370 
Standardisation  of  Drugs. 
j  Am.  Jour.  Pharni. 
1     August,  1910. 
toxic  doses  are  given  intravenously.  If  this  is  done,  the  animal 
goes  through  all  the  stages;  but  even  in  this  case,  several  hours 
are  required  until  death  occurs,  no  matter  how  much  of  the  drug 
is  given." 
1  he  latter  part  of  this  statement  does  not  apply  to  the  cat,  nor 
does  it  apply  to  strophanthin  so  far  as  I  am  aware,  nevertheless, 
it  is  true  that  moderate  1  doses  of  digitalis  act  much  more  slowly 
on  the  cat's  heart  than  crystalline  ouabain  does,  hence  the  interval 
that  occurs  between  the  injection  of  the  minimal  fatal  dose  and  the 
death  of  the  animal  is  longer  with  digitalis  than  it  is  with  ouabain, 
and  a  greater  excess  of  the  digitalis  will  be  injected  during  that 
interval.  If  approximately  fifty  per  cent,  of  the  fatal  dose  of 
digitalis  is  injected  into  the  vein  and  twenty  minutes  are  allowed 
to  elapse  and  the  injection  is  then  continued  using  one  part  of 
crystalline  ouabain  in  one  hundred  thousand  parts  of  physiological 
salt  solution,  the  end  reaction  is  almost  as  sharp  as  with  ouabain 
alone,  the  interval  appearing  to  suffice  for  the  digitalis  to  exert 
almost  its  full  action  on  the  heart. 
The  extraordinary  uniformity 2  of  the  action  obtainable  with 
ouabain  and  other  digitalis  bodies  on  the  cat's  heart  calls  for  some 
comment.  We  have  been  inclined  to  think  that  this  might  be  ex- 
plained by  the  absence  of  racial  peculiarities,  due  to  the  nocturnal 
habits  of  the  cat  whereby  cross  breeding  is  almost  universal.  We 
are  endeavoring  to  explain  this  uniformity,  and  while  we  believe 
there  is  a  deeper  significance  than  the  one  just  suggested,  we  are 
not  prepared  to  go  deeply  into  a  discussion  of  this  phase  of  the 
question  at  present. 
The  fact  that  crystalline  ouabain  is  capable  of  replacing  amor- 
phous strophanthin,  as  well  as  the  digitalis  bodies  found  in  the  leaf, 
1  Massive  doses  of  digitalis  may  cause  death  in  6o  seconds,  or  about 
half  the  time  required  by  the  largest  doses  of  crystalline  ouabain.  We  believe 
that  this  extraordinary  rapidity  of  action  of  digitalis  is  attributable  largely 
to  digitalein,  which  also  acts  rapidly. 
2  Since  writing  the  preceding  statement,  which  was  based  on  a  very 
large  number  of  experiments  covering  a  period  of  several  years,  we  have 
found  a  number  of  cats  which  tolerated  doses  up  to  nearly  fifty  per  cent, 
more  than  that  stated.  We  are  unable  as  yet  to  explain  this.  As  previously 
stated,  the  only  ones  which  succumb  to  doses  below  the  standard  are  the 
excessively  fat.  The  later  observations  do  not  prevent  the  use  of  this 
method  of  standardization,  but  a  somewhat  larger  number  of  observations 
are  necessary  than  would  be  otherwise. 
