The relationship between chronic disease and drugs/toxins—how important is negative disease-drug synergy?

The interaction of diseases with drugs and toxins may result in significantly worse outcomes in a forensic context when i) chronic diseases cause toxicity by increasing drug levels due to reduced renal clearance or slowed hepatic breakdown, and ii) drugs exacerbate underlying lethal mechanisms. In other words, ‘negative disease-drug synergy’ may result in increased drug toxicity and/or greater organ dysfunction despite the use of standard dosages. This is yet another confounding factor to be considered in the interpretation of postmortem toxicological results, as underlying illness and disease states may significantly alter drug availability and physiological responses.