The dose of a drug required to produce a specific response in an individual is the individual effective dose. Genetic polymorphisms are responsible for three major types of inter-individual variations that can influence pharmacotherapy.4,5 Genomic controls are responsible for individual differences in Phase I (i.e., oxidation and reduction) and Phase II (i.e., conjugation) reactions responsible for drug metabolism or biotransformation (i.e., pharmacokinetic variations).
Genomic controls are also responsible for altered drug receptors or altered signaling pathways once a drug-receptor complex is formed (i.e., pharmacodynamic effects). As well, genomic controls are responsible for idiosyncratic drug effects. These are unusual, unpredictable reactions observed in a small number of individuals resulting from an interaction between a drug and some unique aspect of an individual’s physiologic/biochemical makeup.
When a drug’s usual effect is produced at an unexpectedly high dose, the individual is said to be hyporeactive; when the usual effect of a drug is produced at an unexpectedly low dose, the person is said to be hyperreactive. An individual who experiences decreased response to a drug as a result of prior exposure is said to have developed tolerance. Tolerance that develops rapidly, following the administration of only a few doses of a drug, is defined as tachyphylaxis.