Chemistry:Chloroprocaine

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Short description: Local anaesthetic drug
Chloroprocaine
Chloroprocaine.svg
Clinical data
Trade namesNesacaine, Iheezo, others
AHFS/Drugs.comMicromedex Detailed Consumer Information
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC13H19ClN2O2
Molar mass270.76 g·mol−1
3D model (JSmol)
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Chloroprocaine (trade name Nesacaine, Nesacaine-MPF) (often in the hydrochloride salt form as the aforementioned trade names) is a local anesthetic given by injection during surgical procedures and labor and delivery. Chloroprocaine vasodilates; this is in contrast to cocaine which vasoconstricts. Chloroprocaine is an ester anesthetic.[3]

Medical uses

Chloroprocaine is used for regional anaesthesia including spinal anaesthesia, caudal anaesthesia and epidural anesthesia.[4][5]

It is also indicated for local anaesthesia including brachial plexus block, cervical nerve block, occipital nerve block. mandibular nerve block or maxillary nerve block for dental anesthesia, ophthalmic anesthesia via infraorbital nerve block, ulnar nerve block, paravertebral block, intercostal nerve block, sciatic nerve block, stellate ganglion block, lumbar sympathetic block and interdigital block.[5]

It is also used for obstetric anesthesia including pudendal nerve block and paracervical block.[5]

Chloroprocaine is also indicated for ocular surface anesthesia.[2]

Subarachnoid block

Chloroprocaine was developed to meet the need for a short-acting spinal anaesthetic that is reliable and has a favourable safety profile to support the growing need for day-case surgery. Licensed in Europe for surgical procedures up to 40 minutes, chloroprocaine is an ester-type local anaesthetic with the shortest duration of action of all the established local anaesthetics. It has a significantly shorter duration of action than lidocaine and is significantly less toxic. Chloroprocaine has a motor block lasting for 40 minutes, a rapid onset time of 3–5 minutes (9.6 min ± 7.3 min at 40 mg dose; 7.9 min ± 6.0 min at 50 mg dose) and a time to ambulation of 90 minutes without complications, especially lacking transient neurologic symptomatology.

These data are based upon a retrospective review of 672 patients suitable for spinal anaesthesia in surgical procedures less than 60 minutes' duration using 30–40 mg chloroprocaine. The results showed good surgical anaesthesia, a fast onset time, and postoperative mobilization after 90 minutes without complications.[6]

The use of chloroprocaine in the subarachnoid space has been questioned.[7] In the early 1980s, several cases were reported of neurological deficits after inadvertent intrathecal injections intended for epidural delivery.[8] These doses were an order of magnitude higher than is currently used for intrathecal delivery.[9][10][11] It is also thought that these deficits were also related to the preservative sodium bisulfite,[12][13] although this is also controversial.[14][15]

In recent years, several studies have been published on the safe use of intrathecal chloroprocaine when appropriate dosage is used and with preservative-free preparations.[16][10]

It is currently approved for intrathecal use in the United States [17] and in Europe.[18]

Obstetrics

Amide-linked local anesthetic agents, such as lidocaine and bupivacaine, can become "trapped" in their ionized forms on the fetal side of the placenta, so their net transfer across the placenta is increased. An ester-linked local anesthetic agent, such as 2-chloroprocaine, is rapidly metabolized, and placental transfer is limited. Since the metabolism of 2-chloroprocaine by fetal plasma is slower than in maternal plasma, the potential for ion trapping exists. Fetal pH is slightly lower than maternal (7.32 to 7.38), thus most unionized drugs are "ion trapped" to a degree, even in a healthy fetus. Chloroprocaine (pKa 8.7) is the drug of choice for epidural analgesia and a decompensating fetus, because it does not participate in ion trapping. Placental transfer of 2-chloroprocaine is not influenced by fetal acidosis.[19]

The in vitro half-life of chloroprocaine is 21 seconds for maternal and 43 seconds for fetal blood. In patients who are homozygous atypical for plasma cholinesterase, chloroprocaine typically exists for two minutes in circulation.[20][21]

Synthesis

Chloroprocaine synthesis: H.C. Marks, H.I. Rubin, U.S. Patent 2,460,139 (1949 to Wallace & Tiernan Inc).

The hydrochloride salt of 4-amino-2-chlorobenzoyl chloride is made by the reaction of 2-chloro-4-aminobenzoic acid with thionyl chloride.[22] Synthesis of this drug is then accomplished by directly reacting the product of the last step with the hydrochloride salt of 2-diethylaminoethanol.

