Bupivacaine
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| Systematic (IUPAC) name |
|
(RS)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
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| Clinical data |
| Trade names |
Marcaine |
| AHFS/Drugs.com |
monograph |
Pregnancy
category |
|
| Legal status |
- AU: Prescription Only (S4)
|
Routes of
administration |
parenteral, topical |
| Pharmacokinetic data |
| Bioavailability |
n/a |
| Protein binding |
95% |
| Metabolism |
hepatic |
| Onset of action |
1-17 min |
| Biological half-life |
3.5 hours (adults)
8.1 hours (neonates) |
| Duration of action |
2-9 hr |
| Excretion |
Renal, 4–10% |
| Identifiers |
| CAS Registry Number |
38396-39-3 Y |
| ATC code |
N01BB01 |
| PubChem |
CID: 2474 |
| IUPHAR/BPS |
2397 |
| DrugBank |
DB00297 Y |
| ChemSpider |
2380 Y |
| UNII |
Y8335394RO Y |
| KEGG |
D07552 Y |
| ChEBI |
CHEBI:60789 N |
| ChEMBL |
CHEMBL1098 Y |
| Chemical data |
| Formula |
C18H28N2O |
| Molecular mass |
288.43 g/mol |
SMILES
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O=C(C1N(CCCC1)CCCC)NC2=C(C)C=CC=C2C
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InChI
-
InChI=1S/C18H28N2O/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) Y
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Key:LEBVLXFERQHONN-UHFFFAOYSA-N Y
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| N (what is this?) (verify) |
Bupivacaine (rINN) is a local anaesthetic drug belonging to the amino amide group. It is commonly marketed under various trade names, including Marcain (Astra Zeneca UK), Marcaine (Carestream Dental, Hospira Inc.), Sensorcaine (Astra Zeneca), and 'Vivacaine (Septodont). It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[1]
Contents
- 1 Medical uses
- 2 Contraindications
- 3 Adverse effects
- 3.1 Treatment of overdose
- 3.2 Pregnancy and lactation
- 4 Mechanism of action
- 5 Pharmacokinetics
- 6 Chemical structure
- 7 Developments
- 8 References
- 9 External links
Medical uses
Bupivacaine is indicated for local infiltration, peripheral nerve block, sympathetic nerve block, and epidural and caudal blocks. It is sometimes used in combination with epinephrine to prevent systemic absorption and extend the duration of action. The 0.75% (most concentrated) formulation is used in retrobulbar block.[2] It is the most commonly used local anesthetic in epidural anesthesia during labor, as well as in postoperative pain management.[3]
Contraindications
Bupivacaine is contraindicated in patients with known hypersensitivity reactions to bupivacaine or amino-amide anesthetics. It is also contraindicated in obstetrical paracervical blocks and intravenous regional anaesthesia (Bier block) because of potential risk of tourniquet failure and systemic absorption of the drug and subsequent cardiac arrest. The 0.75% formulation is contraindicated in epidural anesthesia during labor because of the association with refractory cardiac arrest.[4]
Adverse effects
Compared to other local anaesthetics, bupivacaine is markedly cardiotoxic. However, adverse drug reactions (ADRs) are rare when it is administered correctly. Most ADRs are caused by accelerated absorption from the injection site, unintentional intravascular injection, or slow metabolic degradation. However, allergic reactions can rarely occur.[4]
Clinically significant adverse events result from systemic absorption of bupivacaine and primarily involve the central nervous system (CNS) and cardiovascular system. CNS effects typically occur at lower blood plasma concentrations. Initially, cortical inhibitory pathways are selectively inhibited, causing symptoms of neuronal excitation. At higher plasma concentrations, both inhibitory and excitatory pathways are inhibited, causing CNS depression and potentially coma. Higher plasma concentrations also lead to cardiovascular effects, though cardiovascular collapse may also occur with low concentrations.[5] Adverse CNS effects may indicate impending cardiotoxicity and should be carefully monitored.[4]
- CNS: circumoral numbness, facial tingling, vertigo, tinnitus, restlessness, anxiety, dizziness, seizure, coma
- Cardiovascular: hypotension, arrhythmia, bradycardia, heart block, cardiac arrest[3][4]
Toxicity can also occur in the setting of subarachnoid injection during high spinal anesthesia. These effects include: parasthesia, paralysis, apnea, hypoventilation, fecal incontinence, and urinary incontinence. Additionally, bupivacaine can cause chondrolysis after continuous infusion into a joint space.[4]
Bupivacaine has caused several deaths when the epidural anaesthetic has been administered intravenously accidentally.[6]
Treatment of overdose
Further information: Lipid rescue
Animal evidence[7][8] indicates 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.[9][10] Plans to publicize this treatment more widely have been published.[11]
Pregnancy and lactation
Bupivacaine crosses the placenta and is a pregnancy category C drug. However, it is approved for use at term in obstetrical anesthesia. Bupivacaine is excreted in breast milk. Risks of discontinuing breast feeding versus discontinuing bupivacaine should be discussed with the patient.[4]
Mechanism of action
Bupivacaine binds to the intracellular portion of voltage-gated sodium channels and blocks sodium influx into nerve cells, which prevents depolarization. Without depolarization, no initiation or conduction of a pain signal can occur.
