Types of Local Anesthetics

The caine suffix (lidocaine, procaine, and so on) usually identifies local anesthetics.. The first clinically useful local anesthetic identified was cocaine in 

FIGURE 12-1 Structure of lidocaine. The basic structure of a lipophilic and hydrophilic group connected by an intermediate chain is common to most local anesthetics. 

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B. Allergic reactions occur only to the ester type of local anesthetics. This is because the metabolism of all ester-linked local anesthetics leads to the formation of PABA, which is known to be allergenic to some individuals. Both cocaine and procaine are esters. However, cocaine is not employed in dental procedures. Therefore, the best choice is procaine. 

Mechanism of Action A surface or local anesthetic which is not chemically related to the "caine" types of local anesthetics. Decreases the neuronal membrane permeability to sodium ions, blocking both initiation and conduction of nerve impulses, therefore inhibiting depolarization of the neuron. Therapeutic Effect Temporarily relieves pain and itching associated with anogenital pruritus or irritation. 

Systemic effects are more likely to occur with long-acting anesthetics if an excessive dose is used, if absorption into the blood stream is accelerated for some reason, or if the drug is accidentally injected into the systemic circulation rather than into extravascular tissues.17 40 Other factors that can predispose a patient to systemic effects include the type of local anesthetic administered, as well as the route and method of administration.3 Therapists and other health care professionals should always be alert for signs of the systemic effects of local anesthetics in patients. Early symptoms of CNS toxicity include ringing/buzzing... 

Other types of local anesthetic can stimulate the CNS system but often lead to drowsiness. Individual compounds may cause other unwanted side effects, however. For example, at bhxxl concentrations of S /zg cm. lignocaine may produce muscle twitching, dysphoria, and euphoria. Both lignocaine and procaine can pnxluce symptoms of sedation, followed by unconsciousness. Cocaine, in common with some other local anesthetic agents, has an effect on nuuxl and behavior. 

Some antihistaminics, such as promethazine and diphenhydramine, have local anesthetic properties. They may be used substitutively in patients who are allergic to both amide and ester types of local anesthetics. Some phenothiazine antihistaminics, such as promethazine, have alpha-adrenergic blocking effects. Therefore, like phenothiazine neuroleptics, promethazine may cause orthostatic hypotension. 

The challenge at hand is to achieve optimal patient comfort while avoiding the risks of oversedation and respiratory depression. The type of local anesthetic and the dose delivered are important in addition to appropriate conscious sedation. As a general rule, it is desirable to select an anesthetic agent that is rapid in onset in combination with one that offers sustained action. A list of pharmacologic properties of commonly used local anesthetic agents is found in Table 4.6. 

The vasoconstrictor actions of epinephrine and norepinephrine have been used to prolong the action of local anesthetics by reducing local blood flow in the region of the injection. Epinephrine has been used as a topical hemostatic agent for the control of local hemorrhage. Norepinephrine is infused intravenously to combat systemic hypotension during spinal anesthesia or other hypotensive conditions in which peripheral resistance is low, but it is not used to combat the hypotension due to most types of shock. In shock, marked sympathetic activity is already present, and perfusion of organs, such as the kidneys, may be jeopardized by norepinephrine administration. 

Another important reason for preferential blockade of sensory fibers follows directly from the state- and use-dependent mechanism of action of local anesthetics. Blockade by these drugs is more marked at higher frequencies of depolarization. Sensory (pain) fibers have a high firing rate and a relatively long action potential duration. Motor fibers fire at a slower rate and have a shorter action potential duration. Type A delta and C fibers are smaller-diameter fibers that participate in high-frequency pain transmission. Therefore, these fibers are blocked earlier and with lower concentrations of local anesthetics than are the large A alpha fibers. 

Peripheral nerve block. The anesthetic is injected close to the nerve trunk so that transmission along the peripheral nerve is interrupted.61 This type of local anesthesia is common in dental procedures (restorations, tooth extractions, and so on) and can also be used to block other peripheral nerves to allow certain surgical procedures of the hand, foot, shoulder, and so forth. ii.56.65 xnjection near larger nerves (femoral, sciatic) or around a nerve plexus (brachial plexus)... 

Finally, therapists may work with patients who are receiving central neural blockade in the form of an epidural or spinal injection. These procedures are common during natural and caesarean childbirth and in some other surgical procedures. Administration of local anesthetics into the spaces around the spinal cord are also used to treat individuals with severe and chronic pain—that is, patients recovering from extensive surgery, patients who have cancer, or patients with other types of intractable pain. In these situations, therapists may notice that an indwelling catheter has been placed in the patient s epidural or subarachnoid space to allow repeated or sustained administration of the spinal anesthesia. 

This question of direct interaction with nerve proteins or indirect interaction via membrane perturbation has also been tackled by ESR spectroscopy. Two types of labeling have been used fatty acids for lipid labeling and maleimide for frog nerve proteins. The anesthetics used were halothane as an example of a general anesthetic and procaine, lidocaine, and tetracaine as examples of local anesthetics. The latter interact primarily with head groups but can also merge into the hydrophobic hydrocarbon... 

The development of local anesthetics and their structure-activity relationship are described in Chapter 13 in the drug screening section. Suffice it to say that the development of these drugs has opened up an entirely new era in relieving pain in the conscious patient. When applied locally to nerve tissue in appropriate concentrations, local anesthetics reversibly block the action potentials responsible for nerve conduction. They act on any part of the nervous system and on every type of nerve fiber. Their action is reversible at clinically relevant concentrations and nerve function recovers... 

