Local anaesthetic agents have varying onset times, duration of action and ability to penetrate tissue. Chemically they are separated into esters (cocaine, procaine, amethocaine) and amides (lidocaine, prilocaine, bupivacaine), which is relevant to their metabolism and tendency to toxicity. Esters are rapidly metabolized by serum and liver cholinesterase and therefore metabolism is retarded by low enzyme levels such as pregnancy or liver disease. Amides are metabolized by liver microsomal enzymes, which may be less effective when hepatic function or blood flow are reduced.

Local anaesthetics work by reversibly blocking conduction along nerve fibres through binding to voltage-gated sodium channels in the neuronal membrane. This prevents sodium ion entry during depolarization, which in turn prevents the propagation of the action potential. The membrane in effect becomes stabilized. Consequently, the response to painful stimuli is not effected and pain is not sensed centrally.

Local anaesthetics are weak bases and are most efficacious in alkaline conditions, whereby the un-ionized form crosses the neuronal membrane. Conversely, infected or inflamed tissues have an acidic environment, which reduces the action of local anaesthetics. Furthermore, the increased vascularity of these environments gives rise to an increased risk of systemic absorption and subsequent side-effects. Local anaesthetics affect the smaller nerves such as the autonomic before the medium-sized sensory and large motor nerves. They are more effective at higher concentrations, having a shorter onset and longer duration. The duration of local anaesthetics is prolonged when combined with vasoconstrictors such as weak epinephrine solutions (e.g. 1 in 200, 000).