1. Isomerism and anesthesia
Dr S.Parthasarathy MD., DA., DNB. PhD., FICA., IDRA.
Diploma in software based statistics

2. What is isomerism ?
The property of isomerism occurs when two or more compounds have the same atomic formulae, but a different structural arrangement, which often results in different properties.
Basic types
Structural isomerism
Stereoisomerism

3. Structural isomerism
Structural isomers are molecules that have identical chemical formulae, but a different order of atomic bonds.
Same actions or different actions
Same actions -- anaesthetic volatile agents isoflurane and enflurane
Chemical structure
Different
but configuration same

4. Different actions- C18H23NO3 dihydrocodeine and dobutamine

5. Tautomerism
Tautomers are organic compounds that are interchangeable by a chemical reaction precipitated by a change in the physical environment..
Keto enol tautomerism of barbiturates
Midazolam and ph change

7. Stereoisomerism- chirality
Stereoisomerism describes those compounds which have the same molecular formula and chemical structure,
but a different three-dimensional configuration
Same chemical structure but different configuration
Non superimposable mirror images like left and right hand is chirality
Geometric
Optical

8. Chiral centre
One carbon or one quaternary N is satisfied with four different chemical groups

9. Many chiral molecules

11. Non superimposable mirror image chiral – hand

12. Geometric isomerism
Geometric isomerism or cis-trans isomerism describes the orientation of functional groups within the molecule.
Active groups – one side is cis
Two sides is trans

13. Example bromine is active !!

14. Atra and cis atra

15. Optical
Optical isomers are the same in every way, except being non-superimposable mirror images of each other.
They are also called optical isomers because they rotate the plane of polarised light either to the right, referred to as +, dextro, d or D isomer, or to the left, referred to as -, laevo (levo), l or L isomer. – enantiomer
Racemic mixture – 1:1 of dextro and laevo

16. D molecules

17. More recently, this classification has been replaced by the R or S notation, which describes the arrangement of the molecules around the chiral centre (R is for rectus, the Latin for right, and S for sinister, left).

18. R S

19. Chiral switch – drugs Esomeprazole S amlodipine Levocetrizine
Levosalbutamol
Levodopa
Escitalopram
S – warfarin

20. Clinical scenario in anesthesia

21. Intravenous general anaesthetics
Etomidate is unique among intravenous anaesthetics because it is administered as an optically pure R(+) isomer, which is the active component.
S(-) thiopentone was found to be about twofold more potent than the R(+) thiopentone in the potentiation of gamma-amino butyric acid (GABA) at GABA A receptors

22. Ketamine
The single S(+) enantiomer of ketamine is two to three times as potent as the R(-) enantiomer and produces less cardiac depression.
The S(+) enantiomer does not block myocardial ischaemic preconditioning and causes less intense hallucinations. 

23. Optical isomerism of ketamine

24. Dexmed
Dexmedetomidine, an imidazole compound, is the pharmacologically active dextro-enantiomer of medetomidine that displays specific and selective alpha 2-adrenoceptor agonism.
The central alpha 2-adrenoceptor agonist activity is specific to the dextro enantiomer of medetomidine, thus again utilizing chiral principle

25. Inhalational agents

27. Atracurium has four chiral centres in its bis-benzylisoquinolinium structure and the marketed product is a mixture of 10 optical and geometric isomers:
three cis–cis, four cis–trans and three trans–trans isomers.
Cisatracurium is R-R′ optical isomer of the cis–cis configuration

28. Gantacurium is a new neuromuscular agent which is metabolized by cysteine
But L cysteine hopes to become a promising reversal agent in the future

29. Local anesthetics
Laevobupivacaine appears to cause less myocardial depression than both bupivacaine and ropivacaine, despite being in higher concentrations.
Electrophysiological studies have been carried out which demonstrate that blockade of the inactive Na+ channels is stereoselective, with the D isomer being more potent and faster than the L isomer.
As this includes the cardiac fibres, it explains the higher cardiotoxicity associated with the D isomer. 

30. N

31. Ropi is itself Less motor blockade Less potent Less cardiotoxic
Pediatric use

35. General points Agonist – antagonist Effects – side effects
Metabolism and pharmacokinetics
the (S, (-)-isomers are more potent but have shorter terminal half lives

36. Why we need switches ??
Less complex, more selective pharmacodynamic profile
Potential for an improved therapeutic index
Less complex pharmacokinetic profile
Reduced potential for complex drug interactions
Less complex relationship between plasma concentration and effect

37. They don’t have chiral centres
sevoflurane
propofol

38. Summary Isomerism Types Examples Why Clinical uses
This is the response to the class