Bupivacaine

Bupivacaine

Systematic (IUPAC) name
(RS)-1-butyl-N-(2,6-dimethylphenyl) piperidine-2-carboxamide
Clinical data
AHFS/Drugs.com	monograph
Pregnancy cat.	A(AU)
Legal status	Prescription Only (S4) (AU)
Routes	parenteral, topical
Pharmacokinetic data
Bioavailability	n/a
Metabolism	hepatic
Half-life	3.5 hours (adults) 8.1 hours (neonates)
Excretion	Renal, 4–10%
Identifiers
ATC code	N01BB01
PubChem	CID 2474
IUPHAR ligand	2397
DrugBank	APRD00247
ChemSpider	2380 Y
UNII	Y8335394RO Y
KEGG	D07552 Y
ChEBI	CHEBI:60789 Y
ChEMBL	CHEMBL1098 Y
Chemical data
Formula	C18H28N2O
Mol. mass	288.43 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C18H28N2O.ClH.H2O/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3;;/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21);1H;1H2 Y Key:HUCIWBPMHXGLFM-UHFFFAOYSA-N Y
Y(what is this?)  (verify)

Bupivacaine (rINN) ( /bjuːˈpɪvəkeɪn/) is a local anaesthetic drug belonging to the amino amide group. AstraZeneca commonly markets it under various trade names, including Marcain, Marcaine, Sensorcaine and Vivacaine.

Indications

Bupivacaine is indicated for local anaesthesia including infiltration, nerve block, epidural, and intrathecal anaesthesia. 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

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

Adverse effects

Compared to other local anaesthetic, 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.

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

Further information: Lipid rescue

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] Schemes to publicise this use more widely have been published.^[7]

Mechanism of action

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 fibres like touch, proprioception, etc. (Myelin is non-polar / lipophilic).It should be noted, however, that bupivacaine also blocks specific potassium channels, an effect contributing to resting membrane potential depolarization.

Developments

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 is currently in Phase II.^{[citation needed]}

References

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. 

External links

• RxList.com
• Drugs.com
• More on lipid rescue