A commentary on pharmacogenomics ; What can it do ?

T he Clreat Paracelsus (Philipus Aureolus Theophrastus Bonihastus von Hohenheini-Paracelsus, 1493-1541) is remembered by toxicologists for his famous quote: "All substances are poisons; there is none which is not a poison. Tlie right dose differtntiates a poison from a remedy-"' Intieed, tiic l)iisic principle from the quotation still applies today. The right dose of morphine that will produce a hlood level of approximately 0.07 mji,/L to 0.083 mg/L is essential for the relief of pain. An overdose that results in a markedly increased blood level (0.2 mg/L to 2.3 nig/L) can cause death line to central nervous system depression.In general, the same applies to all chemical substances. As an im|)ortimt exception to Paracelsus" statement, however, there are instances in vvliich a tlrug should be avoided completely. An example is found in the administration of succinylcholine as a skeletal muscle relaxant in surgeiy patients. Most patients can convert succinylcholine into inert metabolites through an enzyme called [iseudochohncsterase because most patients possess tu'o alleles for die common gene that can produce active enzyme. A certain small percentage of patients, however, carries the genes that are aberrant or silent and, thus, either produce protein (enzyme) that is defective in its fimction or cannot produce the protein that is ciipahle of inactivating administered succinylcholine at all. Thus, these patients expire or suffer severe sequelae from ailministnition ofthe drug.'