Local anesthetics application

Brouneus, F., et al. 2001. Diffusive transport properties of some local anesthetics applicable for iontophoretic formulation of the drugs. Int J Pharm 218 57. 

The various methods of administering a local anesthetic include topical application, local infiltration, or regional anesfliesia... 

Topical anesfliesia involves die application of die anes-flietic to die surface of the skin, open area, or mucous membrane The anesthetic may be applied wifli a cotton swab or sprayed on the area This type of anesthesia may be used to desensitize the skin or mucous membrane to the injection of a deeper local anesthetic. In some instances, topical anesthetics may be applied by the nurse ... 

Breit S, Rueff F, PrzybiUa B Deep impact contact allergy after subcutaneous injection of local anesthetics. Contact Dermatitis 2001 45 296-297. Orasch CE, Helbling A, Zanni MP, Yawalkar N. Hari Y Pichler WJ T-cell reaction to local anaesthetics relationship to angioedema and urticaria after subcutaneous application-patch testing and LTT in patients with adverse reaction to local anaesthetics. Clin Exp Allergy 1999 29 1549-1554. 

In this chapter, the voltammetric study of local anesthetics (procaine and related compounds) [14—16], antihistamines (doxylamine and related compounds) [17,22], and uncouplers (2,4-dinitrophenol and related compounds) [18] at nitrobenzene (NB]Uwater (W) and 1,2-dichloroethane (DCE)-water (W) interfaces is discussed. Potential step voltammetry (chronoamperometry) or normal pulse voltammetry (NPV) and potential sweep voltammetry or cyclic voltammetry (CV) have been employed. Theoretical equations of the half-wave potential vs. pH diagram are derived and applied to interpret the midpoint potential or half-wave potential vs. pH plots to evaluate physicochemical properties, including the partition coefficients and dissociation constants of the drugs. Voltammetric study of the kinetics of protonation of base (procaine) in aqueous solution is also discussed. Finally, application to structure-activity relationship and mode of action study will be discussed briefly. 

However, local anesthetics may be helpful when abrasion accompanies the injury.39 Application of an over-the-counter antibiotic ointment containing an anesthetic may provide soothing relief, promote healing of abrasions, and prevent soft-tissue infection. Minor abrasions should be cleansed thoroughly with mild soap and water before application. More severe abrasions may require removal of debris or foreign bodies by a clinician followed by irrigation with normal saline. 

Cyclic amines (including local anesthetic drugs) and amides were among the first classes of chiral compounds investigated in the early stages of the application of macrocyclic antibiotics as chiral selectors therefore, they were screened on vancomycin [7], teicoplanin [30], and ristocetin A [33] CSPs, under RPmode systems. Cyclic imides (including barbiturates, piperidine-2,6-diones, and mephenytoin) have been separated on a vancomycin CSP [157], under NP and RP mobile phase conditions. 

The special case of the endogenous transmitter acetylcholine illustrates well the high velocity of ester hydrolysis. Acetylcholine is broken down at its sites of release and action by acetylcholinesterase (pp. 100,102) so rapidly as to negate its therapeutic use. Hydrolysis of other esters catalyzed by various esterases is slower, though relatively fast in comparison with other biotransformations. The local anesthetic, procaine, is a case in point it exerts its action at the site of application while being largely devoid of undesirable effects at other locations because it is inactivated by hydrolysis during absorption from its site of application. 

Forms of local anesthesia. Local anesthetics are applied via different routes, including infiltration of the tissue (infiltration anesthesia] or injection next to the nerve branch carrying fibers from the region to be anesthetized (conduction anesthesia of the nerve, spinal anesthesia of segmental dorsal roots), or by application to the surface of the skin or mucosa (surface anesthesia]. In each case, the local anesthetic drug is required to diffuse to the nerves concerned from a depot placed in the tissue or on the skin. 

Clinically used local anesthetics are either esters or amides. This structural element is unimportant for efficacy even drugs containing a methylene bridge, such as chlorpromazine (p. 236) or imipramine (p. 230), would exert a local anesthetic effect with appropriate application. Ester-type local anesthetics are subject to inactivation by tissue es-Ltillmann, Color Atlas of Pharmacology... 

Masters D.B. and Domb A.J., Liposphere local anesthetic timed-release for perineural site application, Pharm. Res., 15, 1038, 1998. 

The first clinical uses of a local anesthetic agent occurred in 1884, when cocaine was employed as a topical agent for eye surgery and to produce a nerve block. These events inaugurated a new era, that of regional anesthesia. New applications were developed, including spinal, epidural, and caudal anesthesia. The search for a better local anesthetic led to chemical synthesis of a number of other compounds that have more selective local anesthetic properties and few systemic side effects. 

The rate of absorption of a local anesthetic into the bloodstream is affected by the dose administered, the vascularity at the site of injection, and the specific physicochemical properties of the drug itself. Local anesthetics gain entrance into the bloodstream by absorption from the injection site, direct intravenous injection, or absorption across the mucous membranes after topical application. Direct intravascular injection occurs accidentally when the needle used for infiltration of the local anesthetic lies within a blood vessel, or it occurs intentionally when Udocaine is used for the control of cardiac arrhythmias. 

Mepivacaine hydrochloride (Carbocaine) is longer acting than lidocaine and has a more rapid onset of action (3-5 minutes). Topical application is not effective. It has been widely used in obstetrics, but its use has declined recently because of the early transient neurobehavioral effects it produces. Adverse reactions associated with mepivacaine are generally similar to those produced by other local anesthetics. It can be used with epinephrine or levonordefrin (dental use only). 

