Am.  Jour.  Pharm. 
June,  1917. 
Current  Literature. 
289 
ment  also  seems  to  hold  true  for  man.  The  untoward  results  that 
have  been  reported  in  the  literature  from  the  use  of  novocaine  in 
operations  about  the  head  and  face  might  well  be  accounted  for  by 
the  fact  that  absorption  may  be  very  rapid,  as  for  example  in  dental 
operations  when  the  injection  is  made  in  a  region  well  supplied  with 
blood  vessels,  so  that  administration  directly  into  the  circulation  is 
not  unlikely  to  occur,  and  when  injected  in  this  way  the  toxicity  is 
greater  than  when  given  subcutaneously.  Individual  susceptibility 
is  marked  in  both  animals  and  man.  This  may  account  for  some  of 
the  fatalities  reported  in  the  literature. 
In  addition  to  idiosyncrasy,  age  seems  to  be  a  factor  in  man  in  the 
production  of  fatal  results  with  novocaine.  In  the  three  cases  re- 
ported by  Scandola,  1915,  the  ages  of  the  men  were  69,  75,  and  80 
years,  respectively.  In  cases  having  low  blood  pressure,  or  cardiac 
disease,  novocaine  should  be  used  with  caution,  inasmuch  as  in  the 
laboratory  experiments  it  has  been  shown  to  have  a  depressing  effect 
upon  the  heart  muscle  when  large  doses  are  given. 
The  administration  of  hyoscine,  previous  to  the  use  of  a  local 
anesthetic  agent,  is  sometimes  advised.  If  it  is  given  before  either 
cocaine  or  novocaine,  it  may  act  as  a  synergistic  agent  in  depressing 
the  respiration.  In  order  to  prevent  the  absorption  of  novocaine 
from  the  subcutaneous  tissues,  epinephrine  is  employed.  Epineph- 
rine is  a  relatively  unstable  agent,  especially  in  alkaline  solutions. 
It  is  not  unlikely,  therefore,  that  unless  the  epinephrine  which  is  used 
with  novocaine  is  active,  general  symptoms  may  arise  from  the  ad- 
ministration of  novocaine  as  a  local  anesthetic  agent. 
The  melting  point  of  novocaine,  as  determined  from  the  examina- 
tion of  10  samples  used  in  this  investigation,  varied  from  1530  to 
1 57°  C.  The  relative  toxicity  of  cocaine  and  novocaine,  as  shown  by 
animal  experiments,  varies ;  the  variation  being  dependent  mainly 
upon  the  animal  employed  as  test  animal.  The  relative  toxicity  of 
cocaine  and  novocaine  for  various  animals  when  given  subcutane- 
ously is  as  follows:  For  frogs  (Rana  pipiens)  the  ratio  is  1.0  to 
1.4;  mice,  5.5  to  1  ;  rats,  10  to  1 ;  guinea  pigs,  10  to  1  ;  and  rabbits, 
5.3  to  1.  When  given  intravenously  to  rabbits,  the  ratio  of  toxicity 
of  cocaine  to  novocaine  is  3.9  to  1.  When  given  intravenously  the 
rate  of  administration  is  a  factor  in  modifying  the  toxicity.  The 
subcutaneous  administration  of  large  sublethal  doses  of  novocaine  in 
the  dog  and  cat  causes  marked  general  symptoms  which  rapidly  sub- 
side. The  ratio  of  the  toxicity  of  cocaine  and  novocaine  for  mice, 
when  fed  on  cakes  containing  these  substances,  is  much  wider  than 
