Page 484 - Basic _ Clinical Pharmacology ( PDFDrive )

470 SECTION V Drugs That Act in the Central Nervous System

to a shorter plasma half-life (approximately 20 minutes), potentially obstetrical anesthesia where its rapid hydrolysis served to mini-
imparting a better therapeutic index with respect to systemic toxic- mize risk of systemic toxicity or fetal exposure. The unfortunate
ity. These characteristics have led to widespread popularity in dental reports of neurologic injury associated with apparent intrathecal
anesthesia, where it is generally considered to be more effective, and misplacement of large doses intended for the epidural space led
possibly safer, than lidocaine, the prior standard. Balanced against to its near abandonment. However, the frequent occurrence of
these positive attributes are concerns that development of persistent TNS with lidocaine administered as a spinal anesthetic has cre-
paresthesias, while rare, may be three times more common with artic- ated an anesthetic void that chloroprocaine appears well suited
aine. However, prilocaine has been associated with an even higher to fill. The onset and duration of action of spinal chloroprocaine
relative incidence (twice that of articaine). Importantly, these are the are even shorter than those of lidocaine, while presenting little,
only two dental anesthetics that are formulated as 4% solutions; the if any, risk of TNS. Although never exonerated with respect to
others are all marketed at lower concentrations (eg, the maximum the early neurologic injuries associated with epidural anesthesia,
concentration of lidocaine used for dental anesthesia is 2%), and it it is now appreciated that high doses of any local anesthetic are
is well established that anesthetic neurotoxicity is, to some extent, capable of inducing neurotoxic injury. A formulation is now
concentration-dependent. Thus, it is quite possible that enhanced risk marketed in Europe specifically for spinal anesthesia, and there
derives from the formulation rather than from an intrinsic property of is considerable off-label use of a preservative-free solution in
the anesthetic. In a recent survey of US and Canadian dental schools, the USA. Nonetheless, documented use as a spinal anesthetic is
over half of respondents indicated that 4% articaine is no longer used relatively limited, and additional experience will be required to
for mandibular nerve block. firmly establish safety. In addition to chloroprocaine’s emerging
use for spinal anesthesia, it still finds some current use as an epi-
dural anesthetic, particularly in circumstances where there is an
BENZOCAINE indwelling catheter and the need for quick attainment of surgi-

cal anesthesia, such as caesarian section for a laboring parturient
As previously noted, benzocaine’s pronounced lipophilicity has with a compromised fetus.
relegated its application to topical anesthesia. However, despite over
a century of use for this purpose, its popularity has recently dimin-
ished owing to increasing concerns regarding its potential to induce COCAINE
methemoglobinemia. Elevated levels can be due to inborn errors or
can occur with exposure to an oxidizing agent, and such is the case Current clinical use of cocaine is largely restricted to topical
with significant exposure to benzocaine (or nitrites, see Chapter 12). anesthesia for ear, nose, and throat procedures, where its intense
Because methemoglobin does not transport oxygen, elevated levels vasoconstriction can serve to reduce bleeding. Even here, use has
pose serious risk, with severity obviously paralleling blood levels. diminished in favor of other anesthetics combined with vaso-
constrictors because of concerns about systemic toxicity, as well
BUPIVACAINE as the inconvenience of dispensing and handling this controlled
substance.
Based on concerns for cardiotoxicity, bupivacaine is often avoided for
techniques that demand high volumes of concentrated anesthetic, ETIDOCAINE
such as epidural or peripheral nerve blocks performed for surgi-
cal anesthesia. In contrast, relatively low concentrations (≤ 0.25%) Introduced along with bupivacaine, etidocaine has had limited
are frequently used to achieve prolonged peripheral anesthesia and application due to its poor block characteristics. It has a ten-
analgesia for postoperative pain control, and the drug enjoys similar dency to produce an inverse differential block (ie, compared
popularity where anesthetic infiltration is used to control pain from a with other anesthetics such as bupivacaine, it produces exces-
surgical incision. It is often the agent of choice for epidural infusions sive motor relative to sensory block), which is rarely a favorable
used for postoperative pain control and for labor analgesia. Finally, it attribute.
has a comparatively unblemished record as a spinal anesthetic, with
a relatively favorable therapeutic index with respect to neurotoxicity,
and little, if any, risk of TNS. However, spinal bupivacaine is not well LEVOBUPIVACAINE
suited for outpatient or ambulatory surgery, because its relatively long
duration of action can delay recovery, resulting in a longer stay prior As previously discussed, this S(–) enantiomer of bupivacaine is
to discharge to home. somewhat less cardiotoxic than the racemic mixture. It is also less
potent and tends to have a longer duration of action, although
the magnitude of these effects is too small to have any substantial
CHLOROPROCAINE clinical significance. Interestingly, recent work with lipid resus-
citation suggests a potential advantage of levobupivacaine over
The introduction of chloroprocaine into clinical practice in ropivacaine, as the former is more effectively sequestered into a
1951 represented a reversion to the earlier amino-ester template. so-called lipid sink, implying greater ability to reverse toxic effects
Chloroprocaine gained widespread use as an epidural agent in should they occur.