LOCAL ANESTHETICS

LOCAL ANESTHETICS

Local anesthetics are generally applied locally and block nerve conduction of sensory impulses from the periphery to the CNS. Local anesthesia refers to loss of sensation in a limited region of the body. This is accomplished by disruption of afferent neural traffic via inhibition of impulse generation or propagation. Such blockade may bring with it other physiologic changes such as muscle paralysis and suppression of somatic or visceral reflexes, and these effects might be desirable or undesirable.

Depending on the particular circumstances, the most widely used of these compounds are bupivacaine, tetracaine, mepivacaine, procaine, ropivacaine, and lidocaine. Of these, lidocaine is the most frequently employed. At physiologic pH, these compounds are charged, it is this ionized form that interacts with the protein receptor of the Na⁺ channel to inhibit its function and, thereby, achieve local anesthesia. Although local anesthetics are often used as analgesics, it is their ability to provide complete loss of all sensory modalities that is their distinguishing characteristic.

Chemistry: Most of the local anesthetic agents consist of a lipophilic group (eg, an aromatic ring) connected by an intermediate chain via an ester or amide to an ionizable group (eg, a tertiary amine).

Mechanism of action: The primary mechanism of action of local anesthetics is blockade of voltage-gated sodium channels. The excitable membrane of nerve axons, like the membrane of cardiac muscle and neuronal cell bodies, maintains a resting transmembrane potential of –90 to –60 mV. During excitation, the sodium channels open, and a fast, inward sodium current quickly depolarizes the membrane toward the sodium equilibrium potential (+40 mV). As a result of this depolarization process, the sodium channels close (inactivate) and potassium channels open. The outward flow of potassium repolarizes the membrane toward the potassium equilibrium potential (about –95 mV); repolarization returns the sodium channels to the rested state with a characteristic recovery time that determines the refractory period. The transmembrane ionic gradients are maintained by the sodium pump. These ionic fluxes are similar to, but simpler than, those in heart muscle, and local anesthetics have similar effects in both tissues.

Commonly used local anesthetic agents:

Articaine: Articaine is the most widely used local anaesthetic agent in dentistry in a number of European countries. The amide structure of articaine is similar to that of other local anaesthetics, but it contains an additional ester group which is quickly hydrolysed by esterases. High performance liquid chromatography has been used to determine the concentrations of articaine and its metabolite articainic acid in serum.

Benzocaine: It pronounced lipophilicity has relegated its application to topical anesthesia.  Elevated levels can be due to inborn errors, or can occur with exposure to an oxidizing agent, and such is the case with significant exposure to benzocaine.

Bupivacaine: Based on concerns for cardiotoxicity, bupivacaine is often avoided

for techniques that demand high volumes of concentrated anesthetic, such as epidural or peripheral nerve blocks performed for surgical anesthesia. In contrast, relatively low concentrations (≤ 0.25%) are frequently used to achieve prolonged peripheral anesthesia and analgesia for postoperative pain control, and the drug enjoys similar popularity where anesthetic infiltration is used to control pain from a surgical incision. It is often the agent of choice for epidural infusions used for postoperative pain control and for labor analgesia.

Chloroprocaine: Chloroprocaine gained widespread use as an epidural agent in obstetric anesthesia, where its rapid hydrolysis served to minimize risk of systemic toxicity or fetal exposure. Although chloroprocaine was never exonerated with respect to the early neurologic injuries associated with epidural anesthesia, it is now well appreciated that high doses of any local anesthetic, which are not required to achieve spinal anesthesia, are capable of inducing neurotoxic injury. In addition to chloroprocaine’s emerging use as a spinal anesthetic, the drug finds some current use as an epidural anesthetic, particularly in circumstances where there is an indwelling catheter and the need for quick attainment of surgical anesthesia, such as cesarean section in a laboring parturient with a compromised fetus.

Cocaine: Current clinical use of cocaine is largely restricted to topical anesthesia for ear, nose, and throat procedures, where its intense vasoconstriction can serve to reduce bleeding. Even here, use has diminished in favor of other anesthetics combined with vasoconstrictors because of concerns about systemic toxicity, as well as the inconvenience of dispensing and handling this controlled substance.

Etidocaine: It has a tendency to produce an inverse differential block  which is rarely a favorable attribute.

Levobupivacaine: It is less potent, and tends to have a longer duration of action, though the magnitude of these effects is too small to have any substantial clinical significance.

Lidocaine: Aside from the issue of a high incidence of TNS with spinal administration, lidocaine has had an excellent record as an intermediate duration anesthetic, and remains the  reference standard against which most anesthetics are compared.

Mepivacaine: It has a tendency toward vasoconstriction rather than vasodilation. This characteristic likely accounts for its slightly longer duration of action, which has made it a popular choice for major peripheral blocks.

Prilocaine: Prilocaine has the highest clearance of the amino-amide anesthetics, imparting reduced risk of systemic toxicity. Unfortunately, this is somewhat offset by its propensity to induce methemoglobinemia, which results from accumulation of one its metabolites, ortho-toluidine, an oxidizing agent. As a spinal anesthetic, prilocaine’s duration of action is slightly longer than that of lidocaine, and the limited data suggest it carries a low risk of TNS. It is gaining increasing use for spinal anesthesia in Europe, where it has been marketed specifically for this purpose.

Ropivacaine: Ropivacaine is an S (–) enantiomer in a homologous series that includes bupivacaine and mepivacaine, distinguished by its chirality, and the propyl group off the piperidine ring. It’s perceived reduced cardiotoxicity has led to widespread use for highvolume peripheral blocks. It is also a popular choice for epidural infusions for control of labor and postoperative pain.

Anesthetics, lipophilic, nerves, excitation