4. Pharmacology

Question 1

Chirality

Answer 1

Right and left hands are mirror images of each
other but cannot be superimposed when the palms are facing in the same direction

These enantiomers have the capacity to rotate polarized light
and so are also known as optical isomers.

Drugs such as bupivacaine and prilocaine are racemic mixtures. The more favourable
safety profile of single enantiomer preparations has given chirality more immediate
anaesthetic relevance.

Chiral drugs that are found in nature are usually single enantiomers because they
are synthesized enzymatically in reactions that are stereospecific. Such drugs
include adrenaline (epinephrine), atropine, cocaine, ephedrine, hyoscine, morphine
and noradrenaline (norepinephrine). All are levorotatory and still have the
designation (l).

Question 2

Drugs with chirality

Answer 2

Bupivacaine:
the S (−) enantiomer has less affinity for,
and dissociates quicker from, myocardial sodium channels.
The risk of cardiovascular and CNS toxicity is reduced.
The S (−) enantiomer also exerts some vasoconstrictor activity.

2. Ropivacaine: this is the pure S (−) enantiomer of propivacaine. It also has a safer
   cardiovascular profile in overdose
3. Lidocaine: this is achiral.
4. Ketamine: the S (+) enantiomer has a greater affinity for its main binding site
   (the NMDA receptor) and is up to four times as potent as the R (−) form.
   Its administration is also associated with fewer emergence and psychotomimetic
   phenomena.