Local anesthetics

History: For centuries, the Peruvian people have appreciated the pharmacologic actions
of the leaves of the Erythroxylon coca, a shrub growing high in the Andes mountains
!hewing or suc"ing these leaves produces a sense of well#being $he plant ash releases
an al"aloid in a form that can be absorbed across mucous membranes $his al"aloid is
more commonly "nown today as cocaine $he pure al"aloid of cocaine was isolated in
%&&', and its pharmacodynamic properties were further investigated (n %&&), cocaine
was used clinically as a local anesthetic in ophthalmology, dentistry, and surgery (n %*'+,
the first synthetic local anesthetic, procaine, was developed and became the prototype for
these agents $here are currently %, chemical agents used in local anesthesia- lidocaine,
bupivacaine, and tetracaine are the most commonly used in clinical practice
Local anesthetics are used to decrease pain, temperature, touch proprioception, and
s"eletal muscle tone $he degree of these actions is dependent on dose and concentrations
of the drug, degree of hydrophobicity, and integrity of the application site Local
anesthetics are used in a variety of clinical situations, from topical application to the s"in
or mucosa membranes to in.ectable agents used for peripheral, central, or spinal nerve
bloc" /ome agents are used for specific indications in preparations intended for
anorectal or ophthalmic use
0echanism of Action: All local anesthetics reversibly bloc" nerve conduction by
decreasing nerve membrane permeability to sodium $his decreases the rate of membrane
depolari1ation, thereby increasing the threshold for electrical excitability All nerve fibers
are affected, albeit in a predictable se2uence: autonomic, sensory, motor $hese effects
diminish in reverse order /ince these drugs can also bloc" sodium channels in
myocardial tissues, an antiarrhythmic action is created Lidocaine and procainamide are
routinely used as antiarrhythmics 0exiletine and tocainide, oral congeners of lidocaine,
possess a mechanism of action similar to lidocaine and are also used as antiarrhythmics
!urrently, mexiletine and tocainide are not available in topical or in.ectable preparations
for local anesthetic purposes Finally, lidocaine has also been used as an alternative agent
in the treatment of status epilepticus 3hile the mechanism of this effect is unclear, it is
li"ely that bloc"ade of neuronal sodium channels may be involved
4istinguishing Features: /ince the mechanism of action is similar, local anesthetics are
selected based on their pharmacodynamic and pharmaco"inetic features (deally, the
agent should possess low systemic toxicity, have a rapid onset of action, have a duration
of action long enough to complete the intended procedure, and not be irritating to the
tissue
Local anesthetics are listed according to their basic chemical class $ypically, local
anesthetics are grouped as either 5amides5 or 5esters5 $he 5esters5 include the prototype
procaine, and also ben1ocaine, butamben picrate, chloroprocaine, cocaine, proparacaine,
and tetracaine $hese agents are derivatives of paraaminoben1oic acid and are hydroly1ed
by plasma esterases $he 5amides5 include the prototype lidocaine, and also bupivacaine,
dibucaine, etidocaine, mepivacaine, prilocaine, and ropivacaine $he amides are
derivatives of aniline and are metaboli1ed primarily in the liver, and the metabolites are
then excreted renally Lidocaine, mepivacaine, and tetracaine also may have some biliary
excretion 4yclonine and pramoxine do not fit into either chemical classification and
might be suitable alternatives in patients with allergies to amides or esters 6upivacaine is
commonly used for epidural anesthesia in obstetrics because of its motor#sparing
properties and long duration although its systemic toxicity is greater than less potent
agents such as lidocaine or mepivacaine
/election of a local anesthetic is based largely on its pharmaco"inetics $he site and route
of administration can influence the characteristics of an agent 0ost local anesthetics
have a rapid onset when administered parenterally for infiltrative anesthesia, the fastest
being lidocaine 7'+#% minute8 followed by prilocaine 7%#9 minutes8 $he average onset of
action for the remaining agents is between :#+ minutes $he exception is tetracaine,
which can ta"e up to %+ minutes $he onset of action is longer with epidural
administration, averaging approximately +#%+ minutes for most local anesthetics
Procaine 7%+#9+ minutes8, tetracaine 79'#:' minutes8, and bupivacaine 7%'#9' minutes8
all have slightly slower onsets of action when administered epidurally than the
other agents
$he duration of action of the in.ectable anesthetic agents is important in their selection
for various procedures Procaine and chloroprocaine are the shortest#acting agents 7'9+#
'+ hours8, followed by lidocaine, mepivacaine, and prilocaine, which have slightly
longer durations of action 7'+#%+ hours8 $he longer#acting agents include tetracaine 79#
: hours8, bupivacaine 79#) hours8, etidocaine 79#: hours8, and ropivacaine ;opivacaine
exhibits a duration of &#%: hours when used for peripheral nerve bloc" but the effective
analgesia when administered epidurally is only 9+#, hours Epinephrine prolongs the
duration of action of most local anesthetics, however, this is not always a consistent
finding /pinally administered local anesthetics tend to have a slightly shorter duration of
action compared with other routes of administration
Applied topically, local anesthetics reach pea" effect at different times when applied to
mucous membranes 6en1ocaine is the fastest 7% minute8, followed by lidocaine <
cocaine = pramoxine = tetracaine = dyclonine and = dibucaine All of the topical products
have a duration of action ranging from about :' minutes to an hour !ocaine>s effects can
last up to 9 hours after topical application, and dibucaine has the longest duration of
action at :#) hours
$he topical local anesthetics are used for s"in and mucous membrane anesthesia 0ost
agents are used for both indications, except dibucaine, butamben picrate, and pramoxine,
which are not used on mucous membranes Pramoxine was found to be too irritating to
the eyes and nose 4yclonine and cocaine are not used in s"in disorders, perhaps because
they are well absorbed through the s"in
$etracaine and proparacaine are available as ophthalmic preparations 6en1ocaine and
pramoxine are also included in a variety of anorectal preparations 6en1ocaine candy or
gum is used as a diet aid in combination with dieting (t wor"s by decreasing the ability to
detect degrees of sweetness by altering taste perception
Adverse ;eactions: /ystemic absorption of local anesthetics can produce increased serum
concentrations, resulting in toxicity in the !?/ or the cardiovascular system $he longer
the duration of action, the higher the potential for toxicity, which can include neurolysis
with sloughing and necrosis of surrounding tissue Parenteral local anesthetics are often
coadministered epinephrine or other local vasoconstrictor to delay systemic absorption,
prolong duration of action, and promote local hemostasis
Local hypersensitivity reactions are more li"ely to occur with the 5ester5 type of local
anesthetics $he 5amide5 type of local anesthetics has not demonstrated cross#sensitivity
with the esters /ome of the topical preparations contain tartra1ine and sulfites and should
be used with caution in patients with these hypersensitivities