LOCAL ANAESTHESIA by Dr. Sindwa Kanyimba (BSc, MBChB, MSc) - University of Zambia School of Medicine - Neuropharmacology-unza

LOCAL ANAESTHESIA Dr Sindwa Kanyimba (BSc, MBChB, MSc) University of Zambia School of Medicine MB ChB Program PGY 4110 Neuropharmacology Introduction Local anaesthetics are agents that produce localized, reversible block to nerve conduction. They are administered locally. Mechanism of Action Local anesthetics produce anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves This is achieved by anesthetics reversibly binding to and inactivating sodium channels. Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. When a nerve loses depolarization and capacity to propagate an impulse, the individual loses sensation in the area supplied by the nerve Physiologic activity of local anaesthetics Physiologic activity of local anesthetics is a function of their: lipid solubility diffusibility affinity for protein binding percent ionization at physiologic pH vasodilating properties Lipid solubility: potency is directly related to lipid solubility, because 90% of the nerve cell membrane is composed of lipid. Increased lipid solubility leads to faster nerve penetration and blockade of sodium channels. Diffusibility of the local anesthetic through tissue other than nerve tissue influences the speed of action onset Protein binding: the more firmly the local anesthetic binds to the protein of the sodium channel, the longer the duration of action Physiologic activity of local anaesthetics …. cont’d Percent ionization The speed of onset of action increases with the proportion of non-ionized form because the non-ionized portion is the form that is capable of diffusing across nerve membranes and blocking sodium channels A decrease in pH shifts equilibrium toward the ionized form, delaying onset of action. This explains why local anesthetics are slower in onset of action and less effective in the presence of inflammation, which creates a more acidic environment with lower pH. Addition of sodium bicarbonate is used clinically to increase the pH of local anesthetic solutions thereby enhancing onset of action Termination of local anaesthetic effects Local anaesthetic effects are terminated by uptake into the systemic circulation The rate of systemic absorption is determined by: pharmacokinetic properties of the drug vascularity of the area concentration of the solution rate of injection Use of vasoconstrictors with local anaesthetics All local anesthetics, with the exception of cocaine, are vasodilators Vasodilatation occurs via direct relaxation of peripheral arteriolar smooth muscle fibers Greater vasodilator activity of a local anesthetic leads to faster absorption of the local anaesthetic into the blood stream and thus shorter duration of action To counteract this vasodilatation, epinephrine (which induces vasoconstriction) is often included in local anesthetic solutions to: To delay systemic absorption hence prolonging the local block To limit toxicity (allows administration of lower doses) Vasoconstrictors should be avoided in areas supplied by end arteries e.g. toes, fingers, nose, ears, penis (gangrene may occur) Types of local anaesthetics Esters E.g. cocaine, procaine, amethocaine, tetracaine and chloroprocaine They are metabolized in plasma by esterases Most likely to cause allergic reactions Amides E.g. lignocaine, bupivacaine, prilocaine, cinchocaine, mepivacaine, etidocaine Metabolised in the liver by cytochrome P450 enzymes Adverse effects of local anaesthetics Allergic reactions (ester-type local anaesthetics) Adverse effects on systemic absorption: myocardial depression vasodilatation hypotension CNS excitation (restlessness, tremors, fits) followed by CNS depression depress uterine contractility can cross the placenta and cause neonatal bradycardia and CNS depression Techniques of local anaesthesia (LA) Surface anaesthesia: LA is applied to the skin or mucous membranes (e.g. lignocaine, cocaine and tetracaine). Used to relieve pain and itching from various causes Infiltration: LA is injected directly into the immediate area of surgery (e.g. procaine, lignocaine and bupivacaine) Nerve block anaesthesia: LA injection is made into or near the nerves that supply the surgical field (e.g. lignocaine, procaine, prilocaine and mepivacaine) Techniques of local anaesthesia …. cont’d Intravenous regional anaesthesia: LA is injected into a distal vein of an arm or leg to anaesthetize the limb (e.g. prilocaine and lignocaine) Epidural anaesthesia: LA is injected into the epidural space and it diffuses into the subarachnoid space producing anaesthesia of nerve roots and spinal cord (e.g. lignocaine and bupivacaine) Spinal anaesthesia: LA is injected into the subarachnoid space to produce anaesthesia of the nerve roots and spinal cord (e.g. lignocaine and tetracaine) Choice of local anaesthetic …