Pharmacology for Anaesthesia and Intensive Care

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Isomerism

Isomerism is the phenomenon by which molecules with the same atomic formulae

have different structural arrangements – the component atoms of the molecule are

the same, but they are arranged in a different configuration. There are two broad

classes of isomerism:


Structural isomerism


Stereoisomerism

Structural isomerism

Molecules that are structural isomers have identical chemical formulae, but the order

of atomic bonds differs. Depending on the degree of structural similarity between the

isomers, comparative pharmacological effects may range from identical to markedly

different. Isoflurane and enflurane are both volatile anaesthetic agents; prednisolone

and aldosterone have significantly different activities, with the former having gluco-

corticoid and mineralocorticoid actions but the latter being predominantly a min-

eralocorticoid. Isoprenaline and methoxamine have different cardiovascular effects,

with methoxamine acting predominantly viaα-adrenoceptors and isoprenaline act-

ing viaβ-adrenoceptors. Dihydrocodeine and dobutamine are structural isomers

with very different pharmacological effects; it is little more than coincidence that

their chemical formulae are identical (Figure5.1).

Tautomerism

Tautomerism refers to the dynamic interchange between two forms of a molecular

structure, often precipitated by a change in the physical environment. For example,

midazolam, which is ionized in solution at pH 4, changes structure by forming a

seven-membered unionized ring at physiological pH 7.4, rendering it lipid-soluble,

which favours passage through the blood–brain barrier and increases speed of access

to its active sites in the central nervous system (see Figure17.1). Another com-

mon form of isomerism is the keto-enol transformation seen in both morphine and

thiopental.

Stereoisomerism

Stereoisomers have both the same chemical constituents and bond structure as

each other but a different three-dimensional configuration. There are two forms of

stereoisomerism: