460  Cardiac  Stimulants  and  Depressants.  { 
Am.  Jour.  Pharm. 
October,  1910. 
stimulation,  show  a  very  sharp  line  between  their  therapeutic  and 
toxic  doses.  A  dose  slightly  less  than  that  which  is  required  to 
cause  death  causes  only  slight  toxic  phenomena.  With  the  drugs 
of  this  class,  on  the  contrary,  the  toxic  symptoms  are  manifested 
even  under  the  influence  of  comparatively  small  doses  and  these 
increase  gradually  until  death  is  reached.  For  this  reason,  the 
dosage  of  these  drugs  is  not  as  sharply  defined  as  that  of  the  drugs 
previously  considered,  and  it  is  necessary,  in  making  a  standard  for 
these  drugs,  to  arbitrarily  fix  a  period  of  time  within  which  the 
animal  must  die,  if  the  drug  is  to  be  considered  up  to  standard. 
This  period  has  been  fixed  as  three  hours,  as  we  have  found  that 
ordinarily  a  dose  which  will  eventually  prove  fatal  will  do  so  within 
this  time. 
The  heart  depressants  differ  from  the  drugs  of  the  digitalis 
series  in  another  respect,  each  of  them  producing  evident  effects 
when  given  in  sublethal  doses.  Aconite  causes  in  many  cases 
nausea,  which  is  shown  in  the  guinea  pig  by  violent  retching.  As 
far  as  our  observations  are  concerned,  this  animal  never  vomits. 
The  irritant  effect  is  also  shown  by  the  tendency  of  this  drug  to 
cause  diarrhoea. 
Gelsemium  is  likely  to  cause  convulsions  and  these  are  frequently 
followed  by  paralysis,  even  in  cases  in  which  the  animal  eventually 
recovers.  The  guinea  pig  poisoned  with  gelsemium  lies  on  the 
side,  moving  the  legs  feebly  from  time  to  time  and  breathing 
irregularly,  and  frequently  only  at  long  intervals.  This  paralysis 
may  not  come  on  until  an  hour  or  so  after  the  administration  of 
the  drug,  and  in  this  case,  recovery  is  likely  to  take  place.  If 
the  paralysis  occurs  within  twenty  minutes  of  the  time  the  drug  is 
administered,  the  dose  will  generally  prove  fatal. 
Veratrum  stands  between  aconite  and  gelsemium  in  regard  to 
these  phenomena,  causing  convulsions  less  frequently  than  the  latter, 
but  being  very  likely  to  cause  paralysis.  Retching  and  diarrhoea, 
although  not  so  common  as  with  aconite,  are  frequently  seen.  It 
might  be  mentioned  in  this  connection  that,  of  the  drugs  spoken  of 
in  the  previous  article,  apocynum  frequently  causes  paralysis,  even 
in  animals  which  eventually  recover,  and  squill  and  convallaria  often 
cause  convulsions.  Digitalis  is  much  freer  from  these  sublethal 
toxic  phenomena. 
The  drugs  which  have  been  mentioned  as  causing  death  by 
failure  of  the  respiration  can  all  be  standardized  by  chemical  means, 
