The Pharmaceutical Journal Vol 264 No 7096 p726
May 13, 2000 Letters

Paracetamol

No surprises

From Mr R. J. Schmidt, MRPharmS

SIR,-The report linking frequent use of paracetamol with increased asthma incidence and severity (PJ, March 25, p459) provides no surprises. As usual I heard the story first in the national news and, even before reading the more detailed story in the PJ, immediately linked the observed clinical outcome to glutathione depletion as a possible cause. Having had occasion to prepare review articles on oxidative stress and redox homeostasis in lung toxicology¹ and in paracetamol poisoning,² the link was easily made.
Paracetamol probably represents the largest and most common self-inflicted insult we make to our glutathione status. It is reasonable to suppose that in any given population there will exist at one end of a continuum individuals who are well able to tolerate the insult, others who come very close to tipping over the edge, and others still who do tip over the edge. For those who do tip over the edge the outcome will then depend upon the tissue so affected because different tissues will also have different capacities to maintain gluthathione status and hence redox homeostasis. On this basis, it is entirely predictable that paracetamol use should lead to an increase in the incidence and severity of any disease with an oxidative stress-related aetiology. Asthma is just one such disease. We should also be looking at the effects of para-cetamol use on the incidence of cardiovascular disease, neurodegenerative disease, cancer, and indeed all chronic inflammatory disorders whose incidence increases in old age.
Perhaps the time has come to revisit the possibility of using formulations of paracetamol with N-acetylcysteine, an agent that leads to repletion of glutathione, in those at risk?

Richard J. Schmidt
Barnoldswick, Lancashire

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