Local anaesthetics: properties

Local anaesthetics: properties

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A local anaesthetic molecule comprises a lipophilic head, a hydrophilic tail, and a linking intermediate chain. The intermediate chain can be an ester (aminoester group) or an amide (aminoamide group). Aminoester local anaesthetics are more water soluble, and are primarily metabolised in plasma by pseudocholinesterases. Aminoamide local anaesthetics are less water soluble, and are primarily metabolised in the liver by de-ethylation. See Table 1.7 for characteristics of local anaesthetic drugs.

Efficacy of a particular drug is determined by its concentration at the site of action. This depends on the dose and concentration injected, diffusion to the relevant site if this is distant from the injection point, and on removal by the circulation, which in turn depends on the vascularity of the tissue. Increased lipid solubility of the local anaesthetic enhances absorption. Increased ionisation, which depends on the pKa of the drug and the pH at the site, decreases absorption (see Table 1.7).

Systemic absorption can be reduced by co-administration with a vasoconstrictor such as adrenaline, which prolongs and intensifies the local anaesthetic action, reduces surgical bleeding, and lowers peak blood concentrations of the local anaesthetic and the risk of systemic toxicity. A local anaesthetic solution with 1:200 000 adrenaline (5 micrograms/mL) is often used. Adrenaline is contraindicated in the presence of ischaemic heart disease, ventricular arrhythmias or uncontrolled hypertension, and for digital or penile nerve blocks, and intravenous block.

The uses of the different local anaesthetic solutions are summarised in Table 1.8.

Characteristics of local anaesthetics (Table 1.7)

Drug	pKa	Onset	Duration (hours) [NB1]	Maximum single adult dose [NB2]	pH of solution [NB3]	Protein binding (%)
Aminoamides
lignocaine	7.9	fast	0.5 to 2	3 mg/kg; 7 mg/kg (with adrenaline)	6.5	65
prilocaine	7.9	fast	1 to 3	6 mg/kg; 8 mg/kg (with adrenaline)	5.0 to 7.0	55
bupivacaine	8.1	intermediate to slow	4 to 12	1.5 to 2 mg/kg 2 to 3 mg/kg (with adrenaline)	4.0 to 6.5	95
levobupivacaine	8.1	intermediate to slow	4 to 12	1.5 to 2 mg/kg	4.0 to 6.5	95
ropivacaine	8.1	intermediate to slow	3 to 6	300 mg (major nerve block)	4 to 6	94
Aminoesters
procaine	8.9	slow	0.5 to 1.5	8 mg/kg	5 to 6.5	6
amethocaine (tetracaine) [NB4]	–	fast	at least 15 minutes	single dose	4.5 to 6.5	-
NB1: variable, dependent upon dose and route of administration NB2: variable, dependent upon route of administration NB3: pH lower by 1.0 to 1.5 units for adrenaline-containing solutions NB4: characteristics apply to topical use in ophthalmic procedures. See Use of local anaesthetics in children regarding its use as a topical local anaesthetic in children