DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

576 amount of cream that can be applied and area of skin covered.
These mixtures must not be used on mucous membranes or
abraded skin, as rapid absorption across these surfaces may result
in systemic toxicity.
SECTION II
NEUROPHARMACOLOGY
Infiltration Anesthesia
Infiltration anesthesia is the injection of local anesthetic directly into
tissue without taking into consideration the course of cutaneous
nerves. Infiltration anesthesia can be so superficial as to include
only the skin. It also can include deeper structures, including intraabdominal
organs, when these too are infiltrated.
The duration of infiltration anesthesia can be approximately
doubled by the addition of epinephrine (5 μg/mL) to the injection
solution; epinephrine also decreases peak concentrations of local
anesthetics in blood. Epinephrine-containing solutions should not,
however, be injected into tissues supplied by end arteries—for example,
fingers and toes, ears, the nose, and the penis. The resulting
vasoconstriction may cause gangrene. For the same reason, epinephrine
should be avoided in solutions injected intracutaneously. Since
epinephrine also is absorbed into the circulation, its use should be
avoided in those for whom adrenergic stimulation is undesirable.
The local anesthetics used most frequently for infiltration
anesthesia are lidocaine (0.5-1%), procaine (0.5-1%), and bupivacaine
(0.125-0.25%). When used without epinephrine, up to 4.5 mg/kg
of lidocaine, 7 mg/kg of procaine, or 2 mg/kg of bupivacaine can be
employed in adults. When epinephrine is added, these amounts can
be increased by one-third.
The advantage of infiltration anesthesia and other regional
anesthetic techniques is that it can provide satisfactory anesthesia
without disrupting normal bodily functions. The chief disadvantage
of infiltration anesthesia is that relatively large amounts of drug must
be used to anesthetize relatively small areas. This is no problem with
minor surgery. When major surgery is performed, however, the
amount of local anesthetic that is required makes systemic toxic
reactions likely. The amount of anesthetic required to anesthetize an
area can be reduced significantly and the duration of anesthesia
increased markedly by specifically blocking the nerves that innervate
the area of interest. This can be done at one of several levels: subcutaneously,
at major nerves, or at the level of the spinal roots.
Field Block Anesthesia
Field block anesthesia is produced by subcutaneous injection of a
solution of local anesthetic in order to anesthetize the region distal
to the injection. For example, subcutaneous infiltration of the proximal
portion of the volar surface of the forearm results in an extensive
area of cutaneous anesthesia that starts 2-3 cm distal to the site of
injection. The same principle can be applied with particular benefit to
the scalp, the anterior abdominal wall, and the lower extremity.
The drugs, concentrations, and doses recommended are the
same as for infiltration anesthesia. The advantage of field block anesthesia
is that less drug can be used to provide a greater area of anesthesia
than when infiltration anesthesia is used. Knowledge of the
relevant neuroanatomy obviously is essential for successful field
block anesthesia.
Nerve Block Anesthesia
Injection of a solution of a local anesthetic into or about individual
peripheral nerves or nerve plexuses produces even greater areas of
anesthesia than do the techniques already described. Blockade of
mixed peripheral nerves and nerve plexuses also usually anesthetizes
somatic motor nerves, producing skeletal muscle relaxation, which
is essential for some surgical procedures. The areas of sensory and
motor block usually start several centimeters distal to the site of
injection. Brachial plexus blocks are particularly useful for procedures
on the upper extremity and shoulder. Intercostal nerve blocks
are effective for anesthesia and relaxation of the anterior abdominal
wall. Cervical plexus block is appropriate for surgery of the neck.
Sciatic and femoral nerve blocks are useful for surgery distal to the
knee. Other useful nerve blocks prior to surgical procedures include
blocks of individual nerves at the wrist and at the ankle, blocks of
individual nerves such as the median or ulnar at the elbow, and
blocks of sensory cranial nerves.
There are four major determinants of the onset of sensory
anesthesia following injection near a nerve:
• proximity of the injection to the nerve
• concentration and volume of drug
• degree of ionization of the drug
• time
Local anesthetic is never intentionally injected into the
nerve, as this would be painful and could cause nerve damage.
Instead, the anesthetic agent is deposited as close to the nerve as
possible. Thus the local anesthetic must diffuse from the site of
injection into the nerve, where it acts. The rate of diffusion is
determined chiefly by the concentration of the drug, its degree of
ionization (ionized local anesthetic diffuses more slowly), its
hydrophobicity, and the physical characteristics of the tissue surrounding
the nerve. Higher concentrations of local anesthetic will
provide a more rapid onset of peripheral nerve block. The utility
of higher concentrations, however, is limited by systemic toxicity
and by direct neural toxicity of concentrated local anesthetic solutions.
For a given concentration, local anesthetics with lower pK a
values tend to have a more rapid onset of action because more
drug is uncharged at neutral pH. For example, the onset of action of
lidocaine occurs in ~3 minutes; 35% of lidocaine is in the basic
form at pH 7.4. In contrast, the onset of action of bupivacaine
requires ~15 minutes; only 5-10% of bupivacaine is uncharged at
this pH. Increased hydrophobicity might be expected to speed
onset by increased penetration into nerve tissue. However, it also
will increase binding in tissue lipids. Furthermore, the more
hydrophobic local anesthetics also are more potent (and toxic) and
thus must be used at lower concentrations, decreasing the concentration
gradient for diffusion. Tissue factors also play a role in
determining the rate of onset of anesthetic effects. The amount of
connective tissue that must be penetrated can be significant in a
nerve plexus compared to isolated nerves and can slow or even
prevent adequate diffusion of local anesthetic to the nerve fibers.
Duration of nerve block anesthesia depends on the physical
characteristics of the local anesthetic used and the presence or
absence of vasoconstrictors. Especially important physical characteristics
are lipid solubility and protein binding. Local anesthetics
can be broadly divided into three categories:
• those with a short (20-45 minutes) duration of action in mixed
peripheral nerves, such as procaine
• those with an intermediate (60-120 minutes) duration of action,
such as lidocaine and mepivacaine