Anesthetics local bupivacaine lidocaine

Local Anesthetics. Local anesthetics used in anesthesiology are currently amide derivatives (lidocaine, mepivacaine, prilocaine, bupivacaine, levobupivacaine. 

The action of several anesthetics has also been associated with a modulation of K+ channels. In addition to blocking Na+ currents in spinal neurones of the superficial dorsal horn the local anesthetics bupivacaine, lidocaine and mepivacaine reduce transient, A-type K+ currents in these cells whereas delayed rectifier K+ currents proved to be resistant (Olschewski et al., 1998). Since the A-type K+ current determines the frequency pattern of repetitively firing neurones (Hille, 2001) their suppression in dorsal... 

A need was seen for a synthetic and less toxic anesthetic. In 1905, Procaine was synthesized and became the prototype for synthesized anesthetics for the next 50 years. In 1948, Lidocaine was developed and is now the most commonly used local anesthetic. Other synthesized local anesthetics include bupivacaine and tetracaine. 

Masters and Domb [250] reported on an injectable drug delivery system that uses liposomes [251] to release the local anesthetic, bupivacaine, from a liposomal matrix that is both biodegradable and biocompatible to produce SLAB. Bupivacaine due to its minimum vasodilating properties was preferred to other local anesthetics (e.g., lidocaine) allowing the released drug to remain at the site of injection longer [252]. Lipospheres are an aqueous microdispersion of water insoluble, spherical microparticles (0.2 to 100 pm in diameter), each consisting... 

Highly hpid-soluble, extensively protein-bound, highly potent local anesthetics, such as tetracaine, bupivacaine, and etidocaine, are much more cardiotoxic than less lipid-soluble, protein-bound, and potent local anesthetics, such as lidocaine and prilocaine. 

Some distinction must be made between the main groups of local anesthetics as to the frequency of complications. Hypersensitivity reactions, for example, are relatively less common with the aminoamides, such as bupivacaine, cinchocaine, etidocaine, lidocaine, mepivacaine, prilocaine, and ropivacaine, than with the amino-esters. However, the systemic toxic effects of individual local anesthetics differ bupivacaine, cinchocaine, and tetracaine are the most toxic. Furthermore, the individual characteristics of the patient (for example age, sex, body weight, and cardiac, renal, and hepatic function) are important (SEDA-17,134). 

Opioids potentiate the analgesic effect of neuraxial local anesthetics, with minimal adverse effects (SEDA-18,141) (SEDA-20, 121) (SEDA-22, 135), as shown in several studies with clonidine, fentanyl, morphine, or pethidine as the systemic or neuraxial analgesic, and bupivacaine, lidocaine, and ropivacaine as the local anesthetic. The benefits have been shown in relief of long-term pain and postoperative pain, in adults and children (SEDA-18, 141) (SEDA-18,146). 

A 45-year-old patient is to have reconstrucdve surgery on a hand that was recently injured in an accident. The anesthesiologist plans to use regional anesthesia of the arm for a fairly long procedure. The amide-t3 pe local anesthetic with the longest duration of action is (A) Cocaine Bupivacaine Lidocaine Procaine Tetracaine... 

Good relationships between the retention in MLC and some biological activities of local anesthetics (bupivacaine, lidocaine, mepiva-caine, prilocaine, procaine and tetracaine), such as anesthetic potency, concentration of compound that produces an effect similar to a reference concentration of cocaine, duration of the action, toxicity and time taken to eliminate half the drug present in the body, have also b n reported [24]. Some anesthetic actions of barbiturates also correlated well with the retention minimum effective hypnotic dose in rabbits, molar drug concentration necessary to reduce cell division, and molar drug concentration required to reduce 50% the inhibition of oxygen respiration on the brain of a rat in vitro [25],... 

Spinal anesthesia Spinal anesthesia is the introduction of local anesthetics directly into the spinal fluid, which causes a sympathetic blockage, or loss of feeling as well as muscle relaxation resulting from the interaction of anesthetic with every spinal nerve tract. This method is used during major surgical interventions. As a rule, lidocaine, mepivacaine, and bupivacaine are used for this purpose. 

