Local Anaesthetics

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Chapter: Medicinal Chemistry : Local Anaesthetics

Local anaesthetics are drugs that when applied directly to the peripheral nervous tissue blocks nerve conduction and abolish all the sensations in that part supplied by the nerve.

Local Anaesthetics


Local anaesthetics are drugs that when applied directly to the peripheral nervous tissue blocks nerve conduction and abolish all the sensations in that part supplied by the nerve. They are generally applied to the somatic nerves and capable of cutting on axons, cell body, dendrites, and synapses.

These are used in dentistry, in ophthalmology, in minor surgical operations, including endoscopy, and for relieving pain in certain medical conditions such as tumours growing in the spine. Local anaesthetics are also used topically for the temporary relief of pain from insect bites, burns, and other surface wounds.

Most local anaesthetic agents are weak bases, consisting of lipophilic groups connected by an intermediate chain to the tertiary amino groups. For therapeutic application, they are usually made available as salts to increase the solubility and the stability in the body. They exist either as the unchanged base or as a cation.

The clinically used local anaesthetics have minimal local irritant action and block sensory nerve endings, nerve trunks, neuromuscular junction, ganglionic synapse, and receptors that function through increased net (nerve) permeability. They also reduce the release of acetylcholine from motor nerve endings. Sensory and motor fibres are inherently and equally sensitive. The sensitivity is determined by the diameter of the fibres as well as by the fibre type. Diameters remaining the same, myelinated neurons are blocked earlier than nonmyelinated neurons. Autonomic fibres are generally more susceptible than somatic fibres. Among the somatic afferent order of blockade is pain, temperature, sense, touch and deep pressure sense, since pain is generally carried out by smaller diameter fibres than those carrying other sensations or motor impulses.

In clinical practice, a solution of local anaesthetic (except cocaine) often contains a vasoconstrictor (epinephrine, norepinephrine or phenylepinephrine). The vasoconstrictor serves dual purpose by decreasing the rate of absorption. It not only localizes the anaesthetic at the desired site, but also limits the rate at which it is absorbed into the circulation. The vasoconstrictor prolongs the action and lowers the systemic toxicity of local anaesthetics.

Mode of action: Local anaesthetics block both the generation and the conduction of the nerve impulse. The blockade probably results from the biochemical changes caused by the drug. Immediately after the nerve impulse had passed, the pores again become smaller. Sodium ions are pumped out of the fibre, at the same time potassium ions are transported into the fibre. Local anaesthetic decreases the permeability of cell membrane to sodium, thus preventing sodium depolarization.

Metabolism of local anaesthetics: Clinically available local anaesthetics are broadly divided into esters (e.g. procaine) and nonesters (e.g. lignocaine). The esters are hydrolyzed by esterases enzyme into p-amino benzoic acid and corresponding alcohols. The nonester types are primarily metabolized in the liver by CYP450, for example, lidocaine is converted primarily into 3-hydroxyl lidocaine to form 3-hydroxymono ethyl glycine-xylidine. Both may be excreted in their conjugated form. Lidocaine also metabolized into 4-hydroxy-2,6-dimethylanilide and 2-amino-3 methyl benzoic acid from the precursor metabolite 2,6xylidine. The 2,6-xylidine is also directly excreted in its conjugated form, and it is formed from mono ethyl glycine xylidine, which is an immediate metabolite of lidocaine.

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