References

  1. ↑ "Nesacaine- chloroprocaine hydrochloride injection, solution Nesacaine MPF- chloroprocaine hydrochloride injection, solution". 1 September 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a844e68a-1462-40e4-be5e-f56214906eb9. 
  2. ↑ 2.0 2.1 "Iheezo- chloroprocaine hydrochloride ophthalmic gel gel". 27 September 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ea3b2d2c-8b33-d199-e053-2995a90a699c. 
  3. ↑ "Chloroprocaine". Drug Bank. http://www.drugbank.ca/drugs/DB01161. 
  4. ↑ Sintetica Limited (9 March 2017). "Ampres 10 mg/ml solution for injection". EMC. https://www.medicines.org.uk/emc/product/8805. 
  5. ↑ 5.0 5.1 5.2 Physicians' Desk Reference. "chloroprocaine hydrochloride". USA: PDR.net. https://m.pdr.net/Mobile/Pages/drug-summary/Nesacaine-chloroprocaine-hydrochloride-2745. 
  6. ↑ "Ampres (chloroprocaine) Summary of Product Characteristics". Perimed 3 (2): 31–34. 2009. "Cloroprocaina in chirurgia ambulatoriale: uno studio osservazionale". 
  7. ↑ "Chloroprocaine spinal anesthesia: back to the future?". Anesthesia & Analgesia 100 (2): 549–52. February 2005. doi:10.1213/01.ANE.0000143382.89888.C3. PMID 15673892. 
  8. ↑ "Persistent neurologic deficit and adhesive arachnoiditis following intrathecal 2-chloroprocaine injection". Anesthesia and Analgesia 59 (6): 452–4. June 1980. doi:10.1213/00000539-198006000-00014. PMID 7189987. 
  9. ↑ "Chloroprocaine vs. articaine as spinal anaesthetics for day-case knee arthroscopy". Acta Anaesthesiologica Scandinavica 55 (3): 273–81. March 2011. doi:10.1111/j.1399-6576.2010.02325.x. PMID 21039353. 
  10. ↑ 10.0 10.1 "Chloroprocaine 40 mg produces shorter spinal block than articaine 40 mg in day-case knee arthroscopy patients". Acta Anaesthesiologica Scandinavica 57 (7): 911–9. August 2013. doi:10.1111/aas.12107. PMID 23521140. 
  11. ↑ "Comparison of bupivacaine and 2-chloroprocaine for spinal anesthesia for outpatient surgery: a double-blind randomized trial". Canadian Journal of Anaesthesia 58 (4): 384–91. April 2011. doi:10.1007/s12630-010-9450-x. PMID 21203878. 
  12. ↑ "The chloroprocaine controversy: II. Is chloroprocaine neurotoxic?". Regional Anesthesia and Pain Medicine 9 (3): 135–45. July 1984. doi:10.1136/rapm-00115550-198409030-00004. https://rapm.bmj.com/content/9/3/135. 
  13. ↑ "Lumbar subarachnoid ethylenediaminetetraacetate induces hindlimb tetanic contractions in rats: prevention by CaCl2 pretreatment; observation of spinal nerve root degeneration". Anesthesia and Analgesia 75 (6): 895–9. December 1992. doi:10.1213/00000539-199212000-00006. PMID 1443708. 
  14. ↑ "Sodium bisulfite: scapegoat for chloroprocaine neurotoxicity?". Anesthesiology 100 (1): 85–91. January 2004. doi:10.1097/00000542-200401000-00016. PMID 14695728. 
  15. ↑ "Occurrence and comparison of sulfite oxidase activity in mammalian tissues". Biochemical Medicine and Metabolic Biology 43 (2): 159–62. April 1990. doi:10.1016/0885-4505(90)90021-r. PMID 2346671. 
  16. ↑ "The use of 2-chloroprocaine for spinal anaesthesia". Acta Anaesthesiologica Scandinavica 57 (5): 545–52. May 2013. doi:10.1111/aas.12071. PMID 23320599. 
  17. ↑ "Clorotekal: Chloroprocaine Hydrochloride". Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&applno=208791. 
  18. ↑ "Rediscovered Local Holds Promise for Spinal Anesthesia". Anesthesiology News. McMahon Publishing. 5 June 2013. http://www.anesthesiologynews.com/ViewArticle.aspx?d=Clinical+Anesthesiology&d_id=1&i=June+2013&i_id=962&a_id=23319. 
  19. ↑ "Fetal acidosis, 2-chloroprocaine, and epidural anesthesia for cesarean section". American Journal of Obstetrics and Gynecology 151 (3): 322–4. February 1985. doi:10.1016/0002-9378(85)90295-9. PMID 3970100. 
  20. ↑ Obstetric Anesthesia: Principles and Practice (3rd ed.). Philadelphia: Elsevier Mosby. 2004. p. 333. ISBN 978-0-323-02357-3. 
  21. ↑ Shnider and Levinson's Anesthesia for Obstetrics (4th ed.). Philadelphia: Lippincott Williams & Wilkins. 2002. p. 75. ISBN 978-0-683-30665-1. 
  22. ↑ "Local anesthetics" (in en). Synthesis of Essential Drugs. Amsterdam: Elsevier. January 2006. pp. 9–18. doi:10.1016/b978-044452166-8/50002-9. ISBN 978-0-444-52166-8. 

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