmine  is  sometimes  used  diagnostically  to  differentiate  functional  psychosis  from  anticholinergic  delirium.Neostigmine  is  used  primarily  to  reverse  the  effect  of  nondepolarizing  neuromuscular  blocking  agents.ContraindicationsSerious  tricyclic  antidepressant  overdose.  Physostigmine  may  worsen  cardiac  conduction  disturbances,  cause  bradyarrhythmias  or  asystole,  and  aggravate  or  precipitate  seizures.Do  not  use  physostigmine  concurrently  with  depolarizing  neuromuscular  blockers  (eg,  succinylcholine).Known  hypersensitivity  to  agent  or  preservative  (eg,  benzyl  alcohol,  bisulfite).Relative  contraindications  may  include  bronchospastic  disease  or  asthma,  peripheral  vascular  disease,  intestinal  and  bladder  blockade,  parkinsonian  syndrome,  and  cardiac  conduction  defects  (AV  block).Adverse  effectsBradycardia,  heart  block,  and  asystole.Seizures  (particularly  with  rapid  administration  or  excessive  dose  of  physostigmine).Nausea,  vomiting,  hypersalivation,  and  diarrhea.Bronchorrhea  and  bronchospasm  (caution  required  in  patients  with  asthma).Fasciculations  and  muscle  weakness.Use  in  pregnancy.  FDA  Category  C  (Introduction).  Transient  weakness  has  been  noted  in  neonates  whose  mothers  were  treated  with  physostigmine  for  myasthenia  gravis.Drug  or  laboratory  interactionsMay  potentiate  agents  metabolized  by  the  cholinesterase  enzyme  (eg,  depolarizing  neuromuscular  blocking  agents—succinylcholine,  cocaine,  esmolol),  cholinesterase  inhibitors  (eg,  organophosphate  and  carbamate  insecticides),  and  other  cholinergic  agents  (eg,  pilocarpine).They  may  inhibit  or  reverse  the  actions  of  nondepolarizing  neuromuscular  blocking  agents  (eg,  pancuronium,  vecuronium).  Neostigmine  is  used  therapeutically  for  this  purpose.They  may  have  additive  depressant  effects  on  cardiac  conduction  in  patients  with  cyclic  antidepressant,  beta-adrenergic  antagonist,  or  calcium  antagonist  overdoses.Physostigmine,  through  its  nonspecific  analeptic  effects,  may  induce  arousal  in  patients  with  GHB,  opioid,  benzodiazepine,  or  sedative-hypnotic  intoxication,  or  with  ketamine-  or  propofol-induced  sedation.Dosage  and  method  of  administration.  Note:  The  patient  should  be  on  a  cardiac  monitor  in  case  of  bradyarrhythmia.PhysostigmineAdult  dose.  Give  0.5–1  mg  IV  slowly  (diluted  in  10  mL  of  D5W  or  normal  saline)  over  2–5  minutes,  carefully  observing  for  improvement  or  side  effects  (especially  bradycardia  or  heart  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - accessmedicine.mhmedical.com/content.aspx?aid=1179993051
ER  -