Satake et al. reported the use of a coated wire electrode sensitive to procaine and other local anesthetic cations, and their application to potentiometric determination [73]. Electrodes were constructed from a copper wire (0.8 mm diameter), coated with a PVC membrane comprising a mixture of the drug-tetraphenylborate ion-pair, dioctyl phthalate, polyvinyl chloride, and tetrahydrofuran. Potential measurement was made with respect to a Ag-AgCl reference electrode. The electrodes showed linear responses with a Nemstian slope for procaine over the concentration range investigated. The method was used for analyses of the drug in pharmaceutical preparations. 

Historically, local anesthetics have been known for many years. Cocaine, the first such agent, was isolated in 1860 and introduced for clinical application in 1884. Procaine was developed as a synthetic analog of cocaine in 1905 and lidocaine was synthesized in 1943. The development of new chemical entities as putative local anesthetics remains an ongoing activity in medicinal chemistry. 

Topical anesthesia—direct application to the skin, or a mucous membrane, of the local anesthetic in the form of a spray, cream, or gel... 

This multitude of applications has enabled local anesthetics to be used with ever-increasing effectiveness and at times to replace the considerably more dangerous use of general anesthetics. 

Combining agonists with some local anesthetics greatly prolongs the duration of infiltration nerve block the total dose of local anesthetic (and the probability of toxicity) can therefore be reduced. Epinephrine, 1 200,000, is the favored agent for this application, but norepinephrine, phenylephrine, and other agonists have also been used. Systemic effects on the heart and peripheral vasculature may occur even with local drug administration but are usually minimal. 

Nadolol is noteworthy for its very long duration of action its spectrum of action is similar to that of timolol. Timolol is a nonselective agent with no local anesthetic activity. It has excellent ocular hypotensive effects when administered topically in the eye. Levobunolol (nonselective) and betaxolol (E -selective) are also used for topical ophthalmic application in glaucoma the latter drug may be less likely to induce bronchoconstriction than nonselective antagonists. Carteolol is a nonselective 13-receptor antagonist. 

A 25-year-old woman with a 2-inch superficial laceration on her face is brought by the police to the emergency department after a street brawl. Her wound is still bleeding, but appears clean. After washing and application of pressure, the bleeding stops, and closure of the wound with sutures is planned. What local anesthetic would be appropriate for this relatively short procedure in an area where a good cosmetic result is desirable Is a vasoconstrictor appropriate ... 

Some pharmacokinetic properties of the commonly used amide local anesthetics are summarized in Table 26-2. The pharmacokinetics of the ester-based local anesthetics have not been extensively studied owing to their rapid breakdown in plasma (elimination half-life < 1 minute). Local anesthetics are usually administered by injection into dermis and soft tissues around nerves. Thus, absorption and distribution are not as important in controlling the onset of effect as in determining the rate of offset of local analgesia and the likelihood of CNS and cardiac toxicity. Topical application of local anesthetics (eg, transmucosal or transdermal) requires drug diffusion for both onset and offset of anesthetic effect. However, intracavitary (eg, intra-articular, intraperitoneal) administration is associated with a more rapid onset and shorter duration of local anesthetic effect. 

Nerve fibers differ significantly in their susceptibility to local anesthetic blockade on the basis of differences in size and degree of myelination (Table 26-3). Upon direct application of a local anesthetic to a nerve root, the smaller and C fibers are blocked first, followed by other sensory axons, and motor function is the last to be blocked. 

Sorbitan sesquioleate emulsions of petrolatum and wax are used as ointment vehicles in skin treatment. In topical applications, the inclusion of both sorbitan fatty esters and their poly(oxyethylene) derivatives modifies the rate of release and promotes the absorption of antibiotics, antiseptics, local anesthetics, vasoconstrictors, and other medications from suppositories, ointments, and lotions. Poly(oxyethylene(20)) sorbitan monooleate, also known as Polysorbate 80 (USP 23), has been used to promote absorption of ingested fats from the intestine (245). 

The method of drug administration or exposure to a poison may impart selectivity to a xenbiotic. For example, atropine can be applied directly to the eye for the dilation of the pupils. Note that eventual absorption into the blood stream from this site will cause systemic effects. Another example would be the topical (skin) application of a local anesthetic such as benzocaine. Monoclonal antibodies, which are specific for chemical functional groups, are tissue and cell-specific natural agents to which drugs can be chemically bonded. 

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... 

Applications. Various N-derivatives of amino acids (qv) are resolvable on BSA columns. These A/-amino acid derivatives include benzenesulfonyl-, phthalimido-, 5-dimethylamino-l-naphthalenesulfonyl- (DANSYL-), 2,4-dinitrophenyl- (DNP-), and 2,3,6-trinitrophenyl- (TNP-) derivatives (30). Amines such as Prilocain, (+)-2-(propylamino)-0-propiono-toluidide, a local anesthetic (Astra Pharm. Co.), are also resolved on BSA. The aromatic amino acids DL-tryptophan, 5-hydroxy-DL-tryptophan, DL-kynurenine [343-65-7], C10H12N2O3, and 3-hydroxy-m.-kynurenine [484-78-6], and dmgs such as warfarin, phenprocoumon, and benzodiazepine derivatives can be separated on BSA as well. 

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