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last week aya presented the case of a young woman who took an unspecified amount of paracetamol & aspirin tablets
she phoned her GP fairly soon after ingesting the tablets, and come into casualty soon after
she had a history of self-harm but no previous overdoses
she is managing (?) to study & work part-time
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we discussed the critical issue of timing of the overdose
this is due to the practicalities of using the paracetamol OD nomogram - see below: this can be found in the beginning of the BNF
we said:
- the graph does not start until 4 hours has been reached
- levels can be expressed in 2 different units, either mg/L or mmol/L, clearly it is crucial to know which is used in your lab
- the high risk line includes people who have had their liver enzymes induced or who are malnourished
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we had a short discussion about the nature of drug metabolism
in essence metabolism makes compounds more water-soluble, and hence more likely to be excreted via the kidneys
the enzymes involves are part of the cytochrome p450 system
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we also talked about how not very nice it is to die from paracetamol poisoning
the key measurements on day 2 are prothrombin time (or INR), pH, lactate & creatinine (NB not AST, ALT etc)
any deterioration necessitates a call to your local liver centre
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we touched on the mechanism of the toxicity
paracetamol is normally metabolised by adding a polar group, mostly sulphate or glucuronide
it can also be metabolised to NABQI (N-acetyl-benzoquinoneimine) [normally 10%]
this is a dangerous chemical as it reacts with DNA & cell proteins [it is a strong oxidiser]
NABQI is normally mopped up by glutathione [an anti-oxidant]
when glutathione stores are deplete, cell damage will occur
therefore the antidote is to give glutathione
glutathione is made from 3 amino acids, 2 of which are plentiful in cells
the third, cysteine, is the rate-limiting species, and this is the treatment: N-acetyl-cysteine or NAC [the N-acetyl- bit helps absorption]
the other antidote is (oral) methionine which is more proximal in the synthetic pathway
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this whole anti-oxidant pathway is worth being aware of
a lot of current research in a wide variety of conditions, from IHD to autism, involves these pathways
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we mentioned the need to give NAC IV at 3 different infusion rates
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other issues we covered:
- aspirin OD, clinical & metabolic features, and treatment (alkanise urine ± dialysis)
- high risk features for recurrent suicide attempts
- social isolation & the buffering effect of friends
Salaam
sabih
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