Local anesthetics

Local anesthetics

Local anesthetics are drugs that suppress pain by blocking impulse conduction along axons. Conduction is blocked only in neurons located near the site of administration. The great advantage of local anesthesia, compared with inhalation anesthesia, is that pain can be suppressed without causing generalized depression of the entire nervous system. Hence, local anesthetics carry much less risk than do general anesthetics.

We begin the chapter by considering the pharmacology of the local anesthetics as a group. After that, we discuss three prototypic agents: procaine, lidocaine, and cocaine. We conclude by discussing specific routes of anesthetic administration.

Basic pharmacology of the local anesthetics

Classification

There are two major groups of local anesthetics: esters and amides. As shown in Figure 26–1, the ester-type anesthetics, represented by procaine [Novocain], contain an ester linkage in their structure. In contrast, the amide-type agents, represented by lidocaine [Xylocaine], contain an amide linkage. The ester-type agents and amide-type agents differ in two important ways: (1) method of inactivation and (2) promotion of allergic responses. Contrasts between the esters and amides are summarized in Table 26–1.

TABLE 26–1

Contrasts Between Ester and Amide Local Anesthetics

Property	Ester-type Anesthetics	Amide-type Anesthetics
Characteristic Chemistry	Ester bond	Amide bond
Representative Agent	Procaine	Lidocaine
Incidence of Allergic Reactions	Low	Very low
Method of Metabolism	Plasma esterases	Hepatic enzymes

Mechanism of action

Local anesthetics stop axonal conduction by blocking sodium channels in the axonal membrane. Recall that propagation of an action potential requires movement of sodium ions from outside the axon to the inside. This influx takes place through specialized sodium channels. By blocking axonal sodium channels, local anesthetics prevent sodium entry, and thereby block conduction.

Selectivity of anesthetic effects

Local anesthetics are nonselective modifiers of neuronal function. That is, they will block action potentials in all neurons to which they have access. The only way we can achieve selectivity is by delivering the anesthetic to a limited area.

Although local anesthetics can block traffic in all neurons, blockade develops more rapidly in some neurons than in others. Specifically, small, nonmyelinated neurons are blocked more rapidly than large, myelinated neurons. Because of this differential sensitivity, some sensations are blocked sooner than others. Specifically, perception of pain is lost first, followed in order by perception of cold, warmth, touch, and deep pressure.

Be aware that the effects of local anesthetics are not limited to sensory neurons: These drugs also block conduction in motor neurons, which is why your face looks funny when you leave the dentist.

Time course of local anesthesia

Ideally, local anesthesia would begin promptly and would persist no longer (or shorter) than needed. Unfortunately, although onset of anesthesia is usually rapid (see Tables 26–2 and 26–3 below), duration of anesthesia is often less than ideal. In some cases, anesthesia persists longer than needed. In others, repeated administration is required to maintain anesthesia of sufficient duration.

Onset of local anesthesia is determined largely by the molecular properties of the anesthetic. Before anesthesia can occur, the anesthetic must diffuse from its site of administration to its sites of action within the axon membrane. Anesthesia is delayed until this movement has occurred. The ability of an anesthetic to penetrate the axon membrane is determined by three properties: molecular size, lipid solubility, and degree of ionization at tissue pH. Anesthetics of small size, high lipid solubility, and low ionization cross the axon membrane rapidly. In contrast, anesthetics of large size, low lipid solubility, and high ionization cross slowly. Obviously, anesthetics that penetrate the axon most rapidly have the fastest onset.

Termination of local anesthesia occurs as molecules of anesthetic diffuse out of neurons and are carried away in the blood. The same factors that determine onset of anesthesia (molecular size, lipid solubility, degree of ionization) also help determine duration. In addition, regional blood flow is an important determinant of how long anesthesia will last. In areas where blood flow is high, anesthetic is carried away quickly, and hence effects terminate with relative haste. In regions where blood flow is low, anesthesia is more prolonged.

Use with vasoconstrictors

Local anesthetics are frequently administered in combination with a vasoconstrictor, usually epinephrine. The vasoconstrictor decreases local blood flow and thereby delays systemic absorption of the anesthetic. Delaying absorption has two benefits: It prolongs anesthesia and reduces the risk of toxicity. Why is toxicity reduced? First, because absorption is slowed, we can use less anesthetic. Second, by slowing absorption, we can establish a more favorable balance between the rate of entry of anesthetic into circulation and the rate of its conversion into inactive metabolites.

It should be noted that absorption of the vasoconstrictor itself can result in systemic toxicity (eg, palpitations, tachycardia, nervousness, hypertension). If adrenergic stimulation from absorption of epinephrine is excessive, symptoms can be controlled with alpha- and beta-adrenergic antagonists.

Fate in the body

Absorption and distribution.

Although administered for local effects, local anesthetics do get absorbed into the blood and become distributed to all parts of the body. The rate of absorption is determined largely by blood flow to the site of administration.

Metabolism.

The process by which a local anesthetic is metabolized depends on the class—ester or amide—to which it belongs. Ester-type local anesthetics are metabolized in the blood by enzymes known as esterases. In contrast, amide-type anesthetics are metabolized by enzymes in the liver. For both types of anesthetic, metabolism results in inactivation.