Pharmacokinetics
The rate of systemic absorption of bupivacaine and other local anesthetics is dependent upon the dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the preparation.[12]
- Onset of action (route and dose-dependent): 1-17 min
- Duration of action (route and dose-dependent): 2-9 hr
- Half life: neonates, 8.1 hr, adults: 2.7 hr
- Time to peak plasma concentration (for peripheral, epidural or caudal block): 30-45 min
- Protein binding: about 95%
- Metabolism: hepatic
- Excretion: renal (6% unchanged)[4]
Chemical structure
Like lidocaine, bupivacaine is an amino-amide anesthetic; the aromatic head and the hydrocarbon chain are linked by an amide bond rather than an ester as in earlier local anesthetics. As a result, the amino-amide anesthetics are more stable and less likely to cause allergic reactions. Unlike lidocaine, the terminal amino portion of bupivacaine (as well as mepivacaine, ropivacaine, and levobupivacaine) is contained within a piperidine ring; these agents are known as pipecholyl xylidines.[3]
Developments
Levobupivacaine is the (S)-(–)-enantiomer of bupivacaine, with a longer duration of action, produces less vasodilation. Durect Corporation is developing a biodegradable controlled-release drug delivery system for after surgery. It has currently completed a phase-III clinical trial.[13]
References
- ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ Lexicomp. "Bupivacaine (Lexi-Drugs)". Retrieved 20 April 2014.
- ^ a b c Miller, Ronald D. (November 2, 2006). Basics of Anesthesia. Churchill Livingstone.
- ^ a b c d e f g "Bupivacaine (Lexi-Drugs)". Retrieved 20 April 2014.
- ^ Australian Medicines Handbook. Adelaide. 2006. ISBN 0-9757919-2-3.
- ^ ABS-CBN Interactive: Filipino nurse dies in UK due to wrong use of anaesthetic
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ "bupivacaine hydrochloride (Bupivacaine Hydrochloride) injection, solution". FDA. Retrieved 20 April 2014.
- ^ 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
- RxList.com
- Drugs.com
- More on lipid rescue
- [1]
|
Local anesthetics (primarily sodium channel blockers) (N01B)
|
|
| Esters by acid |
|
Aminobenzoic
|
- Benzocaine
- Butacaine
- Butamben
- Chloroprocaine
- Dimethocaine
- Lucaine
- Meprylcaine
- Metabutethamine
- Metabutoxycaine
- Orthocaine
- Propoxycaine
- Procaine (Novocaine)
- Proxymetacaine
- Risocaine
- Tetracaine
|
|
|
Benzoic
|
- Amylocaine
- 3-(p-Fluorobenzoyloxy)tropane
- Cocaine
- Cyclomethycaine
- α-Eucaine
- β-Eucaine
- Hexylcaine
- Isobucaine
- Piperocaine
|
|
|
| Amides |
- Articaine
- Bupivacaine # / Levobupivacaine / Ropivacaine
- Butanilicaine
- Carticaine
- Dibucaine
- Etidocaine
- Lidocaine #
- Mepivacaine
- Prilocaine
- Trimecaine
|
|
| Combinations |
- Lidocaine / prilocaine
- Anesthetic / vasoconstrictor
- Iontocaine
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
Index of the peripheral nervous system
|
|
| Description |
- Anatomy
- Nerves
- cranial
- trigeminal
- cervical
- brachial
- lumbosacral plexus
- somatosensory
- spinal
- autonomic
- Physiology
- reflexes
- proteins
- neurotransmitters
- transporters
- Development
|
|
| Disease |
- Autonomic
- Congenital
- Injury
- Neoplasms and cancer
- Other
- Symptoms and signs
|
|
| Treatment |
- Procedures
- Local anesthetics
|
|
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