Side effects and toxic reactions of chiral drugs: a clinical perspective.

A survey of 1850 drugs regularly prescribed reveal that 1045 are chiral. 517 of the 1045 chiral drugs are derived from natural sources or are modifications of naturally occurring compounds. Due to the stereospecificity of biological synthesis 509 (99%) of these naturally occurring drugs are obtained in a stereochemically pure form which is the biological active isomer. By contrast, 467 (88%) of the 528 drugs with a chiral center produced by chemical synthesis are used as racemates since chemical synthesis usually leads to racemie compounds unless stereospecific synthesis is employed, and only 61 are stereochemically pure drugs (Ariens 1990, Kleeman und Engel 1982, Bailey 1986). Chemically, and to an even greater extent biologically, a racemie drug is not a single compound, but a 50:50 mixture of 2 stereoisomers. In view of the widespread therapeutic use of racemic drugs and the pronounced differences that can exist both in the activity and the disposition of the enantiomers contained in racemates, interest in the stereochemical aspects of action, disposition, side effects and toxicity of racemic drugs and the implications for drug use has grown in recent years. No generalizations can be made concerning whether and to what extent the activity, in either qualitative or quantitative terms, differs between stereoisomers. It is not unusual for the stereoisomer of a drug to have a high degree of stereoselectivity for one action, but no stereoselectivity for another action. The more active enantiomer is designated as eutomer, whereas the enantiomer with the lesser pharmacological activity is the distomer (Lehmann et al. 1976). The situation that both enantiomers have the same therapeutic potency, side effects and toxicity is rather seldomly encountered.