The balance between rate of absorption and rate of metabolism is clinically significant. If a local anesthetic is absorbed more slowly than it is metabolized, its level in blood will remain low, and hence systemic reactions will be minimal. Conversely, if absorption outpaces metabolism, plasma drug levels will rise, and the risk of systemic toxicity will increase.

Adverse effects

Adverse effects can occur locally or distant from the site of administration. Local effects are less common.

Central nervous system.

When absorbed in sufficient amounts, local anesthetics cause central nervous system (CNS) excitation followed by depression. During the excitation phase, seizures may occur. If needed, excessive excitation can be managed with an IV benzodiazepine (diazepam or midazolam) or with IV thiopental (a rapid-acting barbiturate). Depressant effects range from drowsiness to unconsciousness to coma. Death can occur secondary to depression of respiration. If respiratory depression is prominent, mechanical ventilation with oxygen is indicated.

Cardiovascular system.

When absorbed in sufficient amounts, local anesthetics can affect the heart and blood vessels. In the heart, these drugs suppress excitability in the myocardium and conducting system, and thereby can cause bradycardia, heart block, reduced contractile force, and even cardiac arrest. In blood vessels, anesthetics relax vascular smooth muscle; the resultant vasodilation can cause hypotension. As discussed in Chapter 49 (Antidysrhythmic Drugs), the cardiosuppressant actions of one local anesthetic—lidocaine—are exploited to treat dysrhythmias.

Allergic reactions.

An array of hypersensitivity reactions, ranging from allergic dermatitis to anaphylaxis, can be triggered by local anesthetics. These reactions, which are relatively uncommon, are much more likely with the ester-type anesthetics (eg, procaine) than with the amides. Patients allergic to one ester-type anesthetic are likely to be allergic to all other ester-type agents. Fortunately, cross-hypersensitivity between the esters and amides has not been observed. Hence, the amides can be used when allergies contraindicate use of ester-type anesthetics. Because they are unlikely to cause hypersensitivity reactions, the amide-type anesthetics have largely replaced the ester-type agents when administration by injection is required.

Use in labor and delivery.

Local anesthetics can depress uterine contractility and maternal expulsion effort. Both actions can prolong labor. Also, local anesthetics can cross the placenta, causing bradycardia and CNS depression in the neonate.

Methemoglobinemia.

Topical benzocaine can cause methemoglobinemia, a blood disorder in which hemoglobin is modified such that it cannot release oxygen to tissues. If enough hemoglobin is converted to methemoglobin, death can result. Methemoglobinemia has been associated with benzocaine liquids, sprays, and gels. Most cases were in children under 2 years old treated with benzocaine gel for teething pain. Owing to the risk of methemoglobinemia, topical benzocaine should not be used in children under the age of 2 years without the advice of a healthcare professional, and should be used with caution in older children and adults when applied to mucous membranes of the mouth.

Properties of individual local anesthetics

Procaine

Procaine [Novocain], introduced in 1905, is the prototype of the ester-type local anesthetics. The drug is not effective topically, and hence must be given by injection. Administration in combination with epinephrine delays absorption. Although procaine is readily absorbed, systemic toxicity is rare. Why? Because plasma esterases rapidly convert the drug to inactive, nontoxic products. Being an ester-type anesthetic, procaine poses a greater risk of allergic reactions than do the amide-type anesthetics. Individuals allergic to procaine should be considered allergic to all other ester-type anesthetics, but not to the amides.

For many years, procaine was the local anesthetic most preferred for use by injection. However, with the development of newer agents, use of procaine has sharply declined. Once popular in dentistry, procaine is rarely employed in that setting today.

Procaine hydrochloride [Novocain] is available in solution for administration by injection. Epinephrine (at a final concentration of 1:100,000 or 1:200,000) may be combined with procaine to delay absorption.

Lidocaine

Lidocaine, introduced in 1948, is the prototype of the amide-type agents. One of today’s most widely used local anesthetics, lidocaine can be administered topically and by injection. Anesthesia with lidocaine is more rapid, more intense, and more prolonged than with an equal dose of procaine. Effects can be extended by coadministration of epinephrine. Allergic reactions are rare, and individuals allergic to ester-type anesthetics are not cross-allergic to lidocaine. If plasma levels of lidocaine climb too high, CNS and cardiovascular toxicity can result. Inactivation is by hepatic metabolism.

In addition to its use in local anesthesia, lidocaine is employed to treat dysrhythmias (see Chapter 49). Control of dysrhythmias results from suppression of cardiac excitability secondary to blockade of cardiac sodium channels.

Lidocaine hydrochloride [Xylocaine, others] is available in several formulations (cream, ointment, jelly, solution, aerosol, patch) for topical administration. Lidocaine for injection is available in concentrations ranging from 0.5% to 5%. Some injectable preparations contain epinephrine (1:50,000, 1:100,000, or 1:200,000).

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Tags: Pharmacology for Nursing Care

Jul 24, 2016 | Posted by admin in NURSING | Comments Off

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