Bupivacaine

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Bupivacaine
Systematic (IUPAC) name
(RS)-1-butyl-N-(2,6-dimethylphenyl)
piperidine-2-carboxamide
Clinical data
Trade namesMarcaine
AHFS/Drugs.commonograph
Pregnancy cat.A (AU)
Legal statusPrescription Only (S4) (AU)
Routesparenteral, topical
Pharmacokinetic data
Bioavailabilityn/a
Metabolismhepatic
Half-life3.5 hours (adults)
8.1 hours (neonates)
ExcretionRenal, 4–10%
Identifiers
CAS number2180-92-9 YesY
ATC codeN01BB01
PubChemCID 2474
IUPHAR ligand2397
DrugBankDB00297
ChemSpider2380 YesY
UNIIY8335394RO YesY
KEGGD07552 YesY
ChEBICHEBI:60789 N
ChEMBLCHEMBL1098 YesY
Chemical data
FormulaC18H28N2O 
Mol. mass288.43 g/mol
 N (what is this?)  (verify)
 
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Bupivacaine
Systematic (IUPAC) name
(RS)-1-butyl-N-(2,6-dimethylphenyl)
piperidine-2-carboxamide
Clinical data
Trade namesMarcaine
AHFS/Drugs.commonograph
Pregnancy cat.A (AU)
Legal statusPrescription Only (S4) (AU)
Routesparenteral, topical
Pharmacokinetic data
Bioavailabilityn/a
Metabolismhepatic
Half-life3.5 hours (adults)
8.1 hours (neonates)
ExcretionRenal, 4–10%
Identifiers
CAS number2180-92-9 YesY
ATC codeN01BB01
PubChemCID 2474
IUPHAR ligand2397
DrugBankDB00297
ChemSpider2380 YesY
UNIIY8335394RO YesY
KEGGD07552 YesY
ChEBICHEBI:60789 N
ChEMBLCHEMBL1098 YesY
Chemical data
FormulaC18H28N2O 
Mol. mass288.43 g/mol
 N (what is this?)  (verify)

Bupivacaine (rINN) /bjuːˈpɪvəkn/ is a local anaesthetic drug belonging to the amino amide group. It is commonly marketed under various trade names, including Marcain, Marcaine (Carestream Dental), Sensorcaine (Astra Zeneca) and Vivacaine (Septodont).

Indications[edit]

Bupivacaine is indicated for local anesthesia including infiltration, nerve block, epidural, and intrathecal anesthesia. Bupivacaine often is administered by epidural injection before total hip arthroplasty. It also is commonly injected to surgical wound sites to reduce pain for up to 20 hours after the surgery. Sometimes, bupivacaine is co-administered with epinephrine to prolong the duration of its action, fentanyl for epidural analgesia, or glucose.

Contraindications[edit]

Bupivacaine is contraindicated for intravenous regional anaesthesia (IVRA) because of potential risk of tourniquet failure and systemic absorption of the drug.

Adverse effects[edit]

Compared to other local anaesthetics, bupivacaine is markedly cardiotoxic. However, adverse drug reactions (ADRs) are rare when it is administered correctly. Most ADRs relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, however allergic reactions can rarely occur.[citation needed]

Systemic exposure to excessive quantities of bupivacaine mainly result in central nervous system (CNS) and cardiovascular effects – CNS effects usually occur at lower blood plasma concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. CNS effects may include CNS excitation (nervousness, tingling around the mouth, tinnitus, tremor, dizziness, blurred vision, seizures) followed by depression (drowsiness, loss of consciousness, respiratory depression and apnea). Cardiovascular effects include hypotension, bradycardia, arrhythmias, and/or cardiac arrest – some of which may be due to hypoxemia secondary to respiratory depression.[1]

Bupivacaine has caused several deaths when the epidural anaesthetic has been administered intravenously accidentally.[2]

Treatment of overdose: lipid rescue[edit]

There is animal evidence[3][4] that Intralipid, a commonly available intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anaesthetic overdose, and human case reports of successful use in this way.[5][6] Plans to publicize this treatment more widely have been published.[7]

Mechanism of action[edit]

Bupivacaine binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization. Since pain transmitting nerve fibres tend to be thinner and either unmyelinated or lightly myelinated, the agent can diffuse more readily into them than into thicker and more heavily myelinated nerve fibers such as those involved in touch and proprioception. (Myelin is non-polar / lipophilic). Bupivacaine also blocks specific potassium channels, an effect contributing to resting membrane potential depolarization.

Developments[edit]

Levobupivacaine is the (S)-(–)-enantiomer of bupivacaine, with a longer duration of action and produces less vasodilation. Durect Corporation is developing a biodegradable controlled-release drug delivery system for post surgery. It has currently completed a Phase III clinical trial.[8]

References[edit]

  1. ^ Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
  2. ^ ABS-CBN Interactive: Filipino nurse dies in UK due to wrong use of anaesthetic
  3. ^ Weinberg, GL, VadeBoncouer, T, Ramaraju, GA, Garcia-Amaro, MF, Cwik, MJ. (1998). "Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats". Anesthesiology 88 (4): 1071–5. doi:10.1097/00000542-199804000-00028. PMID 9579517. 
  4. ^ Weinberg, G, Ripper, R, Feinstein, DL, Hoffman, W. (2003). "Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity". Regional Anesthesia and Pain Medicine 28 (3): 198–202. doi:10.1053/rapm.2003.50041. PMID 12772136. 
  5. ^ Rosenblatt, MA, Abel, M, Fischer, GW, Itzkovich, CJ, Eisenkraft, JB (July 2006). "Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest.". Anesthesiology 105 (1): 217–8. doi:10.1097/00000542-200607000-00033. PMID 16810015. 
  6. ^ Litz, RJ; Popp, M; Stehr, S N; Koch, T. (2006). "Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion". Anaesthesia 61 (8): 800–1. doi:10.1111/j.1365-2044.2006.04740.x. PMID 16867094. 
  7. ^ Picard, J, Meek, T (February 2006). "Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob.". Anaesthesia 61 (2): 107–9. doi:10.1111/j.1365-2044.2005.04494.x. PMID 16430560. 
  8. ^ Bupivacaine Effectiveness and Safety in SABER™ Trial (BESST); http://clinicaltrials.gov/ct2/show/NCT01052012 ClinicalTrials.gov processed this record on February 29, 2012.

External links[edit]