This is such a common and complex occurrence and fraught with all sorts of potentialities that the possible permutations and combinations seem limitless. We need to keep it real.
Body drug-metabolism (or pharmacokinetics) can cause their inactivation or produce active metabolites, which may or may not have similar actions (pharmacodynamics) to the parent: they may even be more active than the parent drug, have a totally new action, or be toxic.
Human physiology, thankfully, is remarkably resilient: homeostatic mechanisms kick in to keep things at steady-state. Nevertheless, it behooves us to keep abreast of the common, the classic, and the critical (the three C’s) — in this field. Much medical error is from inappropriate drug use, and much inappropriate drug use relates to drug-drug interactions. [There is something to be said for de-prescribing, especially in the elderly].
As a rule of thumb: lipophilics to the liver; hydrophilics to the kidney.
Microsomal enzymes
- cytochrome P450
- flavin mono-oxygenase (FMO3)
Drug Metabolism
Phase I: Oxidation / Reduction / Hydrolysis of the xenobiotic (foreign chemical)
Phase II: Conjugation — if you can’t do any of the above, attach a moiety on to the parent molecule to make it more water soluble (after which, they can be excreted in the urine)
Phase III: energy-dependent excretion — do whatever it takes to force this intruder off your property
Note: Drug interactions from hepatic metabolism are nearly always due to interactions at Phase I enzymes rather than at Phase II — i.e. commonly due to interaction at cytochrome P450 enzymes, some of which are genetically absent!
