Local anesthetics: review of pharmacological considerations

Abstract

Local anesthetics have an impressive history of efficacy and safety in medical and dental practice. Their use is so routine, and adverse effects are so infrequent, that providers may understandably overlook many of their pharmacotherapeutic principles. The purpose of this continuing education article is to provide a review and update of essential pharmacology for the various local anesthetic formulations in current use. Technical considerations will be addressed in a subsequent article.

Figures

Figure 1.

Local anesthetic structure.

Figure 2.

Local anesthetic action. An injected local anesthetic exists in equilibrium as a quaternary salt (BH+) and tertiary base (B). The proportion of each is determined by the pKa of the anesthetic and the pH of the tissue. The lipid-soluble base (B) is essential for penetration of both the epineurium and neuronal membrane. Once the molecule reaches the axoplasm of the neuron, the amine gains a hydrogen ion, and this ionized, quaternary form (BH+) is responsible for the actual blockade of the sodium channel. The equilibrium between (BH+) and (B) is determined by the pH of the tissues and the pKa of the anesthetic (pH/pKa).

Figure 3.

Approximate serum concentrations and systemic influences of lidocaine.

Figure 4.

Local anesthetic serum concentrations. (See text for explanation. Adapted from Scott et al and Hersh et al.5)

Figure 5.

Molecular structures and allergenicity. Immunogenicity is attributable to medications having a phenyl ring with a para-amine substitution. This is found in sulfonamide antibiotics and compounds containing para-aminobenzoic acid (PABA) such as certain sunscreens and cosmetics. It is also found in methylparaben preservatives and ester local anesthetics such as procaine. Ester linkages (procaine) or side chains (articaine) are not immunogenic, nor is the sulfur atom of a thiophene ring (articaine). * indicates immunogenic moiety.

Figure 6.

Managing patients allergic to local anesthetics. Rule out common reactions misinterpreted as allergy, eg, syncope and tachycardia. Then establish that the nature of their reaction at least resembled a hypersensitivity reaction, eg, rash, pruritus, urticaria, or dyspnea. If the drug is known, choose another amide, free of vasopressor so no sulfites are present. Otherwise refer the patient to an allergist, for testing of sulfites and exemplary local anesthetics such as lidocaine, mepivacaine, and prilocaine. (Adapted from deShazo and Kemp.13)

Figure 7.

Cardiovascular effects of epinephrine. The following graph illustrates the typical cardiovascular response to epinephrine administered as a continuous intravenous infusion of 10 µg/min. (This is the amount contained in 1 mL of a 1 ∶ 100,000 concentration.) Epinephrine increases heart rate (HR) by activating beta-1 receptors in the sinoatrial node, the heart's normal pacemaker. It also activates beta-1 receptors on myocardial cells, increasing their contractility and increasing systolic blood pressure (SBP). However, it activates beta-2 receptors on systemic arteries producing vasodilation. This decline in arterial resistance produces a reduction in diastolic pressure (DBP). These effects result in little change of mean arterial pressure (MAP).