LOCAL ANESTHETICS

Local anesthetic produces the loss of sensation in a body part without the loss of consciousness
or the impairment of central control of vital functions.
CLASSIFICATION:
The local anesthetics are classified as
ESTERS
Tetracaine

AMIDES
Bupivacaine

Cocaine

Ropivacaine

Procaine

Lidocaine (xylocaine)

Benzocaine

Mepivacaine

DIFFRENCE BETWEEN ESTERS AND AMIDES:

Most local anesthetic agents consist of a lipophilic group (eg, an aromatic ring)
connected by an intermediate chain via an ester or amide to an ionizable group (eg, a

tertiary amine).
Ester links are more prone to hydrolysis than amide links, esters usually have a shorter

duration of action.
The local anesthetics are converted to more water-soluble metabolites in the liver (amide
type) or in plasma (ester type), which are excreted in the urine

MEGHANISM OF ACTION:
Local anesthetics block nerve conduction of sensory impulses and, in higher concentrations,
motor impulses from the periphery to the CNS. Na+ ion channels are blocked to prevent the
transient increase in permeability of the nerve membrane to Na+ that is required for an action
potential. When propagation of action potentials is prevented, sensation cannot be transmitted
from the source of stimulation to the brain.

PHARMACOKINETICS
ABSORPTION
Absorption of injected local anesthetic from the site of administration is determined by several
factors, including dosage, site of injection, drug-tissue binding, local tissue blood flow, use of a
vasoconstrictor (eg, epinephrine), and the physicochemical properties of the drug itself.
Application of local anesthetics to highly vascular area such as the tracheal mucosa or the tissue
surrounding intercostal nerves results in more rapid absorption and thus higher blood levels than
if the local anesthetic is injected into a poorly perfused tissue such as subcutaneous fat.
When vasoconstrictors are used with local anesthetics, the resultant reduction in blood flow
serves to reduce the rate of systemic absorption and thus diminishes peak serum levels. This
effect is generally most evident with the shorter-acting, less potent and less lipid-soluble
anesthetics
DISTRIBUTION
As local anesthetic is usually injected directly at the site of the target organ, distribution within
this compartment plays an essential role with respect to achievement of clinical effect
The peak blood levels achieved during major conduction anesthesia will be minimally affected
by the concentration of anesthetic or the speed of injection. The disposition of these agents can
be well approximated by a two compartment model.
The initial alpha phase reflects rapid distribution in blood and highly perfused organs (eg, brain,
liver heart, kidney), characterized by a steep exponential decline in concentration. This is
followed by a slower declining beta phase reflecting distribution into less well perfused tissue
(eg, muscle, gut), and may assume a nearly linear rate of decline

METABOLISM AND EXCRETION

The local anesthetics are converted to more water-soluble metabolites in the liver (amide type)
or in plasma (ester type), which are excreted in the urine.

Ester-type local anesthetics are hydrolyzed very rapidly in the blood by circulating
butyrylcholinesterase to inactive metabolites. The amide local anesthetics undergo complex
biotransformation in the liver, which includes hydroxylation and ndealkylation by liver
microsomal cytochrome p450 isozymes