Tricyclic antidepressants act on both presynaptic and postsynaptic neurons, as well as on alpha- and beta-adrenoceptors. Because their principal action is to block the re-uptake of noradrenaline at the presynaptic neuron, they potentiate the hypertensive effects of both directly acting and indirectly acting amines (158,159). The hypertensive effects of phenylephrine are increased by a factor of 2-3, and of noradrenaline by a factor of 4-8. Even the administration of local anesthetics containing noradrenaline as a vasoconstrictor has proven fatal. The types of... 

The liver, for the amide-type anesthetics, or plasma esterases, for the ester-type, can eliminate large amoimts of local anesthetics. Within 30 to 60 minutes sufficient elimination of the overdose usually occurs to make the CNS stimulation or depression short-lived. Management objectives should therefore center on temporary respiratory and cardiovascular support. Administration of supplemental oxygen usually rapidly restores normal CNS function. In patients in whom cardiovascular collapse is evident, vasopressor therapy may take the form of metaraminol bitartrate 1% (Aramine) given intramuscularly or intravenously. The effect of this potent short-acting vasopressor lasts 20 to 60 minutes, depending on route of administration. 

Various types of immunodepressant effects of local anesthetics can be detected by laboratory testing, although they may have no clinical significance. Lidocaine dose-dependently inhibits EA rosetting by human lymphocytes. In vitro depression of human leukocyte random motility and phagocytosis has also been reported (SED-11, 220) (41). 

Lidocaine produces faster, more intense, longer-lasting, and more extensive anesthesia than does an equal concentration of procaine. Unlike procaine, it is an aminoethyla-mide and is the prototypical member of this class of local anesthetics. It is a good choice for individuals sensitive to ester-type local anesthetics. Although it is effective when used without any vasoconstrictor, in the presence of epinephrine, the rate of absorption and the toxicity are decreased, and the duration of action usually is prolonged (see also Figure 80). 

The types of nerve fibers that are blocked when a local anesthetic is injected about a mixed peripheral nerve depend on the concentration of drug used, nerve-fiber size, intemodal distance, and frequency and pattern of nerve-impulse transmission ("see above). Anatomical factors are similarly important. Nerves in the outer mantle of the mixed nerve are blocked first. These fibers usually are distributed to more proximal anatomical structures than are those situated near the core of the mixed nerve and often are motor. If the volume and concentration of local anesthetic solution deposited about the nerve are adequate, the local anesthetic eventually will diffuse inward in amounts adequate to block even the most centrally located fibers. Since removal of local anesthetics occurs primarily in the core of a mixed nerve or nerve trunk, where the vascular supply is located, the duration of blockade of centrally located nerves is shorter than that of more peripherally situated fibers. 

The choice of local anesthetic and the amount and concentration administered are determined by the nerves and the types of fibers to be blocked, the required duration of anesthesia, and the size and health of the patient. For blocks of 2-4 hours, lidocaine (1-1.5%) can be used in the amounts recommended above (see Infiltration Anesthesia ). Mepivacaine (up to 7 mg/kg of a 1-2% solution) provides anesthesia that lasts about as long as that from lidocaine. Bupivacaine (2-3 mg/kg of a 0.25-0.375% solution) can be used when a longer duration of action is required. Addition of 5 pg/mL epinephrine slows systemic absorption and, therefore, prolongs duration and lowers the plasma concentration of the intermediate-acting local anesthetics. 

The concentration of local anesthetic used determines the type of nerve fibers blocked The highest concentrations are used when sympathetic, somatic sensory, and somatic motor blockade are required. Intermediate concentrations allow somatic sensory anesthesia without muscle relaxation. Low concentrations will block only preganglionic sympathetic fibers. A significant difference between epidural and spinal anesthesia is that the dose of local anesthetic used can produce high concentrations in blood following absorption from the epidural space. 

The ester group of ester-type local anesthetics is hydrolyzed by plasma (and tissue) pseudocholinesterases. These drugs are poor substrates for acetylcholinesterase the activity of this enzyme does not play a part in terminating the actions of local anesthetics. Individuals with genetically based defects in pseudocholinesterase activity are unusually sensitive to procaine and other esters. The answer is (B). 

An understanding of the metabolism of local anesthetics is important in clinical practice, because the overall toxicity of a drug depends not only on its uptake and tissue distribution but also on how it is deactivated in vivo. The amino ester-type local anesthetics are rapidly hydrolyzed by plasma cholinesterase (also known as pseudocholinesterase), which is widely distributed in body tissues. These compounds can therefore be metabolized in the blood, kidneys, and liver and, to a lesser extent, at the site of administration. For example, both procaine and benzocaine are easily hydrolyzed by cholinesterase into PABA and the corresponding N,N -diethylaminoethyl alcohol. 

Study of Local Anesthetics on Toxicity and Protein Binding. Discussion Upon Conditions of Analysis with Amide-Type Local Anesthetic Solution Extracted from Serum by Gas Chromatography Nippon Shika Masui Gakkai Zasshi 7(l) 34-43 (1979) CA 91 49180b... 

Use of a large, lipophilic nitrogenous component results 3 1 idocaine like, local anesthetic type cardiac anti-... 

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