Download Local Anesthetics

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Local Anesthetics
"An anesthetic (or anaesthetic) is a drug that
causes anesthesia—reversible loss of
sensation. Local anesthetics produce
anesthesia by inhibiting excitation of nerve
endings or by blocking conduction in
peripheral nerves. This is achieved by
anesthetics reversibly binding to and inactivating sodium channels. Sodium influx
through these channels is necessary for the depolarization of nerve cell membranes and
subsequent propagation of impulses along the course of the nerve. When a nerve loses
depolarization and capacity to propagate an impulse, the individual loses sensation in the
area supplied by the nerve.
They contrast with analgesics (painkillers), which relieve pain without eliminating
sensation. These drugs are generally administered to facilitate surgery. A wide variety of
drugs are used in modern anesthetic practice. Many are rarely used outside of anesthesia,
although others are used commonly by all disciplines.
Anesthetics are categorized into two classes: general anesthetics, which cause a reversible
loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for
a limited region of the body while maintaining consciousness. Combinations of
anesthetics are sometimes used for their synergistic and additive therapeutic effects.
Adverse effects, however, may also be increased.
Cocaine was the first anesthetic to be discovered and is the only naturally occurring local
anesthetic; all others are synthetically derived. Cocaine was introduced into Europe in the
1800s following its isolation from coca beans. Sigmund Freud, the noted Austrian
psychoanalyst, used cocaine on his patients and became addicted through selfexperimentation.
Procaine, the first synthetic derivative of cocaine, was developed in 1904. Lofgren later
developed lidocaine, the most widely used cocaine derivative, during World War II in
1943.
Each of the local anesthetics have the suffix "-caine" in their names.
Procaine
Amethocaine
Cocaine
Lidocaine (also known as Lignocaine)
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Prilocaine
Bupivacaine
Levobupivacaine
Ropivacaine
Mepivacaine
Dibucaine
Local anesthetics are agents that prevent transmission of nerve impulses without causing
unconsciousness. They act by binding to fast sodium channels from within (in an open
state). Local anesthetics can be either ester or amide based.
Ester local anesthetics (e.g., procaine, amethocaine, cocaine) are generally unstable in
solution and fast-acting, and allergic reactions are common.
Amide local anesthetics (e.g., lidocaine, prilocaine, bupivacaine, levobupivacaine,
ropivacaine, mepivacaine and dibucaine) are generally heat-stable, with a long shelf life
(around 2 years). They have a slower onset and longer half-life than ester anesthetics,
and are usually racemic mixtures, with the exception of levobupivacaine (which is S(-) bupivacaine) and ropivacaine (S(-)-ropivacaine). These agents are generally used within
regional and epidural or spinal techniques, due to their longer duration of action, which
provides adequate analgesia for surgery, labor, and symptomatic relief.
**Note: Only preservative-free local anesthetic agents may be injected
intrathecally.
Example:
Thus, notice the difference in the labels on the bottles of Bupivacaine
used in the operating room. Anesthesia uses preservative-free. The
bupivacaine used on the surgical field has preservatives in it!
OTHER KEY POINTS FOR LOCAL
ANESTHESTICS:
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1. Local anesthetics block voltage-gated sodium channels by interrupting the
initiation and propagation of impulses in axons, but they have a wide variety of
other biologic actions, both desirable and undesirable.
2. The currently available local anesthetics are of two chemical classes: aminoesters
and aminoamides.
3. The low potency and lack of specificity of the available local anesthetics are due
in part to the structural constraint that they must have high solubility and diffuse
rapidly in both aqueous environments and the lipid phases of biologic membranes.
4. Aminoesters are primarily metabolized by plasma esterases; aminoamides are
metabolized primarily by hepatic cytochrome P450-linked enzymes in the liver.
5. The principal systemic toxicities of local anesthetics involve the heart (including
atrioventricular conduction block, arrhythmias, myocardial depression, and
cardiac arrest) and the brain (including irritability, lethargy, seizures, and
generalized CNS depression). Hypoxemia and acidosis exacerbate these toxicities.
Resuscitation after bupivacaine overdose is particularly difficult. Therefore,
prevention of intravascular injection or overdose is crucial, and major nerve
blockade should involve incremental, fractionated dosing.
6. Local anesthetics are directly toxic to nerve at the concentrations supplied in
commercial solutions. Intraneural concentrations during regional anesthesia are
generally (but not always) below the threshold for toxicity because of spread of
solutions through tissues and diffusion gradients from injection sites into nerve.
