MC Rajesh
Department of Anaesthesia, Pain and Peri-operative Medicine,
Baby Memorial Hospital, Kozhikode, Kerala, India. PIN: 673004
Address for Correspondence: Dr. MC
Rajesh MD, MBA, Senior Consultant Anaesthesiologist, Baby
Memorial Hospital, Kozhikode, Kerala, India. PIN:
673004. E- mail: rithraj2@yahoo.co.in
Keywords: Lidocaine
Introduction
Off label prescription of pharmacological agents are common in
clinical practice. Subsequently some of these drugs are
recognized on a regular basis. Unanticipated pharmacological
actions are noticed either in the evolution phase of drug or
following some interesting observations reported during
clinical practice. One such agent of interest to
anaesthesiologists is Lidocaine. Multiple possible therapeutic
options of this agent are now critically elucidated.
Anaesthesiologists are familiar with lidocaine's potency to
blunt airway irritability and cardiac arrhythmias.
Interestingly its roles as antitumor agent as well as possible
antibacterial and antiviral are now increasingly explored. The
following text is a brief description of lidocaine's
established and emerging roles other than of a local
anaesthetic.
As bronchodilator and antispasmodic agent
Asthma is a chronic disease of respiratory system
characterised by airway hyper responsiveness and lung
inflammation leading to airway obstruction [1]. Bronchospasm
can present as a significant life threatening perioperative
complication in asthmatic patients [2]. Pathophysiological
hallmark of the disease is eosinophil and lymphocyte
infiltration. Conventional treatment options in asthmatic
patients involve combination of bronchodilators and
glucocorticoids. But both these drugs carry plurality of side
effects. Treatment with bronchodilator alone will give the
patient a relieving sensation while masking the progressive
deterioration in the inflammatory process. It was known since
long that treatment with lidocaine intravenously or as
aerosol will prevent airway hyperactivity [3]. But in
occasional patients aerosolized lidocaine itself can
precipitate airway irritation, broncho-constriction and
even a claustrophobic sensation [4]. When Groben et al
compared the airway effects of lidocaine, dyclonine (more
powerful local anaesthetic potency) and ropivacaine, they
noted that lidocaine had a more powerful effect on attenuating
bronchospasm [5]. This reflects that it is not the local
anaesthetic potency of the molecule which is facilitating
relief from bronchospasm. At this juncture it is relevant to
recollect an interesting finding made by Ohnishi T et al
wherein it was stated that the broncho-alveolar lavage of
patients with bronchial asthma had significant suppression of
eosinophil viability [6]. The underlying mechanism is
explained due to apoptosis and not due to cytotoxicity [7].
All these finding paving the way for a potential therapeutic
use of lidocaine in bronchospasm therapy. Different
formulations of lidocaine analogues were tried which has less
of local anaesthetic property but have profound action on
airway hyperactivity. JMF2-1 is a fluorinated lidocaine
molecule with reduced anaesthetic action was one which was
extensively evaluated initially [8]. But concerns were raised
with JMF2-1 as it being a fluorinated analogue. Fluorinated
compounds are known to cause potential adverse effects such as
haemolytic anaemia and DNA damage [9]. So another analogue of
lidocaine, JM25-1 was pharmacologically evaluated. This
molecule was found to have limited impact on Na⁺channels but
more effective than the parent compound as a bronchodilator
and anti-inflammatory agent [8]. This holds promise as a
future bronchodilator and antispasmodic with fewer side
effects of beta agonists and steroids.
Antiarrythmic agent
Lidocaine has a well established role as an antiarrhythmic
agent. It is recommended as per advanced cardiac life support
guidelines (ACLS) for the treatment of acute haemodynamically
compromising ventricular arrhythmias. This can happen
following myocardial ischemia / infarction or during cardiac
manipulations (during cardiac surgery, cardiac
catheterization) [10]. At the molecular level, lidocaine acts
as a membrane stabilizing agent. It acts on the sodium channel
in the inactive state and inhibits its recovery after
repolarisation. Thus ventricular arrhythmias are controlled by
suppressing the automaticity and spontaneous depolarization of
the ventricular diastole.
Antitumor Action?
There is evidence to show that lidocaine and other local
anaesthetic drugs can potentiate chemotherapeutic agents in
vivo. Murakami et al has shown that when photofrin was
dissolved in lidocaine jelly during photodynamic therapy, the
effect was greater than direct application of photofrin alone
[11]. Lidocaine and Dibucaine are known to enhance the
cytotoxic effect of the antitumor antibiotic bleomycin [12].
Recently Lirk et al has shown that at clinically relevant
doses, Lidocaine exerts demethylating effects on breast
cancer cells [13]. Ropivacine was also shown to have the same
effects on specific cancer cell lines [13]. A decrease in
methylation can reactivate tumour suppressor genes and will
help to arrest tumour growth. Another interesting finding of
this in vitro study was the additive effect of lidocaine in
combination with chemotherapeutic agent 5-aza-2'-deoxycytidine
[13].
Antibacterial and Antiviral?
Numerous studies have shown the bacteriostatic, bactericidal,
fungistatic and fungicidal properties of local anaesthetics
against wide spectrum of microorganisms [14]. Interestingly,
local anaesthetics differ in their antimicrobial potency also.
Bupivacaine and Lidocaine has significantly more action on the
microbes compared to ropivacaine [14]. Zekine
Begec et al has shown that Lidocaine significantly inhibited
the growth of S. aureus, E. coli and P. aeruginosa [15]. When
mixed with Propofol, Lidocaine 2% was found to reduce not only
the pain of injection but also found to reduce the harmful
consequences of possible microorganism contamination [16].
Preservatives in Lidocaine were found to have no bacteriocidal
activity, but weak bacteriostatic action only [17]. The
perceived mechanism of local anaesthetics against
antimicrobials is believed to be by disruption of microbial
cell membrane permeability, leading to leakage of cellular
components and cell destruction [14]. More research needed to
confirm whether local anaesthetics can act as an adjunct to
traditional antimicrobials. But in view of its proven
antimicrobial actions, caution is to be exercised while
administering local anaesthetics prior to any diagnostic
procedures.
Conclusion
Lidocaine's pharmacological indications as local anaesthetic
and antiarrythmic agent are well recognized. But there is
ample evidence in current literature to support the use of
this molecule as an antitumor agent, antimicrobial, and as a
bronchodilator. There is scope for further extensive
pharmacological research before Lidocaine is used regularly
for these extended indications.
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