Local anesthetics

Local anesthetics block nerve conduction of sensory impulses and, in higher concentrations, motor impulses from the periphery to the CNS. Delivery techniques include topical administration, infiltration, peripheral nerve blocks, and neuraxial (spinal, epidural, or caudal) blocks. Small, unmyelinated nerve fibers for pain, temperature, and autonomic activity are most sensitive.
Structure
Local anesthetics all include a lipophilic group joined by an amide or ester linkage to a carbon chain, which, in turn, joined to a hydrophilic group.

Metabolism
Biotransformation of amides occurs primarily in the liver. Prilocaine, a dental anesthetic, is also metabolized in the plasma and kidney, and one of its metabolites may lead to methemoglobinemia. Esters metabolized by plasma cholinesterase(pseudocholinesterase).

Onset and duration of action
The onset and duration of action of local anesthetics influenced by several factors including
1-Tissue pH,
2- Nerve morphology,
3- Concentration,
4-pKa, and
5- Lipid solubility of the drug.
Of these, the pH of the tissue and pKa are most important. At physiologic pH, these compounds are charged. The ionized form interacts with the protein receptor of the Na+ channel to inhibit its function and achieve local anesthesia. The pH may drop in infected sites, causing onset to be delayed or even prevented. Within limits, higher concentration and greater lipid solubility improve onset somewhat. Duration of action depends on the length of time the drug can stay near the nerve