· Definitions
· Examples
Structural isomerism |
· Same chemical formula, different bond structure · Different effects: dihydrocodeine (opioid) and dobutamine (catecholamine) · Similar effect: isoflurane and enflurane – volatile anaesthetics |
Tautomerism |
· Change in structure dependent upon physical environment |
Stereoisomerism |
· Same chemical formula, same bond structure, different 3D orientation |
-Geometric stereoisomerism |
· Different pairs of chemical groups attached to two carbons joined by a double bond or ring structure · Cis = same direction, trans = opposite direction |
-Optical stereoisomerism |
· Four different groups attached to a chiral (Gk. hand) centre, usually a carbon or quaternary nitrogen group · Four groups point to the vertices of a tetrahedron · Two mirror image conformations, not super-imposable · Laevo/dextro: enantiomer rotates plane polarized light left/right · Rectus/sinister: smallest group ‘behind the page’, three largest groups of the enantiomer arranged in descending order clockwise/anticlockwise |
-Diastereoisomerism |
· Multiple chiral centres |
|
Isoflurane |
Enflurane |
Molecular weight |
185 |
185 |
Boiling point |
49 |
57 |
Saturated vapour pressure |
238 |
172 |
MAC |
1.2% |
1.7% |
Blood:gas partition coefficient |
1.4 |
1.8 |
Fat:blood partition coefficient |
45 |
? |
Oil:gas partition coefficient |
98 |
98 |
% metabolised |
0.2 |
2 |
Smell |
Irritant |
Sweet |
Analgesic |
No |
Yes |
Epileptogenic |
No |
Yes |
Renal failure |
No |
Yes |
Midazolam |
· Ampoule: pH<4 -> open ring, water soluble, no carrier needed · Blood: pH >4 -> closed ring lipid soluble, crosses blood-brain barrier (BBB) |
Thiopentone |
· Ampoule: ↑pH (11)-> water soluble enol · Blood: ↓pH 7.4 -> lipid soluble keto -> crosses BBB |
Geometric |
e.g. mivacurium · Cis-cis 6% (10% potency of others, non-enzymatic metabolism, t1/2 10x others) · Cis-trans 36% · Trans-trans 58% |
Optical |
Laevo/dextro: · e.g. D-glucose metabolized, L-glucose not (i.e. dextrose) · e.g. L-bupivacaine ↑potent, ↓toxic (available enantiopure) · e.g. +tramadol mu agonist, 5-HT reuptake inhibition; -tramadol NAd reuptake inhibition · e.g. L-methadone opioid agonist, D-methadone NMDA antagonist Rectus/sinister: · e.g. S-ketamine ↑potency, ↓hallucinogen, ↓CVS toxicity; (available enantiopure) · e.g. R-etomidate 10x ↑potent (only available enantiopure) |
Diastereoisomerism |
· e.g. cisatracurium = 1R-cis,1R’-cis-atracurium · 15% of atracurium, 50% of its activity · Atracurium has 4 chiral centres; n2 = 16 conformations but only 10 unique · Cisatracurium: ↑potency, ↓histamine release, ↑Hoffman elimination, ↓ester hydrolysis |
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