Classify and describe the mechanisms of drug interactions with examples.
Candidates with a well organised answer scored highly. A list of drug interactions was not sufficient to pass, as the question asked to 'describe' the mechanism of drug interactions. Some candidates described the interaction but did not give examples. Common mistakes included using incorrect examples for a particular mechanism and describing the mechanism of action of drugs instead of drug interactions
Tghis question is identical to Question 9 from the second paper of 2015, except that time the examiners actually gave a relatively detailed comment on what was expected. In summary, the answer should probably be separated into some combination of pharmacokinetic and pharmacodynamic drug-drug effects. A sensible-sounding classification system and some examples are listed here.
Mechanism | Examples |
Absorption interactions | |
Formation of insoluble complexes |
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Inhibition of active transporters |
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Inhibition of efflux transporters |
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Distribution interactions | |
Competition for transport protein binding sites |
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Metabolic interactions | |
Competition for the same CYP450 enzymes |
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Inhibition or induction of metabolic enzymes |
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Interactions influencing elimination | |
Competition for active transport |
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Interference with solubility |
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Mechanism | Examples |
Homodynamic: Binding to the same receptor site |
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Allosteric modulation: binding to the same receptor, but at different sites |
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Heterodynamic: Binding to different receptors, but affecting the same second messenger system |
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Second messenger effects: Binding to different receptor/messenger systems, but having effect on the same physiological process |
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Additive or opposing physiological effects: different receptor systems and physiological mechanisms, all acting on the same clinical effect |
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Interference with the control mechanism of a physiological process which is the target of another drug |
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Abdel-Magid, Ahmed F. "Allosteric Modulators: An Emerging Concept in Drug Discovery." (2015). ACS Med. Chem. Lett., 2015, 6 (2), pp 104–107
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Huang, Shiew-Mei. "Drug-drug interactions." Applications of Pharmacokinetic Principles in Drug Development. Springer, Boston, MA, 2004. 307-331.
Snyder, Ben D., Thomas M. Polasek, and Matthew P. Doogue. "Drug interactions: principles and practice." Australian prescriber 35.3 (2012): 85-8.
Perucca, E., et al. "Interaction between phenytoin and valproic acid: plasma protein binding and metabolic effects." Clinical Pharmacology & Therapeutics 28.6 (1980): 779-789.