It is important to see the role of metabolism in drug toxicity as one component of the bigger picture of all adverse reactions suffered by patients during drug therapy. One view of this picture is on Figure 8.1. Different authors and topics classify these effects in various ways, but a convenient way to look at things can be to resolve all drug adverse effects as either reversible (Type A) or irreversible (Type B). At this point, it is worthwhile being more precise over the terminology of drug adverse reactions. The term ‘toxicity’ is a loose one and it has been used flexibly in this topic so far. However it is useful when looking at drug metabolism-mediated effects to define toxicity more accurately for the cell in particular:
Irreversible change in structure leads to irreversible change in function.
The key here is ‘irreversible’ ; it follows that a process that is not irreversible is not actually . toxicity’ in the strict sense of the word. Reversible reactions are often either an intensification of the usual pharmacological response, or, as has been mentioned previously, an ‘off -target’ pharmacological effect. There are, of course exceptions: this strict definition of toxicity is fine for the cell, but is not so clear for the relationship between the patient, their organs, tissues and individual cells. Obviously, the effects of an anticancer alkylating agent are irreversible and toxic to a cell, but could ultimately save the life of the patient. Conversely, a heroin overdose reversibly inhibits central control of respiration and this leads to death, which is unarguably irreversible. In general though, it is probably fair to say that cumulative irreversible damage at the cellular level usually leads to patient morbidity and mortality.
