Tolerance of Local Anesthetics

Intradermal tolerance of local anesthetics can be used as a screening selection criterion for finding an optimal local anesthetic. Luduena Hoppe (1952), Luduena et al. (1960) determined intradermal irritancy by the trypan blue method according to Hoppe et al. (1950). 

Bulbring E, Wajda I (1945) Biological comparison of local anesthetics. J Pharmacol Exp Ther 85 78-84 Hergott J (1965) Evaluation of local tolerability of various production batches of local anesthetics. Personal communication. 

The adverse effects of local anesthetics are well established (3,4). The safety advantages claimed for newer agents have to be treated with much reserve. With increasing experience, discovery of optimal doses, and understanding of potency differences, the tolerability of... 

Relative the dose of bupivacaine varies with the anesthetic procedure, the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, the depth of anesthesia and degree of muscle relaxation required, the duration of anesthesia desired, individual tolerance, and the physical condition of the patient. Dosages of bupivacaine should be reduced for young, elderly and/or debilitated patients and patients with cardiac and/or liver disease. The rapid injection of a large volume of local anesthetic solution should be avoided. 

The low structural requirements for local anesthetic activity do not maintain in all classes of drugs. Structural requirements for biologic activity in fact follow a full continuum from those cases in which addition of a single carbon atom serves to abolish activity to the case of the local anesthetics that tolerate quite drastic alterations. 

Lidocaine hydrochloride Xylocaine) is the most commonly used local anesthetic. It is well tolerated, and in addition to its use in infiltration and regional nerve blocks, it is commonly used for spinal and topical anesthesia and as an antiarrhythmic agent (see Chapter 16). Lidocaine has a more rapidly occurring, more intense, and more prolonged duration of action than does procaine. 

Lidocaine s most common adverse effects—like those of other local anesthetics—are neurologic paresthesias, tremor, nausea of central origin, lightheadedness, hearing disturbances, slurred speech, and convulsions. These occur most commonly in elderly or otherwise vulnerable patients or when a bolus of the drug is given too rapidly. The effects are dose-related and usually short-lived seizures respond to intravenous diazepam. In general, if plasma levels above 9 mcg/mL are avoided, lidocaine is well tolerated. 

When tolerability of the compound is sufficient to allow systemic administration, local anesthetic drugs can be employed for relief of neuropathic pain and acute treatment of migraine headache in addition to the broad application for local anesthesia as proven for lidocaine... 

Lidocaine (synonyme lignocaine) was introduced as the first amide in 1944 and is the most commonly used LA today. It has a rapid onset of action with intermediate duration and an intermediate toxicity. The maximum tolerated dose with infiltration or injection is 200 mg (500 mg when combined with adrenaline). Lidocaine is dealkylated in the liver to monoethylglycine xylidide and glycine xylidide which retain local anesthetic activity. It is available in a variety of preparations including creams, gels, patches and solutions, often in combination with adrenaline. 

Transient neurological symptoms have been observed in patients after spinal anesthesia (Hampl et al. 1995). Activity and tolerability of new local anesthetics after intrathecal injection were studied in various animal species in order to predict both parameters for spinal (subarachnoid) anesthesia in patients. 

Pramoxine hydrochloride (anusol, tronothane, others) is a surface anesthetic agent that is not a benzoate ester. Its distinct chemical structure may help minimize the danger of crosssensitivity reactions in patients allergic to other local anesthetics. Pramoxine produces satisfactory surface anesthesia and is reasonably well tolerated on the skin and mucous membranes. It is too irritating to be used on the eye or in the nose. 

Local tolerability testing is an absolute requirement for any vaccine. One may reasonably expect that pure plasmids will be well tolerated, but technologies to improve the uptake of plasmids into cells or to render DNA vaccines more immunogenic may affect local tolerance. For example, coadministrations of hypo-osmotic solutions, local anesthetics, or cardiotoxin have been used in research, but induce cell necrosis at the injection site. 

Following the first description of allergy to a local anesthetic over 90 years ago, there was initially a steady stream of reports of reactions to the drugs consisting mainly of erythema or edema. With the introduction of the amide local anesthetics, the number of hypersensitivity reactions tapered off significantly, indicating that ester compounds were less well tolerated. Even today, however, reports of adverse reactions to local anesthetics occasionally appear, but the nature of the reactions cannot always be described... 

Topical ALA was also appHed to the treatment of superficial skin cancers with excellent results. It is less effective for nodular lesions. In this treatment, the ALA (10 to 40%) was appHed topically in leucerin cream for various periods (usuaUy 4 or 24 h) and then activated at 635 nm derived from a dye laser deHvering Hght doses up to 200 J/cm. In this treatment, the pain is suf cient to require local injection of an anesthetic prior to treatment. Most patients tolerate this weU. 

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