Local Anesthesia Local anesthesia are drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber without affecting the degree of consciousness. Chemistry of local anestheitics All the useful local anesthetics consist of three parts- Hydrophilic amino group 2) Intermediate chain (including an ester or amide) 3) Lipophilic aromatic group

The fundamental structure may be represented by- (CH2)n N R2 Basic structure The hydrophilic group is usually a tertiary amine, but it may also be a secondary amine. The intermediate chain may be either ester (cocaine) or amide (lidocaine). The nature of this bond determines the pharmacological properties of these agents. The ester link is important because this bond is readily hydrolyzed during metabolic degradation. Due to the presence of amino nitrogen, these drugs are bases and form soluble salt with acids (pH=4.6).

Structure activity relationship of LA Hydrophobicity increases both the potency and duration of action, because hydrophobic sites decrease the rate of hydrolysis by plasma easterases and enhances the partitioning of the drug to its sites of action. The smaller and more lopophilic the molecules, the faster the rate of interaction with sodium channel receptor. Hydrophobicity also increases potential toxicity.

Mechanism of action of LA Local anesthetics prevent the generation and the conduction of the nerve impulse. Their main site of action is the cell membrane. LA block both the generation and conduction of nerve impulse by decreasing or preventing the large transient increase in the permeability of excitable membranes to Na+ that is produced by a slight depolarization of the membrane. Thus action potential can not be generated, so there is no propagation and conduction of nerve impulse. LA appear to compete with Ca+2 for a site in he nerve membrane that controls the passage of Na+. So, Na+ can not enter into the cell, as a result action potential is not generated and propagation of impulse is inhibited.

Pharmacological action of LA ON CNS: Following absorption, LA may cause stimulation of CNS, producing restlesness and tremor that may proceed to clonic convulsions. In general, more potent the anesthetics the more readily convulsions may be produced. Central stimulation is followed by depression, and death is usually caused by respiratory failure. ON CVS: After systemic absorption, LA act on the CVS. The primary site of action is the myocardium, where decrease in electrical excitability, conduction rate and force of contraction occur. In addition, most LA causes arteriolar dilatation. The cardiovascular effects are usually seen only after high systemic concentrations are attained and effects on the CNS are produced.

However, on rare occasions small amount of anesthetic employed for simple infiltration anesthesia will cause cardiovascular collapse and death. This probably results from cardiac arrest due to either an action on the pacemaker or the sudden oneset of ventricular fibrillation. ON SMOOTH MUSCLES: The local anesthetics depress contractions in the intact bowel and in strips of isolated intestine. They also relax vascular and bronchial smooth muscle, although low concentrations may initially produce contractions.