Isomerism and anaesthetic drugs.
Isomers are two or more different substances with the same molecular formula (i.e., the same number of different types of atoms). There are two main types of isomerism: 1) structural isomerism, and 2) steroisomerism. Structural isomers (e.g., enflurane and isoflurane) have different molecular structures, and usually behave like different drugs. Occasionally, structural isomers are interconvertible (i.e., they are tautomers or dynamic isomers); this occurs with the barbiturates and midazolam. Steroisomers have identical structures, but a different configuration or spatial arrangement. Stereiosomerism in drugs is often due to chirality or "handedness"; i.e., the presence of right-handed (R)- and left-handed (S)- forms of drugs which are nonsuperimposable mirror images ("enantiomers"). Approximately 60% of anaesthetic agents are chiral drugs; some of these are administered as single enantiomers. However, many synthetic chiral drugs are equal mixtures of (R)- and (S)-isomers, and there are often important differences in their activity and pharmacokinetics. Halothane, enflurane, and isoflurane are chiral drugs with different anaesthetic potencies. Similar differences occur with intravenous anaesthetics; thus, (S) (+)-ketamine causes fewer psychotic emergence reactions, less agitated behaviour, and better intraoperative amnesia and analgesia than its enantiomer. Some local anaesthetics are administered as chiral mixtures; the (S)-isomers have a longer action because of enhanced vasoconstriction. (S)-prilocaine is more slowly metabolized than its enantiomer, while (S)-bupivacaine may produce less cardiotoxicity than (R)-bupivacaine. These differences suggest that some anaesthetic drugs (particularly ketamine and chiral local anaesthetics) should be administered as single enantiomers. In recent years, their synthesis has been greatly simplified, and almost all new drugs may soon be introduced in this form.(ABSTRACT TRUNCATED AT 250 WORDS)
Calvey
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University Department of Anaesthesia, University of Liverpool, Royal Liverpool Hospital, UK.
D000759:Adjuvants, Anesthesia / Q000737:chemistry; D000777:Anesthetics / Q000737:chemistry* / Q000493:pharmacokinetics; D000778:Anesthetics, Dissociative / Q000737:chemistry / Q000493:pharmacokinetics; D018685:Anesthetics, Inhalation / Q000737:chemistry / Q000493:pharmacokinetics; D018686:Anesthetics, Intravenous / Q000737:chemistry / Q000493:pharmacokinetics; D000779:Anesthetics, Local / Q000737:chemistry / Q000493:pharmacokinetics; D001463:Barbiturates / Q000737:chemistry; D002045:Bupivacaine / Q000737:chemistry / Q000493:pharmacokinetics; D004737:Enflurane / Q000737:chemistry / Q000493:pharmacokinetics; D006221:Halothane / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007530:Isoflurane / Q000737:chemistry / Q000493:pharmacokinetics; D007536:Isomerism; D007649:Ketamine / Q000737:chemistry / Q000493:pharmacokinetics; D008874:Midazolam / Q000737:chemistry; D011318:Prilocaine / Q000737:chemistry / Q000493:pharmacokinetics; D013237:Stereoisomerism
D000759:Adjuvants, Anesthesia; D000777:Anesthetics; D000778:Anesthetics, Dissociative; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D001463:Barbiturates; D011318:Prilocaine; D007649:Ketamine; D004737:Enflurane; D007530:Isoflurane; D008874:Midazolam; D006221:Halothane; D002045:Bupivacaine