A5 Intoxication and overdose

Topic

Intoxication occurs when the body is exposed to an external substance—such as a medication, illicit drug, industrial toxin, or poison—in an amount that exceeds its normal elimination capacity. Following exposure, the concentration in the blood rises during absorption until it peaks, subsequently declining as the substance is metabolized and eliminated. In cases of massive overdose, however, this dynamic can shift when clearance mechanisms become saturated.

The liver serves as a primary route of elimination. At relatively low concentrations, it metabolizes many substances at a rate roughly proportional to their concentration: the higher the concentration, the faster the substance is eliminated. When a very high dose exceeds available metabolic capacity, the process may become saturated and reach a maximum rate. Beyond this point, increasing the concentration no longer accelerates elimination, which proceeds at a virtually constant pace. Consequently, the substance remains in the body for a longer period, and metabolic byproducts may accumulate.

Paracetamol illustrates this issue. Part of its metabolism generates a product toxic to liver cells, which is normally neutralized by glutathione. As long as sufficient glutathione is present, this product can be inactivated without causing significant damage. In cases of severe overdose, production of the toxic metabolite increases, potentially depleting glutathione stores. The unneutralized compound then binds to cellular proteins, causing destruction of liver tissue. Treatment involves an antidote designed to restore the protective capacity associated with glutathione; its efficacy is greatest when administered promptly after ingestion.

Toxicity and treatment options also depend on how the substance is distributed between the blood and the tissues. Some substances remain primarily within the bloodstream, while others accumulate extensively in the tissues, leaving only a small fraction circulating in the blood. This distinction determines the utility of dialysis: if a large proportion of the substance remains in the blood, extracorporeal clearance can significantly enhance its elimination. If the substance is primarily stored in the tissues, dialysis can only remove the small fraction present in the circulation, making it far less effective.

Furthermore, the relationship between concentration and toxic effect is not identical across all individuals. While a specific concentration may be associated with a certain fraction of the maximum effect, this value can vary depending on individual metabolic capacity and prior exposure. Tolerance acquired through repeated exposures may mean that a person requires higher concentrations to experience an effect equivalent to that of someone without prior exposure.

Therefore, assessing poisoning requires more than just measuring an isolated concentration. It is necessary to relate that concentration to the time elapsed since exposure, as the same level can pose different risks depending on when it is measured. In paracetamol poisoning, the Rumack-Matthew nomogram correlates blood concentration with the hours elapsed since ingestion to estimate the risk of liver damage and determine whether the antidote should be administered. References based on similar principles can be used for other types of poisoning.

Overall, the course of a poisoning incident depends on the amount absorbed, metabolic and elimination capacities, the distribution of the substance between blood and tissues, and the body's sensitivity to its effects. Metabolic saturation explains why a massive dose may take much longer than expected to clear; the depletion of protective mechanisms can turn metabolism into a source of harm; distribution determines whether procedures like dialysis can effectively remove the toxin; and the interplay between concentration and time allows for risk assessment and treatment guidance. Clinical practice integrates these factors to decide when to administer an antidote, accelerate elimination, or provide supportive care before the damage becomes irreversible.

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