382  Digitoxin,  Principle  of  Digitalis.  {AmAiS.Srm" 
of  the  leaf  is  wholly  destitute  of  the  representative  principle 
of  the  leaf,  and  consequently  of  medicinal  worth ;  yet  there 
are  physicians  who  use  the  infusion  of  the  leaf  to  the  exclu- 
sion of  its  other  preparations.  Against  this  fact  it  is  contended 
[Pharmaceutische  Rundschau,  1898,  603,  vide  Am.  Jour.  Pharm., 
1899,  145)  that,  while  "pure  digitoxin  is  insoluble  in  water,  yet  from 
the  infusion  of  digitalis  considerable  quantities  are  obtainable,"  and 
in  explanation  of  this  seeming  paradox  it  is  claimed  that  the  other 
glucosides  of  the  leaf  form  digitoxin  on  its  digestion  with  water.  But 
how  this  makes  water-insoluble  digitoxin  soluble  in  water  is  not 
explained.  The  infusion  made  by  cold  water  maceration  (which  can 
contain  no  digitoxin)  is  better  clinically,  in  the  writer's  experience, 
than  the  hot  water  product  (A.  J.  P.,  1892,  361). 
Now,  without  denying  that  digitoxin  may  be  the  most  distinctive 
chemical  substance  in  digitalis  leaf,  it  is  very  clear,  from  the  recently 
reported  experiments  of  Dr.  Karl  Hofmann  {Wiener  klinische 
Wochenschrift,  1896,  No.  42,  939,  vide  The  American  Journal  of  the 
Medical  Sciences,  1897,  107),  and  the  pharmacological  results  pre- 
viously given  by  the  writer  in  this  journal,  that  the  entire  thera- 
peutic activity  of  the  leaf  cannot  be  due  to  digitoxin. 
Dr.  Hofmann  reports  results  had  with  the  use  of  digitoxin  in 
fifty-nine  cases — three  instances  by  the  mouth,  thirty-seven  by  sub- 
cutaneous injection  and  nineteen  by  enemata.  He  confirms  pre- 
vious investigators  in  referring  to  its  insolubility  in  water  and  the 
vigorous  local  irritation  caused  by  its  use.  The  injections  are  fol- 
lowed by  local  burning  pain,  lasting  from  one-half  to  three  or 
four  hours,  and  redness  for  two  or  three  days,  which  is  sensitive 
to  pressure.  Inappetite,  nausea,  vomiting  and  pain  in  the  epigas- 
trium occurred  in  one-fourth  the  cases,  whether  subcutaneous  in- 
jections or  enemata  were  administered.  The  most  remarkable 
fact,  however,  was  the  length  of  time  reported  as  having  elapsed 
before  physiological  effect  was  manifested.  After  the  first  dose, 
six  hours  were  required  to  increase  pulse-force  and  lessen  dyspnoea, 
while  twelve  hours  were  required  to  produce  diuresis.  With 
enemata  these  changes  required  twenty-four  to  thirty-six  hours. 
From  a  therapeutic  point  of  view,  it  is  clearly  impossible  to 
believe  that  a  drug  or  preparation  that  yields  physiological 
effects  in  about  thirty  to  sixty  minutes  has  for  its  most  important 
constituent  a  proximate  principle,  whose  physiological  effects  are 
not  manifested  in  from  six  to  thirty-six  hours. 
