Bupivacaine

Bupivacaine, which is more potent than lidocaine, has a prolonged duration of action. 

Therapeutic Function Local anesthetic Chemical Name dl-1-butyl-2, 6 -pipecoloxylidide Common Name — 

Trade Name Manufacturer Country Year Introduced 

6-Dimethylaniline Nitrosyl Chloride Formic Acid Diethyl Malonate Zinc Powder n-8utylbromide  

121 parts by weight of 2,6-xylidine are heated with 400 parts of diethylmalonate at 160°C for 1 hour, and the alcohol formed by the reaction is allowed to distill off. Thereafter the reaction mass Is cooled to 80°C, and 500 parts of alcohol are added. After cooling the dixylldide is sucked off, and the alcohol solution with malonic ester monoxylldide is poured into 2,000 parts of water. The monoxylldide precipitates, is filtered off and washed with water, and recrystallized in diluted alcohol. NItrosation thereafter takes place by dissolving the dried monoxylldide in chloroform and by introducing nitrosyl chloride at 0°C until the nitrosation is completed. The isonitrosomalonic ester xylidide is filtered off and dried. Thereafter the reduction takes place with zinc powder and formic acid at 90°-100°C. 

The formic acid Is distilled off, and the remainder dissolved in warm benzene and washed with a bicarbonate solution to a neutral reaction. After the benzene has been distilled off, the aminomalonic ester xylidide is obtained. This Is treated with an equal quantity of sodium ethylate and boiled with twice the theoretical quantity of tetramethylene bromide in absolute alcohol. 

After 6 hours of boiling, the sodium bromide formed is separated, and the mixture is steam-distilled in order to remove the excess of tetramethylene bromide. The remaining oil, which mainly consists of delta-bromobutylaminomalonic ester xylidide is separated from the water and boiled with 3 parts of concentrated hydrochloric acid for 3 hours. Thereafter carbonfiltering and evaporation to dryness under vacuum takes place. The residue is dissolved in water, and the pH adjusted with sodium hydroxide to 5.5. The solution is extracted twice with ether, and the water is made strongly alkaline with sodium hydroxide. 

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Another clinical consideration is the abiUty of local anesthetic agents to effect differential blockade of sensory and motor fibers. In surgical procedures such as obstetrics or postoperative pain rehef, an agent which produces profound sensory block accompanied by minimal motor block is desirable. On the other hand some procedures such as limb surgery require both deep sensory and motor blockade. In clinical practice, bupivacaine ( 22,... 

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. 

Chloroprocaine hydrochloride [3858-89-7] is characterized by low potency, rapid onset, short duration of action, and low systemic toxicity. It is indicated for infiltration anesthesia at 1—2% and for extradural anesthesia at 2—3% when short surgical procedures are performed under regional anesthesia. Chloroprocaine may be mixed with long duration agents such as bupivacaine (22, R = n-Q [) to afford a more rapid onset and shorter duration of action than bupivacaine alone. 

Anesthetic Agents Under Development. Ropivacaine (AL-381) (22, R = similar in stmcture to mepivacaine and bupivacaine, has... 

T. Arvidsson and E. Eklund, Determination of free concenti ation of ropivacaine and bupivacaine in blood plasma by ultrafilti ation and coupled-column liquid cliromatogra-phy , 7. Chromatogr. B 668 91-98 (1995). 

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). 

N-tert-Butyl-2-(5-benzyloxy-6-hydroxy-methyl-2-pyr idyl)-2-hydroxy acetamide Pirbuterol Butyl bromide Bufexamac Bupivacaine Fenipentol sec-Butyl bromide... 

N, N-Diethylethylenediamine Tiapride Diethyl ketone Molindone Diethyl maleate Malathion Diethyl malonate Bupivacaine Kebuzone... 

Fluoro uracil mercury Tegafur Formaldehyde Biperiden Bronopol Cortivazol Edetate disodium Glaziovine Hexetidine Meptazinol Metampicillin sodium Methylol riboflavin Nifurfoline Nifurtoinol Noxytiolin Oxymetazoline HCI Phenindamine tartrate Pipebuzone Thihexinol Timonacic sodium Triclobisonium chloride T romethamine Tyloxapol Formamide Cimetide Primidone Protriptyline Razo xane Spiperone Formic acid Bupivacaine... 

Manuril - Hydrochlorothiazide Manypren - (buprofen Maolate - Chlorphenesin carbamate Marax - Hydroxyzine HCI Marbate - Meprobamate Marcain Bupivacaine Marcaina - Bupivacaine... 

Patients who do not obtain sufficient symptomatic relief from other treatments may use lidocaine, benzonatate, bupivacaine topically or mexiletine orally. 

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. 

Clarkson CW, Hondeghem LM (1985) Mechanism for bupivacaine depression of cardiac conduction fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology 62 396-405... 

Another topical anesthetic, similar to benzocaine, is lidocaine, which is used to relieve the pain of shingles (herpes zoster) infections. Lidocaine is called an amide anesthetic, because it is not an ester (the alcohol is replaced by an amide, the nitrogen group). Amide anesthetics are metabolized by the liver, and are less prone to cause allergic reactions. If an anesthetic has the letter i in the prefix (lidocaine, prilocaine, bupivacaine), it is an amide anesthetic. 

Some other anesthetics with similar structures are prilocaine, tetracaine, ropivacaine, bupivacaine, chloroprocaine, and mepivacaine ... 

D Bupivacain (Rhone- GB Marcain (Astra) Marcaina iperbarica... 

C4H,jBr 109-65-9) see Bufexamac Bupivacaine Butylscopolammonium bromide Oxybuprocaine Tetracaine sec-butyl bromide... 

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