Page 473 - Basic _ Clinical Pharmacology ( PDFDrive )

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Local Anesthetics

Kenneth Drasner, MD

C ASE STUD Y

A 67-year-old woman is scheduled for elective total knee complications might arise from their use? What anesthet-
arthroplasty. What local anesthetic agents would be most ics would be most appropriate for providing postoperative
appropriate if surgical anesthesia were to be administered analgesia via an indwelling epidural or peripheral nerve
using a spinal or an epidural technique, and what potential catheter?

Simply stated, local anesthesia refers to loss of sensation in a ■ BASIC PHARMACOLOGY OF
limited region of the body. This is accomplished by disrup-
tion of afferent neural traffic via inhibition of impulse genera- LOCAL ANESTHETICS
tion or propagation. Such blockade may bring with it other
physiologic changes such as muscle paralysis and suppression Chemistry
of somatic or visceral reflexes, and these effects might be Most local anesthetic agents consist of a lipophilic group (eg, an
desirable or undesirable depending on the particular circum- aromatic ring) connected by an intermediate chain via an ester or
stances. Nonetheless, in most cases, it is the loss of sensation, amide to an ionizable group (eg, a tertiary amine) (Table 26–1).
or at least the achievement of localized analgesia, that is the In addition to the general physical properties of the molecules,
primary goal. specific stereochemical configurations are associated with dif-
Although local anesthetics are often used as analgesics, it ferences in the potency of stereoisomers (eg, levobupivacaine,
is their ability to provide complete loss of all sensory modali- ropivacaine). Because ester links are more prone to hydrolysis than
ties that is their distinguishing characteristic. The contrast amide links, esters usually have a shorter duration of action.
with general anesthesia should be obvious, but it is perhaps Local anesthetics are weak bases and are usually made avail-
worthwhile to emphasize that with local anesthesia the drug able clinically as salts to increase solubility and stability. In the
is delivered directly to the target organ, and the systemic cir- body, they exist either as the uncharged base or as a cation
culation serves only to diminish or terminate its effect. Local (see Chapter 1, Ionization of Weak Acids and Weak Bases). The
anesthesia can also be produced by various chemical or physi- relative proportions of these two forms are governed by their
cal means. However, in routine clinical practice, it is achieved pK and the pH of the body fluids according to the Henderson-
a
with a rather narrow spectrum of compounds, and recovery Hasselbalch equation, which can be expressed as:
is normally spontaneous, predictable, and without residual pK = pH – log [base]/[conjugate acid]
effects. The development of these compounds has a rich his- a
tory (see Box: Historical Development of Local Anesthesia), If the concentration of base and conjugate acid are equal, the second
punctuated by serendipitous observations, delayed starts, and portion of the right side of the equation drops out, as log 1 = 0, leaving:
an evolution driven more by concerns for safety than improve- pK = pH (when base concentration = conjugate acid
a
ments in efficacy. concentration)

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