Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

LOCAL ANESTHETICS
(e.g. for cesarean section or hindlimb orthopedic
procedures)
● intravenous regional administration to provide analgesia
for surgery of the distal limbs.
In addition, infusions of the local anesthetic lidocaine
have a sparing effect on the MAC of volatile anesthetics
and have been used as an adjunct to general anesthesia.
Infusions are also occasionally used to treat pain that is
resistant to conventional analgesic therapies. Furthermore,
lidocaine is an important antiarrhythmic and is a
drug of choice in the treatment of malignant ventricular
arrhythmias (see Chapter 17).
Mechanism of action
An electrically excitable cell, such as a nerve fiber, is
able to generate an action potential in response to membrane
depolarization. This activity is dependent on the
function of voltage-gated ion channels in the cell membrane.
At rest there is a potential difference across the
cell membrane of approximately 60–90 mV, the intracellular
environment being negative relative to the extracellular
environment. During excitation, membrane
depolarization opens voltage-activated sodium channels
allowing sodium ions to flow into the cell, down a concentration
gradient. This influx of positive charge produces
further depolarization (i.e. the interior becomes
less negative) and an action potential is generated. Two
events serve to restore the resting membrane potential.
Delayed opening of voltage-activated potassium channels
produces an outward current of positive ions. In
addition, the sodium channels are inactivated. These ion
currents also require concentration gradients, which are
restored by the sodium–potassium pump.
Local anesthetics inhibit both the initiation and conduction
of action potentials by preventing the inward
sodium current. They bind to receptors within the
sodium channel to block the flow of ions. Access to the
binding site cannot be gained through the external
opening of the ion channel. The local anesthetic must
first diffuse through the axon membrane and then enter
the ion channel via the opening on the internal surface
of the membrane. Alternatively the drug can reach
the ion channel by diffusing directly through the
membrane.
Local anesthetics can potentially block impulse conduction
in all types of nerve fiber but differences in
sensitivity exist. Small-diameter fibers are more sensitive
than large-diameter fibers and a myelinated neurone
will block more readily than an unmyelinated neurone
of similar size. Thus nociceptive afferents (Aδ and C
fibers) are more susceptible than motor neurones and in
theory it is possible to achieve analgesia without loss of
motor function. Autonomic nerve fibers are also very
sensitive to the effects of local anesthetic. Another factor
that influences susceptibility is the discharge rate of an
axon and rapidly firing axons are blocked most readily.
This form of use-dependence can be related to the functional
state of the ion channel. The channel is more
susceptible when in the open state since this improves
access to the binding site. Sensory fibers, including nociceptive
afferents, have a high firing rate and this serves
to enhance their susceptibility to local anesthetics.
Formulations and dose rates
A large number of different local anesthetic preparations are available
for topical anesthesia.
• EMLA cream (eutectic mixture of local anesthetic) contains a
mixture of lidocaine (2.5%) and prilocaine (2.5%). It can be
used to provide topical anesthesia of the skin prior to
venepuncture. After application the skin should be covered with
an occlusive dressing. Sixty min may be required for the
maximum effect to develop.
• A clear solution of 2% lidocaine administered by a metered
dose spray is available for topical anesthesia of the larynx. Each
spray contains 2–4 mg of lidocaine. Lidocaine is also available
as a 1% gel to facilitate procedures such as urethral
catheterization.
• A 0.5% solution of proxymetacaine is commonly used to
desensitize the cornea.
Local anesthetics are also available as aqueous solutions for injection
(e.g. 5% procaine, 2% lidocaine, 2% mepivacaine, 0.5% bupivacaine,
0.2% ropivacaine).
• Bupivacaine, mepivacaine and ropivacaine have an asymmetrical
carbon and exist as optical isomers. Racemic mixtures of
bupivacaine and mepivacaine are used most frequently in
veterinary medicine; however, the S isomer of bupivacaine is
available separately and is less toxic. Ropivacaine is only
available as the S enantiomer.
• Some formulations of lidocaine contain low concentrations of
adrenaline (epinephrine) and therefore produce a localized
vasoconstriction. This serves to reduce systemic absorption of
the local anesthetic, thereby prolonging its duration of effect
and reducing the risk of systemic toxicity. Such preparations
should not be used for intravenous regional analgesia. Neither
are they recommended for desensitization of an extremity such
as a digit.
Local anesthetic techniques
In small animal patients lidocaine and bupivacaine are
the most popular agents for local anesthetic techniques
(see Table 5.3). Mepivacaine is occasionally used.
Ropivacaine is a newer agent that is gaining popularity
in human anesthesia and reportedly causes less
motor blockade. Other texts should be consulted for a
description of the techniques themselves (see Further
reading).
To reduce the risk of systemic toxicity, total doses of
6 mg/kg lidocaine, 5 mg/kg mepivacaine or 2 mg/kg
bupivacaine should not be exceeded in dogs. Toxic
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