Am.  Jour.'Pharm.  \ 
March,  1908.  J 
Therapeutic  Virtues  of  Digitalis. 
109 
searches  bearing  on  this  point  is  that  of  Fraenkel  (Archiv.fur  Exper. 
Path,  und  Pharm.,  Vol.  li,  p.  84).  This  observer  found  that  after  the 
administration  of  minimum  lethal  doses  of  digitoxin  no  slowing  of  the 
pulse  occurred  for  from  twelve  to  twenty- four  hours,  but  when  the 
effect  of  the  drug  began,  it  passed  through  the  therapeutic  stage  into 
poisoning  and  even  death.  He  found  that  it  was  well-nigh  impossible 
to  produce  from  a  single  dose  of  digitoxin  any  therapeutic  slowing  of 
the  pulse  which  was  not  followed  later  by  toxic  manifestations; 
in  other  words,  the  border-line  between  the  therapeutic  dose  and  the 
poisonous  dose  was  so  extremely  narrow  that  no  one  could  walk 
therein.  By  the  administration,  however,  of  comparatively  small 
doses  for  several  days,  he  could  produce  easily  a  marked  slowing  ol 
the  pulse.  But  here  again  the  peculiar  persistency  and  tendency  to 
show  a  cumulative  effect  of  digitoxin  above  the  other  principles 
became  manifest.  For  instance,  whereas,  he  could  continue  adminis- 
tering one-half  of  the  lethal  dose  of  digitalin  daily  for  many  weeks 
without  toxic  symptoms,  one-third  of  the  fatal  dose  of  digitoxin 
repeated  daily  for  three  days  caused  violent  poisoning. 
Again,  as  before,  these  results  have  been  confirmed  by  clinical 
experience.  Hatcher  (Jour.  Amer.  Med.  Assoc.,  Vol.  xlvii,  p.  2059) 
says,  in  speaking  of  digitoxin:  "Among  these  disadvantages  are : 
its  insolubility  in  water  and  consequent  irritant  action,  slowness  to 
act,  and  tendency  to  cumulative  effect  ;  its  proneness  to  decomposi- 
tion, whereby  toxiresin  is  formed ;  the  narrow  margin  between  the 
effective  dose  and  that  which  causes  cumulative  effects  on  con- 
tinued use  ;  and  its  marked  vaso-constrictor  effects,  which  may  or 
may  not  be  objectionable,  dependent  on  the  case  in  hand.  .  .  . 
This  insolubility  also  seems  to  be  responsible  for  the  delay  of  forty- 
eight  hours  or  more  in  inducing  the  cardiac  effects." 
For  the  above  reasons  it  would  seem  extremely  doubtful  that 
digitoxin  represents  digitalis  either  quantitatively  or  qualitatively  ; 
for  while  in  a  general  way  the  effects  of  digitoxin  upon  the  circula- 
tion are  similar  to  those  of  digitalis,  there  are  certain  differences 
which  may  seem  slight,  but  yet  which  are  of  great  practical  impor- 
tance. Kakowski  (Archiv.  Inter nat.  die  Pharmac.  und  die  Therapy 
in  a  series  of  studies  upon  the  isolated  heart  of  both  the  frog  and 
the  mammal,  reached  the  conclusion  that  none  of  the  principles  thus 
far  found  in  digitalis  had  the  same  effect  upon  the  heart  muscle  as 
did  the  tincture  or  infusion  of  digitalis.  The  principles  he  studied 
included  digitoxin,  digitalein  and  digitalinum. 
