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In This Article
 »  Abstract
 »  Introduction
 »  Case Report
 »  Discussion
 »  References

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 Table of Contents    
Year : 2011  |  Volume : 43  |  Issue : 2  |  Page : 214-215

Chronic phenytoin therapy-induced vecuronium resistance

1 Department of Pharmacology, Institute of Postgraduate Medical Education & Research, Kolkata, India
2 Department of Anesthesiology, R.G. Kar Medical College & Hospital, Kolkata, India
3 Department of Surgery, R.G. Kar Medical College & Hospital, Kolkata, India

Date of Submission03-Jun-2010
Date of Decision23-Oct-2010
Date of Acceptance30-Dec-2010
Date of Web Publication6-Mar-2011

Correspondence Address:
Lopamudra Chowdhury
Department of Pharmacology, Institute of Postgraduate Medical Education & Research, Kolkata
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0253-7613.77378

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 » Abstract 

This case report highlights a clinically significant pharmacokinetic drug interaction between phenytoin, a widely used anticonvulsant and vecuronium, a non-depolarizing neuromuscular blocker which led to vecuronium resistance.

Keywords: Drug interaction, phenytoin, resistance, vecuronium

How to cite this article:
Chowdhury L, Laha A, Chaudhuri T, Chatterjee S. Chronic phenytoin therapy-induced vecuronium resistance. Indian J Pharmacol 2011;43:214-5

How to cite this URL:
Chowdhury L, Laha A, Chaudhuri T, Chatterjee S. Chronic phenytoin therapy-induced vecuronium resistance. Indian J Pharmacol [serial online] 2011 [cited 2023 May 28];43:214-5. Available from: https://www.ijp-online.com/text.asp?2011/43/2/214/77378

 » Introduction Top

Vecuronium is an aminosteroid non-depolarizing type of muscle relaxant of moderate duration with minimal effect on cardiac muscarinic receptors or autonomic ganglia and does not cause histamine release. [1],[2] It is a commonly used muscle relaxant in laparoscopic operations of moderate duration. Phenytoin is one of the most commonly used anticonvulsant drugs. It induces hepatic microsomal enzymes mainly CYP3A4 and therefore has a high drug interaction potential.

 » Case Report Top

A 55-year-old female patient of neurocysticercosis, on phenytoin therapy for 3 years (plasma concentration of drug 10 μg/L), with otherwise normal clinical profile underwent laparoscopic cholecystectomy for cholelithiasis. General anesthesia (GA) was administered following routine pre-anesthetic medications comprising of inj. glycopyrrolate 0.2 mg, inj. ondansetron 4 mg, and inj. fentanyl 100 μg. Induction was done with 2.5% thiopentone sodium 250 mg and intubation with inj. succinylcholine 100 mg. GA was maintained with O 2 , N 2 O, 0.5% isoflurane and inj. vecuronium 0.1 mg. Vital parameters were monitored including blood pressure, heart rate and SPO 2 by pulse oximetry till the end of surgery. The duration of action of vecuronium was markedly reduced to 5--6 min, resulting in recurrent acquisition of lighter plane of anesthesia, bronchospasm with rapid fall in SPO 2 from 100% to 85%. Bronchospasm could not be adequately managed with standard bronchiodilators. Vecuronium drip was started at the rate of 2 μg/kg/min but hypoxia still could not be managed. Pneumoperitonium and reverse trendelenberg position of laparoscopic surgery could not be allowed and the procedure had to be converted to an open cholecystectomy. Thereafter, SPO 2 was maintained within acceptable limits but resistance to vecuronium continued till the end of surgery.

 » Discussion Top

Chronic phenytoin is reported to induce hepatic microsomal and non-microsomal enzymes, thereby leading to various drug interactions. Previously published reports have shown clinically significant drug interaction between phenytoin and various non-depolarizing neuromuscular blockers (NDNMB) mainly vecuronium, pancuronium, pipecuronium, and less commonly with atracurium. [3],[4],[5],[6],[7],[8] Long-term therapy with phenytoin or carbamazepine which are potent hepatic microsomal enzyme inducers possibly cause enhanced hepatic metabolism and inactivation of the NDNMB resulting in shortened duration of neuromuscular blockade. [3],[4],[5],[6],[7] In addition, some published reports suggest that there might be a pharmacodynamic interaction between phenytoin and vecuronium. Postulations that chronic phenytoin or carbamazepine therapy may induce a "denervation syndrome" which leads to upregulation of acetylcholine receptors leading to an increased requirement of vecuronium and thereby conferring resistance to its neuromuscular blocking action. [5] This case report is an example of an important pharmacokinetic drug interaction between phenytoin and vecuronium which occurred in a case of cholecystectomy. Chronic administration of phenytoin or carbamazepine may lead to vecuronium resistance which might be clinically significant.

 » References Top

1.McNamara JO. Pharmacotherapy of the epilepsies. In: Laurence LB, John SL, Parker LK editors. Goodman and Gilman's The Pharmacological Basis of Therapeutics.11 th ed. New York: McGraw-Hill; 2006; p.508-10.  Back to cited text no. 1
2.Porter RJ, Meldrum SB.Antiseizure Drugs. In: Katzung BG, editor. Basic and Clinical Pharmacology 11 th ed. New Delhi: Tata McGraw Hill Education Private Limited; 2009. p. 403-5.  Back to cited text no. 2
3.Wright PM, McCarthy G, Szenohradszky J, Sharma ML, Caldwell JE. Influence of chronic phenytoin administration on the pharmacokinetics and pharmacodynamics of vecuronium. Anesthesiology 2004;100:626-33.  Back to cited text no. 3
4.Ornstein E, Malteo RS, Schwartz AE, Silverberg PA, Young WL, Diaz J. The effect of Phenytoin on the magnitude and duration of neuromuscular block following Atracurium or Vecuronium. Anaesthesiology 1987;67:191-6.  Back to cited text no. 4
5.Soranio SG, Sullivan LJ, Venkatakrishnan K, Greenblatt DJ, Martyn JA Pharmacokinetics and pharmacodynamics of vecuronium in children receiving phenytoin or carbamazepine for chronic anticonvulsant therapy. Br J Anaesth 2001;86:223-9.  Back to cited text no. 5
6.Platt PR, Thackray NM. Phenytoin induced resistance to vecuronium. Anaesth Intensive Care 1993;21:185-91.  Back to cited text no. 6
7.Szenohradszky J, Caldwell JE, Sharma ML, Gruenke LD, Miller RD. Interaction of rocuronium (ORG 9426) and phenytoin in a patient undergoing cadaver renal transplantation: A possible pharmacokinetic mechanism? Anesthesiology 1994;80:1167-70.  Back to cited text no. 7
8.Palsalos PN, Perucca E. Clinically important drug interactions in epilepsy: Interactions between antiepileptic drugs and other drugs. Lancet Neurol 2003;2:473-81.  Back to cited text no. 8


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