Chemical idiosyncrasy refers to a genetically determined abnormal reactivity to a chemical. The response observed is usually qualitatively similar to that observed in all individuals but may take the form of extreme sensitivity to low doses or extreme insensitivity to high doses of the chemical.
A classic example of an idiosyncratic reaction is provided by patients who exhibit prolonged muscular relaxation and apnea (inability to breathe) lasting several hours after a standard dose of succinylcholine.
Succinylcholineusually produces skeletal muscle relaxation of only short duration because of its very rapid metabolic degradation by an enzyme that is present normally in the bloodstream called plasma butyrylcholinesterase (also referred to as pseudocholinesterase). Patients exhibiting this idiosyncratic reaction have a genetic polymorphism in the gene for the enzyme butyrylcholinesterase, which results in a protein that is less active in breaking down succinylcholine. Family pedigree and molecular genetic analyses have demonstrated that the presence of low plasma butyrylcholinesterase activity is due to the presence of one or more single-nucleotide polymorphisms (SNPs) in this gene.
It is now recognized that many of the so-called idiosyncratic adverse drug reactions and many drug–drug interactions are due to specific genetic polymorphisms in drug-metabolizing enzymes, transporters, or receptors.