Levobupivacaine Bupivacaine

Synthetically, in racemization has been shown to play an important role in biologi-cal 22 chemical dynamic kinetic resolution of carbonyl compounds . Generally, if the required in siturac mization is faster than the kinetic resolution (deriva-tization step), this process can allow the conversion of a racemic substrate into a single enantiomeric product in quantitative yield This strategy has found industrial application in the synthesis of Levobupivacaine , Bupivacaine and Roxiban . ... 

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

Levobupivacaine hydrochloride (Chirocaine) is the S-enantiomer of bupivacaine. It too has long action. Animal studies show that it has less CNS and cardiac toxicity than does bupivacaine. It also is slightly more motor sparing than is bupivacaine. 

Vercauteren MP et al. Levobupivacaine combined with sufentanil and epinephrine for intrathecal labor analgesia A comparison with racemic bupivacaine. Anesth Analg 2001 93 996-1000. 

Lidocaine (lignocaine) Prilocaine Bupivacaine Levobupivacaine Ropivacaine... 

Of all the local anaesthetics available, levobupivacaine and ropivacaine have the most favourable pharmacological characteristics for use in obstetrics. They have the lowest potential for cardiotoxicity and, unlike lidocaine and prilocaine, there is little risk of cumulation when they are administered by epidural infusion at effective doses. Elimination of all amides is prolonged in the neonate, exceeding 20 h in the case of bupivacaine. 

For continuous epidural analgesia, levobupivacaine may be administered in combination with fentanyl or clonidine. Levobupivacaine has been approved in European Union states for ilio-inguinal and iliohypogastric nerve blockade in children. (See also bupivacaine, above.)... 

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-... 

Resuscitation from bupivacaine cardiovascular toxicity is extremely difficult even for experienced clinicians. Recent studies suggest that propofol can be useful in resuscitating patients acutely exposed to toxic levels of bupivacaine. The (S)-isomer, levobupivacaine, appears to have a lower propensity for cardiovascular toxicity than the racemic mixture or the (7 >isomer and has been approved for clinical use. The clinical effects of ropivacaine are similar to those of bupivacaine, but ropivacaine is allegedly associated with a lower potential for cardiovascular toxicity. Ropivacaine is available only as the ( SJ-stereoisomer, which has inherently less affinity for the cardiac sodium channel. However, both cardiac toxicity and CNS toxicity have been reported when large doses of ropivacaine were used for peripheral nerve blocks. 

Prilocaine, ropivacaine, mepivacaine, levobupivacaine Like bupivacaine ... 

The racemic compound bupivacaine, which was first synthesized by Ekenstam et al. in 1957, is an amide-type LA with a high lipophilicity, protein binding and pKa giving rise to an intermediate onset and a long duration of action. At the same time, bupivacaine has a high toxicity potential relatively often associated with convulsions and life-threatening cardivascular collapse (Moore et al., 1978). Levobupivacaine, the (S)-enantiomer of bupivacaine, has recently been developed for clinical use addressing the enantioselectivity of side-effects of bupivacaine (see below). 

Levobupivacaine, the (S)-enantiomer of bupivacaine, was developed as an alternative long-lasting local anestethic compound with a similar potency, but improved tolerability. 

In addition to levobupivacaine, ropivacaine is a new long-lasting amide-type LA that has been produced in order to address the enantioselectivity of the cardiotoxicity of bupivacaine. Ropivacaine, which is an (S)-enantiomer containing an n-propyl instead of the butyl moiety of bupivacaine, was launched in 2000. Clinical data indicate a late onset and long duration of action and the anesthetic potency of ropivacaine is comparable to that of bupivacaine (for review see McClellan and Faulds, 2000 Whiteside and Wildsmith, 2001). In animal models, the... 

Bardsley, H., Gristwood, R., Baker, H., Watson, N., Nimmo, W. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers, Br. J. Clin. Pharm. 1998, 46, 245-249. 

Liisanantti O, Luukkonen J, Rosenberg PH. High-dose bupivacaine, levobupivacaine and ropivacaine in axillary brachial plexus block. Acta Anaesthesiol Scand. 2004 48 601-606. 

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. 

MEXILETINE BUPIVACAINE, LEVOBUPIVACAINE Risk of -l BP Additive myocardial depression Particular care should be taken to avoid inadvertent intravenous administration during bupivacaine infiltration monitor PR, BP and ECG during epidural administration of bupivacaine... 