Epidural anesthesia This term is understood to be an introduction of local anesthetic into the spinal cord membrane of the intervertebral space. It is used during obstetrical and gynecological interventions that do not require a fast development of anesthesia. Drugs such as lidocaine, mepivacaine, bupivacaine, ethidocaine, and chloroprocaine are used for this purpose. 

Amide-type agents include articaine, lidocaine, bupivacaine, prilocaine, mepivacain and ropiva-caine. These are metabolized in the liver by microsomal enzymes with amidase activity. The amide group is preferred for parenteral and local use. If by accident rapidly administered intravascularly these agents, especially bupivacaine but also lidocaine, can produce serious and potentially lethal adverse effects including convulsions and cardiac arrest. They can more easily accumulate after multiple administrations. Intravenous lidocaine is sometimes used for regional anesthesia, for infiltration procedures, for the induction of nerve blockade and for epidural anesthesia. However, it is also used as an antiarrhythmic. Bupivacaine is a long-acting local anesthetic used for peripheral nerve blocks and epidural anesthesia. 

Answer Bupivacaine use for local anesthesia of this type is very safe and commonly done. However, SOMETIMES inadvertent vascular injection results in a large amount of anesthetic in the systemic circulation. Because the heart is beating, the excitable tissue in the heart is being depolarized repetitively. Local anesthetics bind to rapidly depolarizing tissues more than tissues at rest (frequency-dependent block). Also, bupivacaine has a long duration of action because of its long residence time at receptors (sodium channel). Thus, this combination of factors contributed to the catastrophic outcome of this case. Had the same case involved lidocaine, the resuscitation would have likely been successful. 

The local anesthetics can be broadly categorized on the basis of the chemical nature of the linkage contained within the intermediate alkyl chain group. The amide local anesthetics include lidocaine (7.5), mepivacaine (7.6), bupivacaine (7.7), etidocaine (7.8), prilocaine (7.9), and ropivacaine (7.10) the ester local anesthetics include cocaine (7.11), procaine (7.12), benzocaine (7.13), and tetracaine (7.14). Since the pharmacodynamic interaction of both amide and ester local anesthetics with the same Na" channel receptor is essentially idenhcal, the amide and ester functional groups are bioisosterically equivalent. However, amide and ester local anesthetics are not equal from a pharmacokinetic perspective. Since ester links are more susceptible to hydrolysis than amide links. 

Local anesthetics have weak direct neuromuscular blocking effects that are of little clinical importance. However, their effects on cardiac cell membranes are of major clinical significance, and some local anesthetics are widely used as antiarrhythmic agents (eg, lidocaine) (see Chapter 14) at concentrations lower than those required to produce nerve block. Others of the same amide class (eg, bupivacaine, ropivacaine) can cause lethal arrhythmias if high plasma concentrations are inadvertently achieved. 

The choice of local anesthetic for infiltration, peripheral nerve blocks, and central neuraxis (spinal/epidural) blockade is usually based on the duration of action required. Procaine and chloroprocaine are short-acting lidocaine, mepivacaine, and prilocaine have an intermediate duration of action and tetracaine, bupivacaine, levobupivacaine, and ropivacaine are long-... 

The tests allow judgement of the propensity of local anesthetics to induce symptoms of hepatic porphyria. The local anesthetics lidocaine, bupivacaine, etido-caine, mepivacaine, prilocaine and pyrocaine belong to this group, but procaine, butacaine, oxybuprocaine, proxymethacaine and tetracaine had no (or very slight) porphyrinogenic effect. 

Cardiovascular effects due to enhanced sympathetic activity include tachycardia, increased cardiac output, vasoconstriction, and increased arterial pressure. Myocardial infarction is the most common adverse cardiac effect (43), and there is an increased risk of myocardial depression when amide-type local anesthetics, such as bupivacaine, levobupivacaine, lidocaine, or ropivacaine are administered with antidysrhythmic drugs. 

