This chapter is directly related to Section D(ii) from the 2017 CICM Primary Syllabus, which expects the exam candidate to "classify and describe mechanisms of drug interaction". It is also vaguely related to the learning objectives of Section C which exhorts them develop "a general understanding of how drugs work, ... including ... drug interactions". In short, interactions between drugs can be classified as pharmacokinetic and pharmacodynamic. Pharmacodynamic drug-drug interactions are briefly described in another chapter. Here, the focus is on the mechanisms by which drugs interfere with each other's absorption, distribution, metabolism and elimination.
The topic of drug-drug interactions has appeared three times, in three identical questions:
All of these asked the candidates to "classify and describe the mechanisms of drug interactions with examples." The question was not specific for pharmacokinetic interactions, but these would surely form the bulk of the answer. Certainly they form the bulk of the published literature (comparatively speaking; one needs to dive deep into obscure textbooks to find good articles on pharmacodynamic drug-drug interactions). Of which, the best and most detailed article is probably the (free, PubMedable) paper by Cascorbi (2012). Unless otherwise referenced, the examples come straight from this paper.
Mechanism | Examples |
Absorption interactions | |
Formation of insoluble complexes |
|
Inhibition of active transporters |
|
Inhibition of efflux transporters |
|
Distribution interactions | |
Competition for transport protein binding sites |
|
Metabolic interactions | |
Competition for the same CYP450 enzymes |
|
Inhibition or induction of metabolic enzymes |
|
Interactions influencing elimination | |
Competition for active transport |
|
Interference with solubility |
|
Palleria, Caterina, et al. "Pharmacokinetic drug-drug interaction and their implication in clinical management." Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences 18.7 (2013): 601.
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.