4. Bupivacaine, Ropivacaine, Lidocaine and Prilocaine & Adjuncts

four are local anaesthetics which produce a reversible block of neuronal transmission, and which are synthetic derivatives of cocaine. They each possess the same three essential functional units, namely a hydrophilic chain joined by an amide linkage to a lipophilic aromatic moiety

: The parent compound of ropivacaine and bupivacaine is MEpivacaine, which has a single MEthyl group attached to the tertiary amine. BUpivacaine is identical apart from a BUtyl (C4H9) side chain. The structure of ROPivacaine differs only in its shorter pPROyl (C3H7) substituent on the piperidine nitrogen atom. Prilocaine has a different structure in the lipophilic moiety with a single methyl group on the aromatic ring (unlike the 2,6-xylidine ring in the other amides)

: Chloroprocaine > Lidocaine/Prilocaine > Bupivacaine/ Ropivacaine.) latency of local anaesthetics is related to their pKa

Potency: this is determined primarily by lipid solubility, which is increased by the substitution of longer side chains. Bupivacaine’s longer butyl (C4H9) side chain increases at least threefold its lipid solubility in comparison with ropivicaine with its shorter propyl (C3H7) substituent

this is also affected by structural differences in the molecule. The affinity of local anaesthetics for the sodium channel is related to the length of the aliphatic chains. Duration: bupivacaine 175’ > ropivacaine 150’ > lidocaine/prilocaine 100’.)

The cardiovascular and CNS toxicity of bupivacaine, however, is a function of the R (+) enantiomer. The S (−) enantiomer has less affinity for, and dissociates faster from, myocardial sodium channels. This is now available as levobupivacaine (Chirocaine), and would appear to be no more dangerous than ropivacaine. (Toxicity: bupivacaine > levobupivacaine > ropivacaine > lidocaine > prilocaine.)

Prilocaine is both less lipid-soluble and more weakly protein-bound than lidocaine, yet plasma concentrations are lower even when the same dose is given by the same route, and it is some 40% less toxic toluidine ring is more rapidly metabolized to ortho (o)-toluidine ortho-toluidine metabolite causes methaemoglobinaemia by oxidizing the ferrous iron in haemoglobin to the ferric state methaemoglobin crosses the placenta, this further compromises oxygen delivery to the fetus, and so prilocaine is generally avoided in pregnancy.

capacity of a local anaesthetic to block sensory nerves preferentially while sparing motor nerves continuous epidurals for labour and for surgical analgesia. It is well known that this group of local anaesthetics demonstrates preferential sensory block; the purported superiority of ropivacaine is illusory and is based on the fact that it is simply a less potent drug

which helps to explain true sensory– motor dissociation Drug entry into the sodium channels occurs when the channel is open during the period of membrane depolarization pain and sensory fibres conduct at high frequency, whereas motor impulses are at a lower frequency. sodium channels are open more times per second Lidocaine, prilocaine, bupivacaine and ropivacaine all produce a more rapid and denser block in these sensory nerves of higher frequency

: amide local anaesthetics bind mainly to α1-acid glycoprotein (highaffinity, low-capacity binding site), and to albumin (low-affinity, high-capacity). They undergo aromatic hydroxylation, amide hydrolysis and N-dealkylation (phase 1 reactions) in the liver. There is some suggestion of extrahepatic pulmonary metabolism (uptake and sequestration is greatest with prilocaine).

Both onset and duration of action are related to the lipid solubility of the drug. Duration: Morphine has low lipid solubility, = 18 hours whereas that of fentanyl is high, = 2–4 hours

lipophilic drugs cross rapidly into the cord, while hydrophilic agents remain partly within the CSF, in which they may be carried rostrally to act on higher centres. delayed respiratory depression may be caused morphine than with other drugs, and is better monitored by sedation scoring than respiratory rate complications of spinal opioids include nausea, vomiting, urinary retention and pruritus A logical alternative treatment, which can be useful for pruritus, is intravenous nalbuphine

the specific receptors that are located in the dorsal horn of the spinal cord They are most densely concentrated in the substantia gelatinosa, which comprises lamina II and part of lamina III of the laminae of Rexed 75% of the receptors are pre-synaptic, and they mediate inhibition of the release of nociceptive transmitters such as substance P

evidence that the addition of vasoconstrictors does not have a consistent action; the addition of adrenaline prolongs the action of intrathecal amethocaine, for example, but has little effect when added to bupivacaine or lignocaine.

Pre-synaptic activation inhibits noradrenaline release from the nerve terminal and thereby influences descending pathways Clonidine doubles the duration of action of intrathecal bupivacaine, prolonging both sensory and motor block hypotension, dry mouth and sedation. Dexmedetomidine is both more potent and more α2-selective.