Abstract

Local anesthetic structure. All local anesthetics consist of 3 principal components, each contributing a distinct property.

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 species (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. Presumably, it binds within the sodium channel near the inner surface of the neuronal membrane.

Systemic influences of lidocaine.

Serum concentrations following 3 routes of administration.

Carrier + hapten = immunogen.

Sulfonamide as hapten.

Ester linkages of procaine and articaine.

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, dyspnea). If the drug is known, choose another amide, free of vasopressor so no bisulfites are present. Otherwise, refer to an allergist, sharing this figure if necessary. Adapted from deShazo RD, Kemp SF. JAMA. 1997;278:1903.

Cardiovascular influences of epinephrine. Patients received submucosal infiltration of 3 cartridges (5.4 mL) of 2% lidocaine and 2% lidocaine with epinephrine 1 : 100,000. Changes in cardiovascular parameters were recorded as percent change. Heart rate (HR), stroke volume (SV), and cardiac output (CO) determine systolic blood pressure. Peripheral resistance (PR) determines diastolic blood pressure. Mean arterial pressure (MAP) is calculated as (SBP + 2 × DBP)/3. Adapted from Dionne et al.17

Cardiovascular influences of norepinephrine (and levonordefrin) versus epinephrine.18 A. Both drugs stimulate Beta₁ receptors on cardiac muscle, which increase myocardial contractility. This results in an increase in systolic pressure. B. Both drugs stimulate alpha receptors on vessels, which causes them to constrict. Submucosal vessels contain only alpha receptors, so both drugs produce local vasoconstriction when injected submucosally. But submucosal vessels are not illustrated here; they do not influence diastolic pressure. Systemic arteries influence diastolic pressure and contain Beta₂ receptors, which vasodilate and are far more numerous than alpha receptors. Norepinephrine has no affinity for Beta₂ receptors and constricts systemic arteries by activating the alpha receptors, even though they are less numerous. This increases diastolic pressure. Epinephrine, which has Beta₂ as well as alpha receptor activity, produces vasodilation and a reduction in diastolic pressure. C. Both drugs stimulate Beta₁ receptors on the Sino-atrial node, which increases heart rate. But this potential effect from norepinephrine is overridden by a reflex explained as follows. Notice that epinephrine has no influence on mean arterial pressure; systolic pressure increases but diastolic decreases and negates any effect on mean arterial pressure. Norepinephrine increases systolic, diastolic, and mean arterial pressures. The increase in mean arterial pressure stimulates baroreceptors in the carotid sinus, which trigger a vagal slowing of heart rate.

Mechanism of epinephrine–beta-blocker interaction. The cardiovascular influences of epinephrine are mediated via alpha, Beta-1, and Beta-2 receptors and are altered in patients medicated with nonselective beta blockers. These graphs distinguish typical cardiovascular responses after a 10-to 20-μg test dose of epinephrine in a normal versus a beta-blocked patient (see Table 4 for additional explanation). Note that the key underlying mechanism involves the influence of epinephrine on systemic vascular resistance and subsequent diastolic blood pressure (DBP).