Local Anaesthetics: SAR and Techniques

Local Anaesthetics: SAR and Techniques

1. Definition & overview

• Local anaesthetics (LAs) are drugs that, on topical application or local injection, cause reversible loss of sensory perception (especially pain) in a restricted area of the body, by blocking generation and conduction of the nerve impulse — without causing any structural nerve damage (KDT 8e Ch.26, p.386).
• They can act on any part of the neurone and on every type of nerve fibre; in contact with a nerve trunk an LA produces both sensory and motor paralysis, plus loss of autonomic control, in the area innervated (G&G 14e Ch.25, p.489; KDT 8e Ch.26, p.386).
• At clinically relevant concentrations the effect is fully reversible, with recovery of nerve function and no evidence of damage to fibres or cells in most applications (G&G 14e Ch.25, p.489).
• Distinguishing feature vs. analgesics: LAs provide complete loss of all sensory modalities, not merely analgesia; the drug is delivered directly to the target organ, and the systemic circulation serves only to diminish or terminate the effect (Katzung 16e Ch.26, p.484).
• Local vs. general anaesthesia — site of action peripheral nerves vs. CNS; restricted area vs. whole body; consciousness unaltered vs. lost; physiological trespass low vs. high; safer in poor-health patients; preferred for minor surgery but cannot substitute for major surgery; not usable in the non-cooperative patient (KDT 8e Ch.26, Table 26.1, p.386).
• Historical anchor — cocaine (from Erythroxylon coca) was the first LA; isolated by Niemann (1860), introduced clinically by Carl Koller (1884) for corneal/ophthalmic anaesthesia; Halstead popularised infiltration and conduction block; the search for safer synthetic substitutes yielded procaine (Einhorn, 1905), the prototype ester LA for nearly half a century (G&G 14e Ch.25, p.489; KDT 8e Ch.26, p.391; Katzung 16e Ch.26, p.485).
• Non-pharmacological local anaesthesia can also be produced by cooling (ice, CO₂ snow, ethylchloride spray) (KDT 8e Ch.26, p.386).
• Several non-anaesthetic drugs (propranolol, chlorpromazine, H₁-antihistaminics, quinine) have significant LA activity but are not used for this purpose due to local irritancy or systemic effects (KDT 8e Ch.26, p.386).