Amide compounds [lignocaine (lidocaine), prilo-caine, bupivacaine, levobupivacaine, ropivacaine] are dealkylated in the liver. 

Levobupivacaine is the S-enantiomer of racemic bupivacaine. The relative therapeutic ratio (levo-bupivacaine racemic bupivacaine) for CNS toxicity is 1.03, indicating that levobupivacaine is marginally less toxic. 

Levobupivacaine is the levorotatory isomer, 5(—)-bupiva-caine, of bupivacaine, an amide local anesthetic. 

Levobupivacaine is less cardiotoxic than racemic bupivacaine (2). In seven sheep, racemic bupivacaine caused... 

Several animal studies have shown that levobupivacaine on an equivalent dose basis is safer than bupivacaine 32-57% more levobupivacaine is required to cause death (4). In sheep, the mean lethal dose of levobupivacaine was 78% higher than that of bupivacaine the author suggested that there may be a similar trend in humans and concluded that levobupivacaine should be used in preference to bupivacaine, based on safety data alone. 

The authors proposed that some or all of the local anesthetic had been inadvertently injected intravascularly, despite negative aspiration tests. There were no cardiovascular complications, underlining the proposed greater cardiovascular safety of levobupivacaine over bupivacaine. The authors accepted that if the patient had been awake during the procedure, earlier detection of neurological symptoms might have been possible. 

Gristwood RW. Cardiac and CNS toxicity of levobupivacaine strengths of evidence for advantage over bupivacaine. Drug Saf 2002 25(3) 153-63. 

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. 

In a study in 60 anesthetized children undergoing minor subumbilical surgery caudal blocks, 0.2% ropivacaine, 0.25% racemic bupivacaine, and 0.25% levobupivacaine (all 1 ml/kg) were compared (81). All the blocks were successful in terms of intraoperative and early postoperative analgesia. Ropivacaine, but not levobupivacaine, was associated with less motor block during the first postoperative hour compared with racemic bupivacaine. However, the lower concentration of ropivacaine will have biased this result. 

In 60 women who underwent elective cesarean section under epidural anesthesia, 0.5% levobupivacaine or 0.5% bupivacaine (30 ml) were equally efficacious in terms of anesthesia (115). The incidence and severity of motor blockade, hypotension, changes in QT interval, nausea, and vomiting were not significantly different, and neither were the neonatal Apgar scores. 

Bader AM, Tsen LC, Camann WR, Nephew E, Datta S. Clinical effects and maternal and fetal plasma concentrations of 0.5% epidural levobupivacaine versus bupivacaine for cesarean delivery. Anesthesiology 1999 90(6) 1596-601. 

Levobupivacaine Isomer of bupivacaine Similar actions but fewer adverse effects... 

Local anaesthetics prevent nerve transmission by blocking sodium ion channels from the inside of the neuron. Sensory nerves that carry the stimulus of pain are the most sensitive to the actions of local anaesthetics. Accidental overdose can cause systemic effects including cardiorespiratory depression and loss of consciousness. Lidocaine is probably the most commonly used local anaesthetic. Qualified, registered podiatrists are allowed to access and administer lidocaine, bupivacaine, prilocaine, mepivacaine, levobupivacaine and ropivacaine. 

Bupivacaine is more cardiotoxic than equi-effective doses of Udocaine. Clinically, this is manifested by severe ventricular arrhythmias and myocardial depression after inadvertent intravascular administration of large doses of bupivacaine. Bupivacaine dissociates slowly during diastole, so a significant fraction of No channels at physiological heart rates remains blocked with bupivacaine at the end of diastole. Thus, the block by bupivacaine is cumulative and substantially more than would be predicted by its local anesthetic potency. Bupivacaine-induced cardiac toxicity can be very difficult to treat, and its severity is enhanced by coexisting acidosis, hypercarbia, and hypoxemia. The S-enantiomer and the racemate are equally efficacious and potent, but levobupivacaine may be less cardiotoxic. 

The piperidine ring is probably the most common heterocycle occurring in pharmaceuticals. Piperidine is often used as a secondary amine in the synthesis of drugs. The local anaesthetic bupivacaine 20 (used as the racemate or the ( S)-enantiomer levobupivacaine) is a pipecolinic acid derivative. The antihistamine bamipine 21 and the analgesic fentanyl 22 are derived from 4-aminopiperidines. The ... 

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