Editorial :
Kentaro Ouchi
Dental local anesthetics contain vasoconstrictors,
such as adrenaline and felypressin, to enhance the anesthetic effects and
reduce bleeding in the surgical field. Adrenaline has been
used for long periods of time as an additive to local anesthetics. With a
typical dose range of 10 - 12.5 μg /mL, adrenaline is believed to prolong
duration by its vasoconstrictive properties that prevent systemic reabsorption
of local anesthetics. Several reports have warned against the use of dental local anesthetics
containing adrenaline in patients with cardiovascular diseases [1, 2] On other hand, felypressin, a
non-catecholamine vasopressor
that is chemically related to vasopressin, has been used as a safe
vasoconstrictor in patients with compromised cardiovascular status in Japan and
European Union nations [3]. However, there have been reports that, in a dog
study, clinical doses of felypressin caused decreases in coronary blood flow
[4]. But, in ferypressin
contained propitocaine,
ferypressin have maintained oxygen supply in myocardial tissues by
maintained myocardial blood flow [5]. An α-2 adrenoceptor agonist,
clonidine, combined with a local anesthetic, has been found to extend the
duration of the peripheral nerve block. The action of clonidine was suggested
to be due to local vasoconstriction [6].
But, clonidine is not particularly specific for α-2 adrenoceptors and acts
via α-1 adrenoceptors at comparatively high concentrations. Thus, it is unclear
whether it acts via α-2 adrenoceptors. And despite substantial study, it is not
clear which doses of clonidine are optimal for prolongation of analgesia after
peripheral nerve blocks. The use of perineural clonidine is not currently
recommended for clinical use [7]. On the other hand, another α-2
adrenoceptor agonist, dexmedetomidine,
acts more specifically against α-2 adrenoceptors and has more than 7-8 times
the affinity for α-2 adrenoceptors of clonidine. Dexmedetomidine, which produce
sympatholytic, sedative, analgesic, antihypertensive and bradycardiac effects
when combined with a local anesthetic agent, have been found to extend the
duration of local anesthesia effect by causing local vasoconstriction.
Dexmedetomidine is a selective α-2 adrenoceptor agonist. α-2 adrenoceptors are
subdivided into four subtypes: α-2A, α-2B, α-2C and α-2D. The α-2A, α-2B and
α-2C adrenoceptors
have been well identified pharmacologically and have been shown to cause
vasoconstriction [8-10]. The other possible mechanism for enhancement and
prolongation of local anesthetic action by dexmedetomidine is its direct effect
on peripheral nerve activity. A direct action of dexmedetomidine has been
reported on exposure of isolated sciatic nerve fibers to dexmedetomidine [11].
However, direct effect of dexmedetomidine on peripheral nerve activity was not
observed in-vivo [12]. It is reported that dexmedetomidine administered alone
for epidural anesthesia,
at the concentration that was shown in this study to effectively enhance local
anesthetic action, produced no local anesthesia effects [12]. A possible
explanation for this discrepancy is that epidural anesthesia involves injection
of the local anesthetic solution into the epidural space, which includes loose
connective tissue. The pterygomandibular
space, which is the region where the drug is injected for Inferior Alveolar
Nerve Block, also includes loose connective tissue, making it similar to the
epidural space. In conduction anesthesia involving penetration of a nerve fiber
in connective tissue and jawbone, dexmedetomidine enhances the local anesthetic
action of lidocaine by vasoconstriction via α-2A, α-2B and α-2C adrenoceptors
around the site of injection. Based on the mechanism that the local anesthesia
reinforcement action of dexmedetomidine depends on local vasoconstriction,
using a sedated tail flick and epidural animal model,
we previously reported that prolongation of the local anesthetic effect
by dexmedetomidine was concentration-dependent [12,13]. We studied dexmedetomidine for local
anesthetic, now. Use of a new drug, dexmedetomidine, that can replace adrenaline and
felypressin for the safe enhancement of local anesthesia effect in patients
with cardiovascular diseases, may be recommended. 1. Meechan JG, Parry G, Rattray
DT, Thomason JM. Effects of dental local anaesthetics in cardiac transplant
recipients (2002) Br Dent J. 192:161-163. 2. Sims PG, Kates CH, Moyer DJ,
Rollert MK, Todd DW. Anesthesia in outpatient facilities (2012) J Oral
Maxillofac Surg 70:e31-49. 3. Inagawa M, Ichinohe T, Kaneko
Y. Felypressin, but not epinephrine, reduces myocardial oxygen tension after an
injection of dental local anesthetic solution at routine doses (2010) J Oral
Maxillofac Surg. 68:1013-1017. 4. Agata H, Ichinohe T, Kaneko Y.
Felypressin-induced reduction in coronary blood flow and myocardial tissue
oxygen tension during anesthesia in dogs (1999) Can J Anaesth. 46:1070-1075. 5. Ouchi K, Sunada K. Effect of
propitocaine with felypressin on myocardial blood flow and cardiac output in
spontaneous hypertensive rats (2008) Anesth Prog. 55:59-61. 6. Yoshitomi T, Kohjitani A,
Maeda S, Higuchi H, Shimada M, et al. Dexmedetomidine enhances the local
anesthetic action of lidocaine via an alpha-2A adrenoceptor (2008) Anesth Analg. 107:96-101. 7. Kirksey MA, Haskins SC, Cheng J, Liu SS.
Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of
Analgesia: A Systematic Qualitative Review (2015) PLoS One 10:e0137312. 8. Duka I, Gavras I, Johns C, Handy DE, Gavras
H. Role of the postsynaptic alpha (2)-adrenergic receptor subtypes in
catecholamine-induced vasoconstriction (2000) Gen Pharmacol. 34:101-106. 9. Snapir A, Koskenvuo J, Toikka J,
Orho-Melander M, Hinkka S, et al. Effects of common polymorphisms in the
alpha1A-, alpha2B-, beta1- and beta2adrenoreceptors on haemodynamic responses
to adrenaline (2003) Clin Sci 104:509-520. 10. Chotani MA, Mitra S, Su BY,
Flavahan S, Eid AH, et al. Regulation of alpha(2)-adrenoceptors in human
vascular smooth muscle cells (2004) Am J Physiol Heart Circ Physiol.
286:H59-67. 11. Kosugi T, Mizuta K, Fujita T, Nakashima M,
Kumamoto E. High concentrations of dexmedetomidine inhibit compound action
potentials in frog sciatic nerves without alpha(2) adrenoceptor activation
(2010) Br J Pharmacol. 160:16621676. 12. Ouchi K, Koga Y, Nakao S,
Sugiyama K. Dexmedetomidine dosedependently enhances local anesthetic action of
lidocaine (2014) J Oral Maxillofac Surg. 72 : 474-480. 13. Ouchi K, Sekine J, Koga Y,
Nakao S, Sugiyama K. Establishment of an animal model of sedation using
epidural anesthesia that uses the tail-flick test for evaluating local
anesthetic effects in rats (2013) Exp Anim. 62 : 137-144. Vasoconsstrictors,local anesthetics, Adrenaline, Vasopressors
Vasoconstrictor for Local Anesthetics
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