^MiJShJfiS™'}      Standardization  of  Preparations.  ill 
occurring  in  the  drug.  More  recent  experience,  however,  has  shown 
that  the  active  principles  of  digitalis  act  primarily  on  the  heart  and 
blood-vessels,  and  all  other  effects  are  secondary;  but  in  many  cases 
the  secondary  action  of  the  drug  is  undesirable. 
Of  the  active  principles  of  digitalis,  digitoxin  is  by  far  the  most 
important  and  possesses  the  heart-stimulating  property  to  a  much 
greater  degree  than  any  of  the  other  principles. 
The  cardiac  action  of  digitalis  is  its  most  important  effect  and 
one  which  has  been  studied  very  widely,  particularly  on  the  heart 
of  the  frog.  The  action  of  digitalis  on  the  frog's  heart  is  very 
characteristic.  After  administration  it  can  be  observed  that  the 
rhythm  of  the  heart  is  slowed  and  that  on  contraction  it  occupies 
a  smaller  volume  and  does  not  dilate  as  fully  as  under  normal  con- 
ditions. The  ventricle  is  observed  to  be  whiter  during  contraction, 
and  on  dilation  does  not  become  so  red.  A  tracing  forms  a  plateau 
when  the  heart  is  in  systole. 
A  frog  killed  by  digitalis  dies  with  its  heart  in  systole.  This 
happens  very  rarely,  if  at  all,  with  the  mammalian  heart,  and  was 
thought  for  a  long  time  to  be  a  distinguishing  feature  between  the 
action  of  digitalis  on  cold-blooded  and  warm-blooded  animals. 
However,  recent  research  shows  that  the  changes  which  take  place 
in  a  frog's  heart  under  digitalis  are  very  closely  related  to  those 
taking  place  in  the  mammalian  heart.  We  can  divide  the  action  of 
digitalis  on  the  mammalian  heart  into  three  stages :  First,  the  thera- 
peutic stage,  in  which  the  rhythm  of  the  heart  is  slowed  and 
there  is  an  increased  and  prolonged  systole.  The  ventricles  more 
nearly  empty  themselves  of  blood,  and  by  their  prolonged  con- 
traction maintain  a  higher  blood-pressure  in  the  vessels  than  nor- 
mally. In  the  second  stage,  the  rhythm  of  the  heart  and  pulse  is 
very  slow  and  becomes  irregular.  During  diastole  the  ventricles 
dilate  more  fully,  while  the  systole  is  not  so  regular  and  many  times 
weaker,  so  that  more  blood  remains  in  the  heart  than  before  the 
drug  was  administered.  This  serves  to  distinguish  the  first  and 
second  stages;  namely,  in  the  first  stage  more  blood  is  pumped  out 
or  expelled  by  the  ventricle  than  normal ;  in  the  second  stage,  less 
blood  is  thrown  out  than  normal. 
The  important  clinical  observation  which  distinguishes  the  one 
stage  from  the  other  is  the  irregularity  of  the  pulse.  When  this 
occurs,  the  action  of  the  drug  is  reaching  the  second  stage  and 
should  be  immediately  withdrawn. 
