Bupivacaine

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File:Bupivacaine skeletal.svg
Systematic (IUPAC) name
(RS)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
Clinical data
Pronunciation /bjuːˈpɪvəkeɪn/
Trade names Marcaine, Marcain, Sensorcaine, and Vivacaine
AHFS/Drugs.com monograph
Pregnancy
category
  • AU: A
Legal status
  • AU: S4 (Prescription only)
Routes of
administration		 parenteral, topical
Pharmacokinetic data
Bioavailability n/a
Protein binding 95%
Metabolism Liver
Onset of action Within 15 min[1]
Biological half-life 3.5 hours (adults)
8.1 hours (neonates)
Duration of action 2 to 8 hr[2]
Excretion Kidney, 4–10%
Identifiers
CAS Number 38396-39-3 YesY
ATC code N01BB01 (WHO)
PubChem CID: 2474
IUPHAR/BPS 2397
DrugBank DB00297 YesY
ChemSpider 2380 YesY
UNII Y8335394RO YesY
KEGG D07552 YesY
ChEBI CHEBI:60789 N
ChEMBL CHEMBL1098 YesY
Chemical data
Formula C18H28N2O
Molecular mass 288.43 g/mol
  • O=C(C1N(CCCC1)CCCC)NC2=C(C)C=CC=C2C
  • 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) YesY
  • Key:LEBVLXFERQHONN-UHFFFAOYSA-N YesY
Physical data
Melting point 107 to 108 °C (225 to 226 °F)
 NYesY (what is this?)  (verify)

Bupivacaine, marketed under the brand name Marcaine among others, is a medication used to decrease feeling in a specific area.[1] It is used by injecting it into the area, around a nerve that supplies the area, or into the spinal canal's epidural space. It is available mixed with a small amount of epinephrine to make it last longer.[1] It typically begins working within 15 minutes and lasts for 2 to 8 hours.[1][2] Possible side effects include sleepiness, muscle twitching, ringing in the ears, changes in vision, low blood pressure, and an irregular heart rate. There are concerns that injecting it into a joint can cause problems with the cartilage. Concentrated bupivacaine is not recommended for epidural freezing. Epidural freezing may also increase the length of labor. It is a local anaesthetic of the amide group.[1] Bupivacaine was discovered in 1957.[3] It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[4] Bupivacaine is available as a generic medication and is not very expensive.[1][5] The wholesale cost of a vial is about 2.10 USD.[6]

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.[7] It is the most commonly used local anesthetic in epidural anesthesia during labor, as well as in postoperative pain management.[8]

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.[9]

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.[9]

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.[10] Adverse CNS effects may indicate impending cardiotoxicity and should be carefully monitored.[9]

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.[9]

Bupivacaine has caused several deaths when the epidural anaesthetic has been administered intravenously accidentally.[11]

Treatment of overdose

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Further information: Lipid rescue

Animal evidence[12][13] 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.[14][15] Plans to publicize this treatment more widely have been published.[16]

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.[9]

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.[17]

  • 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)[9]

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.[8]

Cost

Bupivacaine is available as a generic medication and is not very expensive.[1][5] The wholesale cost of a vial of bupivacaine is about 2.10 USD.[6]

Research

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.[18]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ 2.0 2.1 Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 6.0 6.1 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ 8.0 8.1 8.2 Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ ABS-CBN Interactive: Filipino nurse dies in UK due to wrong use of anaesthetic
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ 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

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