a 20-year-old woman with a mixed overdose

apologies for the hiatus
_ _ _

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
_ _ _

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

_ _ _

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

_ _ _

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

_ _ _

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

_ _ _

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

_ _ _

we mentioned the need to give NAC IV at 3 different infusion rates

_ _ _

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