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| | Anesthetics, Local Basic information |
| | Anesthetics, Local Chemical Properties |
| | Anesthetics, Local Usage And Synthesis |
| Chemical Properties | The basic components in the structure of local anesthetics
are the lipophilic aromatic portion (a benzene
ring), an intermediate chain, and the hydrophilic amine
portion.The intermediate chain has either an
ester linkage from the combination of an aromatic acid
and an amino alcohol or an amide linkage from the
combination of an aromatic amine and an amino acid.
The commonly used local anesthetics can be classified
as esters or amides based on the structure of this intermediate
chain. | | Biological Functions | An important property of the ideal local anesthetic is
low systemic toxicity at an effective concentration.
Onset of action should be quick, and duration of action
should be sufficient to allow time for the surgical procedure.
The local anesthetic should be soluble in water and
stable in solution. It should not deteriorate by the heat
of sterilization, and it should be effective both when injected
into tissue and when applied topically to mucous
membranes. Its effects should be completely reversible.
Although the characteristics of an ideal local anesthetic
are easily identifiable, synthesis of a compound
possessing all these properties has not been accomplished.
The compounds discussed in the following sections
fall short of the ideal in at least one aspect.
However, the judicious choice of a particular agent for
a particular need will permit the practitioner to employ
local anesthesia effectively and safely. | | Mechanism of action | The application of a local anesthetic to a nerve that is
actively conducting impulses will inhibit the inward migration
of Na.This elevates the threshold for electrical
excitation, reduces the rate of rise of the action potential,
slows the propagation of the impulse, and if the
drug concentration is sufficiently high, completely
blocks conduction. The local anesthetics interfere with
the process fundamental to the generation of the action
potential, namely, the large, transient voltage-dependent
rise in the permeability of the membrane to Na.
While the physiological basis for the local anesthetic
action is known, the precise molecular nature of the
process is not completely clear. Almost all local anesthetics
can exist as either the uncharged base or as a
cation. The uncharged base is important for adequate
penetration to the site of action, and the charged form
of the molecule is required at the site of action. The
cation forms of local anesthetics appear to be required
for binding to specific sites in or near the Na channels.
The presence of the local anesthetic at these sites interferes
with the normal passage of Na through the cell
membrane by stopping a conformational change in the
subunits of the voltage-gated Na channel.
Studies suggest that the receptor for the local anesthetic
is near the inner (axoplasmic) surface of the cell
membrane, because quaternary analogues of local anesthetics
are quite effective when applied to the inside of
the axonal membrane but are inactive when placed on
the outside of the membrane. These permanently
charged molecules cannot penetrate to the receptor
sites.
Nerves that are rapidly depolarizing are inherently
particularly susceptible to the effects of local anesthetics.
This is termed frequency-dependent blockade and is
thought to occur because the local anesthetics get to their receptor sites only when the Na channel is open
(depolarizing). |
| | Anesthetics, Local Preparation Products And Raw materials |
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