Bupivacaine is a long-acting aminoamide local anesthetic with significantly more systemic toxicity than lidocaine. 

Infusions of 0.25% bupivacaine into pig coronary arteries caused ventricular fibrillation at lower rates of infusion than 0.25% bupivacaine with 1% lidocaine (10). The lidocaine/bupivacaine mixture did not have a greater myocardial depressant effect than bupivacaine alone. The authors suggested that when regional anesthesia requires high doses of local anesthetics, bupivacaine should not be used alone but in a mixture with lidocaine, and that lidocaine should be useful in the management of bupivacaine-induced ventricular fibrillation. 

In the elderly, some local anesthetics (including lidocaine and bupivacaine) have longer durations of action (18). 

The cardiovascular system is more resistant to the toxic effects of local anesthetics than the nervous system. Mild circulatory depression can precede nervous system toxicity, but seizures are more likely to occur before circulatory collapse. The intravenous dose of lidocaine required to produce cardiovascular coUapse is seven times that which causes seizures. The safety margin for racemic bupivacaine is much lower. The stereospecific levorotatory isomers levobupivacaine and ropivacaine are less cardiotoxic, and have a higher safety margin than bupivacaine, but not lidocaine in the case of ropivacaine this may be at the expense of reduced anesthetic potency (14,15). Toxicity from anesthetic combinations is additive. 

Incidence The incidence of transient radicular irritation varies depending on the local anesthetic used, its baricity, and its concentration. It has been reported to be as high as 37% in patients who receive 5% lidocaine. In a prospective study of 303 parturients undergoing intrathecal anesthesia using 0.75% hyperbaric bupivacaine or 5% lidocaine there were no cases of transient radicular irritation after lidocaine (227). This is remarkable, as significantly more procedures were performed in the lithotomy position in the lidocaine group the authors wondered if such a low incidence of transient radicular irritation could have been explained by their use of a 1 1 dilution of lidocaine with cerebrospinal fluid. 

In a careful meta-analysis, 29 randomized, controlled studies of the incidence of transient radicular irritation were identified (243). Lidocaine and mepivacaine were identified as the two local anesthetics that most commonly cause transient radicular irritation, while prilo-caine, bupivacaine, and ropivacaine had the lowest incidences. Owing to insufficient data, definitive statements could not be made about the effects of the baricity of the local anesthetic, the concentration, and the effect of vasoconstrictors, although all these factors seemed not to be relevant. With regard to intrathecal ropivacaine, the incidence in the formal studies was zero. However, there has been one previous report after intrathecal administration, and one report of transient radicular irritation following epidural anesthesia with ropivacaine the symptoms resolved within 24 hours (244). 

The high baricity of the local anesthetic solutions was thought to be chiefly responsible for transient radicular irritation. However, isobaric local anesthetics have also been implicated commonly the concentrations are 2% or greater. From comparisons of 2 and 5% hyperbaric and isobaric lidocaine and hyperbaric 0.5% bupivacaine, it seems more likely that high concentrations of local anesthetic solutions are responsible for transient radicular irritation rather than the osmolarity of the solutions (247-249). That the concentration of lidocaine is not a contributory factor to transient radicular irritation has been shown in 109 patients who received hyperbaric spinal lidocaine 50 mg, as a 2, 1, or 0.5% solution (250). The incidence of transient radicular irritation did not differ (16, 22, and 17% respectively). 

The endothelial toxicity of local anesthetics has been assessed in pigs, as this might be relevant to the safety of agents given by intracameral injection (335). Lidocaine, mepivacaine, and prilocaine were safe, while bupivacaine in clinically effective concentrations resulted in significant cell reduction. 

Radwan lA, Saito S, Goto F. The neurotoxicity of local anesthetics on growing neurons a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine. Anesth Analg 2002 94(2) 319-24. 

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