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

Table 20–1
Susceptibility to Block Types of Nerve Fibers
CONDUCTION
CLINICAL
DIAMETER, VELOCITY, SENSITIVITY
CLASSIFICATION ANATOMIC LOCATION MYELIN (μm) (m/sec) FUNCTION TO BLOCK
A fibers
A α Afferent to and efferent Yes 6–22 10–85 Motor and +
A β from muscles and joints proprioception ++
A γ Efferent to muscle Yes 3–6 15–35 Muscle tone ++
spindles
A δ Sensory roots and afferent Yes 1–4 5–25 Pain, temperature, +++
peripheral nerves
touch
B fibers Preganglionic sympathetic Yes <3 3–15 Vasomotor, ++++
visceromotor,
sudomotor,
pilomotor
C fibers
Sympathetic Postganglionic sympathetic No 0.3–1.3 0.7–1.3 Vasomotor, ++++
visceromotor,
sudomotor,
pilomotor
Dorsal root Sensory roots and afferent No 0.4–1.2 0.1–2 Pain, temperature, ++++
peripheral nerves
touch
Source: Adapted from Carpenter and Mackey, 1992, with permission. http://lww.com.
species that interacts preferentially with Na + channels. The results of
experiments on anesthetized mammalian nonmyelinated fibers support
this conclusion (Ritchie and Greengard, 1966). In these experiments,
conduction could be blocked or unblocked merely by
adjusting the pH of the bathing medium to 7.2 or 9.6, respectively,
without altering the amount of anesthetic present. The primary role
of the cationic form also was demonstrated by Narahashi and
Frazier, who perfused the extracellular and axoplasmic surface of
the giant squid axon with tertiary and quaternary amine local anesthetics
and found that the quaternary amines were active (Narahashi
and Frazier, 1971). However, the unprotonated molecular forms also
possess some anesthetic activity (Butterworth and Strichartz, 1990).
Recent reports indicate that quaternary local anesthetics such as QX-
314 can gain access to the cytoplasmic surface of the nerve cell
membrane via TRPV1 channels (transient receptor potential vanilloid
subtype channels) (reviewed by Butterworth and Oxford, 2009).
TRP channels, and possibly other ion channels, appear to lose selectivity
and permit permeation of molecules like QX-314 in the face of
prolonged or intense activation.
Prolongation of Action by Vasoconstrictors. The duration
of action of a local anesthetic is proportional to the
time of contact with nerve. Consequently, maneuvers
that keep the drug at the nerve prolong the period of
anesthesia. For example, cocaine inhibits the neuronal
membrane transporters for catecholamines, thereby
potentiating the effect of NE at α adrenergic receptors
in the vasculature, resulting in vasoconstriction and
reduced cocaine absorption in vascular beds where
α adrenergic effects predominate (Chapters 8 and 12).
Ropivacaine and bupivacaine also cause vasoconstriction.
In clinical practice, a vasoconstrictor, usually epinephrine,
is often added to local anesthetics. The
vasoconstrictor performs a dual service. By decreasing
the rate of absorption, it not only localizes the anesthetic
at the desired site, but also allows the rate at
which it is destroyed in the body to keep pace with the
rate at which it is absorbed into the circulation. This
reduces its systemic toxicity. It should be noted, however,
that epinephrine also dilates skeletal muscle vascular
beds through actions at β 2
adrenergic receptors,
and therefore has the potential to increase systemic toxicity
of anesthetic deposited in muscle tissue.
Some of the vasoconstrictor agents may be absorbed systemically,
occasionally to an extent sufficient to cause untoward reactions
(see the next section). There also may be delayed wound
healing, tissue edema, or necrosis after local anesthesia. These
effects seem to occur partly because sympathomimetic amines
increase the oxygen consumption of the tissue; this, together with