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11 Computational Toxicology in Drug Discovery: Opportunities and Limitations
3. Molecular mechanisms causing the opposite biological effects. For example, an
alpha adrenergic agonist increases the blood pressure, and angiotensin converting enzyme inhibitor reduces the blood pressure.
Additive pharmacodynamic effects are determined by:
1. Identical biological effects, if these compounds provide the same biological
effect. For example, the blood pressure reduction or increase of QT interval.
2. Mechanisms of action providing the common biological effect, if these compounds have different molecular mechanisms of action, causing the common
biological effect. For example, a diuretic and angiotensin-converting enzyme
inhibitors decrease the blood pressure, and inhibitors of carbamoyl phosphate
synthetase and acyl-CoA dehydrogenase induce hyperammonemia.
The algorithms for the analysis of pairwise drug-drug interactions are also useful
for the analysis of interactions between several substances. The example of evaluFig. 11.3  Overall flowchart to identify pharmacodynamic drug interactions