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1 SBA on isomerism
Viva
8 viva questions
- Core
Is R the same as dextrorotatory?
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No — there is no link between the two. R/S is a calculated, structural label, assigned from CIP priority rules applied to the chiral centre’s substituents. Dextrorotatory (+) is a measured, empirical property, observed with a polarimeter. An S-configured molecule can rotate light either clockwise or anticlockwise — you cannot predict one from the other without measuring or calculating it directly. This exact conflation is the single most consistently penalised error in this topic.
- Core
Why is levobupivacaine called “levo-” if that isn’t a description of its R/S configuration?
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Because “levo-” names its levorotatory optical activity — measured rotation — not its R/S configuration. It happens to also be the S-enantiomer of bupivacaine, but the name is a naming convention, not a stereochemical shortcut. The same trap runs the other way with dexmedetomidine, which is the S-enantiomer of medetomidine despite the “dex-” prefix ordinarily evoking dextrorotatory activity.
- Core
Etomidate is marketed as a single isomer. Why does that matter clinically?
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Etomidate’s anaesthetic effect resides predominantly in the R(+) isomer, roughly five times as potent as S(−). Marketing the active isomer alone avoids diluting every dose with an isomer contributing little useful effect. That stereoselectivity is itself part of the evidence that GABAA receptors are etomidate’s site of action.
- Applied
Atracurium has four chiral centres. Why isn’t there sixteen stereoisomers in the vial?
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Four chiral centres give a theoretical maximum of 24 = 16 stereoisomers, but atracurium is an internally symmetric molecule, so several of those theoretical configurations duplicate one another — only 10 distinct structures actually exist. Those 10 separate further into three geometric groups by ring configuration: roughly 50-55% cis-cis, 35-38% cis-trans and 6-7% trans-trans.
- Applied
Cisatracurium doesn’t cause histamine release the way atracurium does. What does that tell you?
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That the histamine-releasing property is itself stereospecific — a property of specific isomers within the atracurium mixture, not of the drug class as a whole. Cisatracurium, the isolated 1R-cis–1′R-cis isomer, is about four to five times as potent as atracurium and does not cause clinically significant histamine release at clinical doses.
- Applied
Is the S-enantiomer of a local anaesthetic always the safer choice?
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Cardiotoxically, generally yes within the bupivacaine family — the R-enantiomer is more cardiotoxic than S. But it is not a free upgrade on every axis: the S-enantiomers of mepivacaine and bupivacaine are also metabolised more slowly by the liver than their R counterparts, meaning somewhat greater systemic accumulation on a prolonged infusion. A wider safety margin, not an unconditional one.
- Applied
Name a drug where the two enantiomers do genuinely different jobs, not just different amounts of the same job.
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Methadone — L-methadone is an opioid μ-receptor agonist, D-methadone a potent NMDA-receptor antagonist, acting at entirely different targets. Or dobutamine — the (−) enantiomer is an α1-agonist, the (+) enantiomer a competitive α1-antagonist at the very same receptor, with the drug’s net effect reflecting the balance struck between them. Sotalol is a related but distinct pattern: both enantiomers share class III activity, but only the levorotatory isomer adds β-blockade, and the dextrorotatory isomer alone carries its own mortality signal after myocardial infarction.
- Core
Is a racemic drug automatically half as potent as the pure active isomer?
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Not necessarily. The other enantiomer is not always simply inert — it can be independently toxic, act at a completely different target, or contribute a genuinely complementary effect (as in methadone, dobutamine and sotalol). Purifying to a single isomer removes whatever the other enantiomer was contributing, for better or worse — it changes the drug’s overall profile rather than just concentrating it.