Local anesthetic side effects

Benzonatate [104-31 ] (46) is a unique compound which appears to have both central and peripheral antitussive effects. Stmcturally it is a derivative of ji)-aminoben2oic acid and contains a long poly(ethylene glycol) side chain. The peripheral effects ate the result of local anesthetic action on the pulmonary stretch receptors. Clinical activity was first reported in 1955 (65). 

Ziconotide is a non-opioid, non-NSAID, non-local anesthetic used for the amelioration of chronic pain. In December 2004 the FDA approved ziconotide for intrathecal administration. The drug is derived from a marine snail toxin. Its mechanism of action has not yet been elucidated. Due to serious side effects or lack of efficacy when delivered through more conventional routes ziconotide must be administered in-trathecally. It s use is considered appropriate only for management of severe chronic pain in patients for whom intrathecal therapy is indicated. 

Dextromethorphan hydrobromide is the D-isomer of levorphanol. It lacks CNS activity but acts at the cough center in the medulla to produce an antitussive effect. It is half as potent as codeine as an antitussive. Anecdotal reports of abuse exist, but studies of abuse potential are lacking. It has few side effects but does potentiate the activity of monoamine oxidase inhibitors, leading to hypotension and infrequently coma. Dextromethorphan is often combined in lozenges with the local anesthetic benzocaine, which blocks pain from throat irritation due to coughing. 

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 development of newer agents continues because it is relatively easy to synthesize chemicals with local anesthetic properties. Unfortunately, it is difficult to reduce the toxicity of these compounds because the common side effects of local anesthetics represent extensions of their therapeutic effects. New research into the mechanisms of local anesthetic-induced cardiac and spinal toxicity and identification of alternative drug targets for spinal analgesia (eg, opioid receptors, [Pg.560]

Bupivacaine is a long-acting local anesthetic drug and has a high risk of side-effects which are enantio-selective and mainly associated with the (R)-enantio-mer... 

Anesthetics prevent neurons from transmitting sensations to the brain. Local anesthetics are applied either topically to numb the skin or by injection to numb deeper tissues. These mild anesthetics are useful for minor surgical or dental procedures. As described earlier, cocaine was the first medically used local anesthetic. Others having fewer side effects soon followed, such as the ones shown in Figure 14.39 on page 508. In general, molecules that... 

The ease of application, the minimization of systemic side effects, and the increased drug penetration directly into the target region resulted in extensive clinical use of iontophoresis mainly in the transdermal field. This technique has been utilized for administration of local anesthetics [2-5], sweat chloride testing in cystic fibrosis patients by transcutaneous delivery of pilocarpine [6,7], administration of vidarabine to patients with herpes orolabialis [8], fluoride administration to patients with hypersensitive dentin [9,10], and gentamicin delivery for the management of burned ears [11],... 

PCA allows the patient to self-administer a small amount of analgesic medication on a relatively frequent basis. This technique has been used to administer drugs such as opioids and local anesthetics. PCA can often provide better pain control with smaller quantities of the drug and a lower incidence of side effects. The patient is allowed to self-administer a small dose of the drug by pressing a button that is connected to some type of pump. These PCA pumps vary in cost, level of sophistication, and location (external versus surgically implanted), but all pumps... 

A frequently cited example of an important natural-product-derived drag is the neuromuscular blocker d-tubocurarine, derived from the South American plant curare, which was used by South American Indians as an arrow poison (see Chapter 26). Tubocurarine led to the development of decamethonium, which, although structurally dissimilar to tubocurarine, was nevertheless synthesized based on the then prevalent presumption that tubocurarine contained two quaternary nitrogens. Similarly, synthetic local anesthetics, such as lidocaine, benzocaine, and dibucaine, were synthesized to mimic the nerve-blocking effect of cocaine, a natural alkaloid obtained from the leaves of Coca eroxylum, but without the adverse side effects that have led to its abuse. 

An overdosage of local anesthetics can produce dose-dependent central nervous system (CNS) side effects such as insomnia, visual and auditory disturbances, nystagmus, shivering, tonic-clonic convulsions, and finally fatal CNS depression. The initial CNS excitation and convulsions may be brought under control by diazepam or thiopental. 

The local anesthetic lidocaine provides significant relief of neuropathic pain in the clinic when administered systemically at subanesthetic doses. In several placebo-controlled studies, intravenous infusions of lidocaine significantly reduced neuropathic pain at plasma concentrations of 1.5-5 pgmL 1 [59-61]. Lightheadedness is a common side effect at therapeutic doses, whereas cardiac depression is associated with plasma concentrations of 20-25 xgmL 1. A transdermal formulation of lidocaine is approved in the United States for the treatment of postherpetic neuralgia [62]. Orally available state-dependent Nayl blockers have shown efficacy in the clinic when appropriate plasma concentrations are achieved. 

In some types of rhythm disorders, antiar-rhythmics of the local anesthetic, Na+-channel blocking type are used for both prophylaxis and therapy. These substances block the Na+ channel responsible for the fast depolarization of nerve and muscle tissues. Therefore, the elicitation of action potentials is impeded and impulse conduction is delayed. This effect may exert a favorable influence in some forms of arrhythmia, but can itself act arrhythmogenically. Unfortunately, antiarrhythmics of the local anesthetic, Na+-channel blocking type lack suf -cient specificity in two respects (1) other ion channels of cardiomyocytes, such as K1 and Ca+ channels, are also affected (abnormal QT prolongation) and (2) their action is not restricted to cardiac muscle tissue but also impacts on neural tissues and brain cells. Adverse effects on the heart include production of arrhythmias and lowering of heart rate, AV conduction, and systolic force. CNS side effects are manifested by vertigo, giddiness, disorientation, confusion, motor disturbances, etc. 

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