Bupivacaine, injectable

Parenterals are administered to the body by injection. They must be sterile, nonpyro-genie, and particulate-free. Examples of compoimded parenterals include high-dose analgesics for patient controlled analgesia (morphine sulfate 50 mg/mL), antiemetic injections, fentanyl and bupivacaine injections for ambulatory pump reservoirs, oncology combinations, and others (Table 10). 

Alsarraf R, Sie KC. Brain stem stroke associated with bupivacaine injection for adenotonsiUectomy. Otolaryngol Head Neck Surg 2000 122(4) 572-3. 

Intravenously injected bupivacaine is more toxic than i.v. etidocaine (32), but in epidural anaesthesia no difference in severity of side effects was found when the 2 were compared under double-blind conditions (33 -). In another double-blind cross-over study in 11 volunteers, the psychomotor performance after 2.6 mg/kg body weight etidocaine given intramuscularly was the same as after 1.3 mg/kg bupivacaine injected intramuscularly. These doses were chosen because they were considered to be equi-potent (34). 

R = / -C H ), in low doses, exhibits the former behavior and is used primarily as an extradural agent in obstetrics. The lowest effective extradural concentration of etidocaine (21, X = CH, R = R = 2H, R = / -C H ), however, shows both adequate sensory and profound motor blockade so that it is useful in surgical situations where maximum neuromuscular blockade is necessary. In an isolated nerve preparation, bupivacaine blocks unmyelinated C fibers which are mainly responsible for pain perception at a much greater extent than the myelinated A fibers which carry motor impulses. It is postulated that absorption of bupivacaine by the vasculature at the site of injection, combined with the slow diffusion of this agent, results in an insufficient amount of the drug penetrating the large A fibers to cause motor conduction blockade. Clinically, motor block can be observed in some procedures. 

Z. Yu and D. Westerlund, Direct injection of large volumes of plasma in a columnswitching system for the analysis of local anaesthetics , II. Determination of bupivacaine in human plasma with an alkyl-diol silica precolumn , ]. Chromatogr. A 725 149-155 (1996). 

The amide local anaesthetic lidocaine may also be used as an antianhythmic for ventricular tachycardia and exra-systoles after injection into the blood circulation. Drugs with high lipid solubility such as bupivacaine cannot be used for these purposes because their prolonged binding to the channel may induce dysrhythmias or asystolic heart failure [3]. Systemically applied lidocaine has also been used successfully in some cases of neuropathic pain syndromes [4]. Here, electrical activity in the peripheral nervous system is reduced by used-dependent but incomplete sodium channel blockade. 

Fentanyl citrate—bupivacaine hydrochloride-epinephrine hydrochloride injection (100 mL)... 

Bupivacaine is an anaesthetic with a slow onset but a long duration of action. It is indicated for continuous epidural analgesia in labour. Xylocoine is the proprietary preparation of lidocaine (lignocoine). Lidocoine injections ore used in dentistry. 

Four analysts obtain the following data for a spectrophotometric analysis of an injection containing the local anaesthetic bupivacaine. The stated content of the injection is 0.25% weight in volume (w/v). 

Adrenaline in bupivacaine/adrenaline injection is assayed by complex formation with iron (II). 20 ml of the injection is mixed with 0.2 ml of reagent and 2 ml of buffer and a reading is taken in a 4 cm pathlength cell. A reading of a solution containing 5.21 pg/ml of adrenaline is taken under the same conditions. 

Dimethylaniline is both a manufacturing impurity in bupivacaine and since it is formulated in injections a possible breakdown product, although hydrolysis of amides is much slower than hydrolysis of esters. The BP uses a spectrophotometric method to assay for this impurity but GC provides a more sensitive and specific method for this determination. 

The GC trace obtained from injection of a 10% w/v solution of bupivacaine free base extracted from an injection gave the trace shown in Figure 11.21. It is apparent from comparison with a standard for dimethylaniline that there is < 0.1 % of the impurity present although a number of other peaks due to excipients or impurities can be seen in the GC trace. 

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. 

Ester and amide local anaesthetics differ in the manner, site and rate of metabolism. There is little relation between the elimination of local anaesthetics and their duration of action. Amethocaine has a prolonged action due to its high affinity for nerve tissue despite being rapidly removed from plasma. Bupivacaine can be detected in the plasma many hours after its effects have worn off due to continuing absorption from the site of injection. The renal excretion of unchanged local anaesthetics is minimal. 

Parenteral 10 mg/mL lidocaine plus 3.75 mg/mL bupivacaine for injection Lidocaine and prilocaine eutectic mixture (EMLA cream)... 

Clinical use Because of its long duration of action, bupivacaine is indicated for long surgical anesthesia where a considerable amount of postoperative pain is expected such as dental and oral surgeries. Infiltration using a 0.25 % solution of bupivacaine produces sensory anesthesia with an onset of 2 to 5 min and a duration of 2 to 4 h or greater (Tetzlaff, 2000). A nerve conduction block with a duration of between 4 to 8 h and occasionally up to 24 h is achieved with injection of 0.5 to 0.75 %... 

Cobb Z, Sellergren B, Andersson LI (2007) Water-compatible molecularly imprinted polymers for efficient direct injection on-line solid-phase extraction of ropivacaine and bupivacaine from human plasma. Analyst 132(12) 1262—1271... 

T. G. Venkateshwaran and J. T. Stewart, HPLC determination of morphine-hydromorphone-bupivacaine and morphine-hydromor-phone-tetracaine mixtures in 0.9% sodium chloride injection, J. Liquid Chromatogr., 18 565 (1995). 

Kalso, E. (1983). Effects of intrathecal morphine, injected with bupivacaine, on pain after orthopaedic surgery. Br.J. Anaesth. 55, 415-422. 

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... 

---