ACETOMINOPHEN

 

Overview:

  1. In  order  to  produce  toxicity   one   must  ingest  140mg / kg   or  7.5 gm  of  APAP.
     
  2. The  toxic metabolite, 5% ( probably N- acetyl - para - benzoquinonimine ), produced  by  P450,  is  detoxified  by conjugation  to gluthation . If  this  metabolite exceeds the amount of gluthation available, hepatic and  renal (not common) toxicity occur.
     
  3. The  nephrotoxicity (not common) can result from generation of reactive  APAP metabolite in the renal medulla.
     
  4. Drugs that induce P450 (phenytoin, barbiturates, antihistamines) increase toxicity, while cimetidine by competing with  P450, protects  from APAP toxicity.
     
  5. The  effect of  ETOH is variable . Acute  consumption  protects  from  toxicity  since  it  competes  with P450 , while  chronic  consumption  induces  P450 .

S & S:

Stage  1 :  ½ - 24 hrs anorexia n/v

Stage  2 : 24 - 48  hrs function RUQ Pain Reversible or hepatic ­ bili

Stage  3 :  72 - 96 hrs hepatic / renal  failure

Stage  4   : resolution  of  hepatic if stage 3 is necrosis 2ry to toxic hepatitis ­ LFT's

DX

  1. History
     
  2. APAP  serum  level   that  peak  after 4  hrs  s/p  ingestion. Thus, one cannot r/o APAP toxicity from one level only. Opiate  co-ingestion does not alter the peak serum level.

Therapy:

  1. 1) GI  lavage  if  ingested in  less than   1 hr
     
  2. AC: no  risk  of  binding  NAC  since  AC  binds  more  readily   to  APAP
     
  3. NAC:
     
    1. Serves  as  gluthation  substitute.
       
    2. Loading  is  140 mg / kg  followed  by  70 mg / kg   q 4  hrs  x  17  doses.
       
    3. The  NAC  is  most  effective  if  given  within   8 - 10  hrs ,  yet  can  be  effective up-to  24 hrs s/p  ingestion . Serum  level  of  APAP  must  be  plotted   on  Rumak - Matthew  nomogram  to guide  treatment. See nomogram elsewhere.
       
    4. NAC   is  given   with  OJ  since  it  has  rotten  egg  smell .  It  per  se  can  give  N/V and this  can  be  erroneously   interpreted  as  sign  of  toxicity .  N/V  can  be   treated  with   metoclopramide (Reglan )10 mg IV/IM.
       
    5. If  pts   hx   is  reliable   he / she   can  be  started  on  NAC . Later, the 4 hr level is drawn toguide further therapy. Pts are admitted to ICU.
       
  4. There is no need to admit APAP OD pt to ICU since there are no arrhythmias to anticipate.
     
  5. When considering cathartics, MgSulfate is preferred to Sorbitol since the latter can give N/V. Yet most clinicians prefer GoLytely - gives no electrolyte abnormalities and is not absorbed.

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