Cocaine was the first drug to be used as a local anaesthetic. It was introduced into medicine in 1884 by Koller. Other drugs soon followed, for example, ethyl chloride spray, tropocaine, eugenol (oil of cloves) and Nupercaine. A wide range of uses for local anaesthetics soon developed and the term 'regional anaesthesia' was first used by Cushing in 1901 to describe pain relief by nerve blockade. Local anaesthetic drugs are water soluble salts of lipid soluble alkaloids. Each molecule is composed of an aromatic portion, intermediate chain and an amide portion. The portions are joined by either amide or ester linkages. Ester-linked drugs are hydrolysed in the plasma by plasma cholinesterase and their half-life varies from one to eight minutes. Amide-linked drugs are degraded by oxidative dealkylation in the liver. The half-life of these drugs varies from 1.5 to more than three hours. The addition of a vasoconstrictor, such as adrenaline, will prolong the duration of action of both the amide- and ester-linked drugs. Degradation of the amide-linked drugs depends on factors such as hepatic blood flow and liver conditions, such as cirrhosis, and congestive cardiac failure. Anaphylactic reactions are more common with ester-linked drugs than amide-linked drugs. The drugs are usually available for injection as hydrochlorides in a salt solution with small amounts of fungicides or preservatives added to give stability.