Injection into a constrained tissue space increases the risk of local toxicity.
7. Optimal use of local anesthetics in regional anesthesia requires an understanding
of the individual patient's clinical situation; the location, intensity, and duration of
regional anesthesia and analgesia required; anatomic factors affecting the
deposition of drug near nerves; proper drug selection and dosing; and ongoing
assessment of clinical effects after administration of local anesthetics.
8. Recent efforts have led to the development of several new formulations for topical
anesthesia. Single-stereoisomer (as opposed to a racemic mixture) formulations
have been developed in an effort to reduce systemic toxicity and improve sensory
selectivity.
9. Local anesthetics are increasingly being used for postoperative infusion and local
and systemic administration in the management of chronic pain. Further research
and development may lead to safe, more selective agents that can facilitate more
prolonged administration in the setting of acute or chronic pain.
Administration of Local Anesthetics
Again, for proper administration of local anesthetics, consider the individual
characteristics of the patient, dose of local anesthetic to be administered, presence or
absence of epinephrine, speed of administration, local tissue vascularity, and technique of
administration.
In each case, physicians should strive to find the smallest dose possible administered over
the longest period of time that achieves adequate anesthesia.
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Table. Dosages of Local Anesthetics
Drug
Onset
Maximum Dose
Duration
(with Epinephrine)
(with Epinephrine)
Lidocaine
Mepivacaine
Bupivacaine
Rapid
Rapid
Slow
4.5 mg/kg (7 mg/kg)
5 mg/kg (7 mg/kg)
2.5 mg/kg (3 mg/kg)
Ropivacaine
Medium 2-3 mg/kg
120 min (240 min)
180 min (360 min)
4 hours (8 h)
3 hours (6 h)
Levobupivacaine Medium 2.0 mg/kg or 400mg in 24 hrs 4-6 hours (8-12 h)
Procaine
Chloroprocaine
Etidocaine
Prilocaine
Tetracaine
Slow
8 mg/kg (10 mg/kg)
Rapid 10 mg/kg (15 mg/kg)
Rapid 2.5 mg/kg (4 mg/kg)
Medium 5 mg/kg (7.5 mg/kg)
Slow
1.5 mg/kg (2.5 mg/kg)
45 min (90 min)
30 min (90 min)
4 hours (8 h)
90 min (360 min)
3 hours (10 h)
Note: Epinephrine induces vasoconstriction, delaying absorption of the local anesthetic
for longer duration of action at the site of injection. By delaying absorption, epinephrine
also increases the safe dose of local anesthetic that may be administered.
Adverse reactions may occur following administration of local anesthetics and usually
result from administration of too much drug. Adverse reactions may also occur following
injection of very vascular sites or from accidental direct intravascular injection of the
drug. Deaths following local anesthetic administration are always a result of overdosage.
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Tissue toxicity can be achieved by all local anesthetics if “high” concentrations are used.
Adverse reactions occur primarily in the CNS (neurotoxicity) and cardiovascular system
(myotoxicity) because these tissues are also composed of excitable membranes, the target
of local anesthetic action.
Duration of Effects
Local anesthetics last for up to six hours, depending on the agent. The effects will be
prolonged if the preparation included epinephrine. Local anesthetics are poorly absorbed
through intact skin. One preparation that is absorbed through skin is a mixture of
prilocaine and lidocaine, however absorption is relatively slow and anesthesia is limited
to about five millimeters under the skin. This is enough to anesthetize the cutaneous
receptors. The preparation requires a minimum of 30 minutes to penetrate the skin and
will require longer to achieve maximum penetration.
Topically applied local anesthetics
may last for less than one hour."
Combined Information Sources:
Canadian Council on Animal Care (CCAC). (2011). CCAC Training module on
analgesia: Local anesthesia. Retrieved November 7, 2011, from
http://www.ccac.ca/en_/education/niaut/vivaria/analgesia
McLeod, I. K. (2008, July 22). Local anesthetics introduction and history. Retrieved
November 7, 2011, from http://emedicine.medscape.com/article/873879overview#showall
Miller's Anesthesia (6th edition). (2005). Chapter 14: Local anesthetics. Retrieved
November 7, 2011, from
http://www.anesthesia.net.tw/dokuwiki/doku.php?id=textbook:english:anesthesia