Mechanism

Controversies

Sistemic Toxicity

Bagianto

Medical Faculty

Brawijaya University

Local anesthetics (LA) widely usedhave similar chemical structuresdiffering pharmacokinetic properties and

spectra of pharmacodynamic effects although it is rare for patients to manifest

serious adverse effects or experience complications secondary to LA administration adverse events do occur !!

(Shipton, 2012)

MECHANISMSMECHANISMS

Mechanisms of Action of LADirectly block transmission of pain from

nociceptive afferentsefficacy the inward Na+ current is blocked at the

sodium ionophore during depolariationAlso block

Ca2+ and K+ channels, transient receptor potential vanniloid-1 receptors, and other ligand-gated receptors.

also disrupt the coupling between certain G proteins and their associated receptors.

Hantaran Impuls Sensorik

Block Na+ channels with loss of nerve conduction

Therefore we call the result of LA action…

Conduction Block

Mechanisms of action

Ionized/Non-ionized Pairs

The Na+ Channel- Site of LA Action

Secara reversibel menghambat transmisi sinyal dari serabut saraf dengan cara menghambat masuknya ion natrium kedalam sel membran dari serabut saraf.

10Naropin Indonesia PI

Mechanisms of action

LA exert potent anti-inflammatory effects, on neutrophil priming reactions

LA inhibit local inflammatory response to injury sensitise nociceptive receptors contribute to pain and hyperalgesia

Studies have observed that LA :reduce the release of inflammatory mediators from

neutrophils, reduce neutrophil adhesion to the endothelium, reduce formation of free oxygen radicals, and decrease oedema formation

Mechanisms of Action of LA

intravenous LA antithrombotic and neuroprotective actions independent of Na+ channel blockade

LA alleviate some types of neuropathic pain, related to sensitization of the antinociceptive pain pathways that occur in the neuropathic pain state;

spinal glial cells play some part in this as well

(Shipton, 2012)

Mechanisms of Action of LA

CONTROVERSIESCONTROVERSIES

Nanotechnology

With nanotechnology, an antidote to bupivacaine overdose is possible

There is a formation of pi–pi complexes between bupivacaine and a pi-electron–rich injectable nanoparticle

This complex would be devoid of the clinical effects of bupivacaine and render toxic bupivacaine harmless

(Agarwal, 2012)

Nanotechnology

Nanotechnology

Anesthesia-containing nanoparticles drawn to the targeted area of the body by magnets

useful alternative to nerve block for local anesthesia in patients

The researcher have established proof of principle that it is possible to produce ankle block in the rat by intravenous injection of magnetic nanoparticles associated with ropivacaine and magnet application at the ankle

With further study, the nano-anesthesia technique might allow more potent doses of local anesthetics to be delivered safely during local anesthesia in humans

(Venkat R. et al, 2014)

Nanotechnology

the researchers extend continuous pain relief from lidocaine for up to a

week and show that the pain relief was equal to that provided by

daily use of an opioid drug, or narcotic.In the future,

this system could help reduce postoperative pain, the most common reason for readmission after

ambulatory surgeryInnovations in pain treatment :

less reliance on narcotics, faster recovery times, and fewer hospital readmissions

(Iliades C, 2014)

Nanotechnology

Nanotechnology

LAST LAST

Local Anesthetics Sistemic ToxicityLocal Anesthetics Sistemic Toxicity

LASTthese range from mild to severe toxicitymild symptoms systemic absorption of local

anesthetic from a correctly sited and appropriately dosed regional anesthetic procedure

major symptoms central nervous system (CNS) and/or cardiac toxicity (most often from unintentional intravascular injection)

can result in disability or death !!

A variety of factors influence the likelihood and severity, including:- individual patient risk factors- concurrent medications- location and technique of block - specific local anesthetic compound - total local anesthetic dose - timeliness of detection, and - adequacy of treatment

Shipton, Edward. Review Article. New Formulations of Local Anaesthetics—Part I. Hindawi Publishing Corporation. Anesthesiology

Research and Practice. Volume 2012

LAST

New effective delivery systems modulate the release rate of these drugs, extend their anesthetic effect, and enhance their localization

New innovations LA formulations lead to prolonged action or to novel delivery approaches

New properties may still be discovered new applications of this class of drugs may still be anticipated

LAST

LAST

recent development of ultrasound guided regional anesthesia (UGRA) and lipid emulsion therapy

Considering

(1) the extensive use of local anesthetics,

(2) the frequent use of doses sufficient to cause significant morbidity or mortality, and

(3) the imperfect nature of our ability to prevent, detect, and treat these complications

LAST

LAST

The current agreed hypothesis for ILE’s

efficacy in treating cardiotoxicty, although not well defined

but supported by in vitro studies, is the formation of a “lipid sink”; that is, an expanded intravascular lipid phase that acts to absorb the offending circulating lipophilic toxin

Mechanisms of action

It remains the responsibility of all clinicians using LA

to understand their potential for severe systemic toxicity and to be prepared to

respond immediately to these events when they occur.

33

THANK YOUTHANK YOU

References Shipton, Edward. Review Article. New Formulations of Local Anaesthetics—

Part I. Hindawi Publishing Corporation. Anesthesiology Research and Practice. Volume 2012

Wildsmith, Tony. Principles and Practice of Regional Anaesthesia 4th ed. History and development of local anaesthesia. Oxford University Press. Published online: Nov 2012

Malamed, Stanley. What's New in Local Anesthesia? School of Dentistry, University of Southern California. Anesth Prog 39:125-131 1992

Neal, Joseph et al. ASRA Practice Advisory on Local Anesthetic Systemic Toxicity. Regional Anesthesia and Pain Medicine & Volume 35, Number 2, March-April 2010

Agarwal A. The future of anaesthesiology. Indian J Anaesth. 2012 Nov-Dec; 56(6): 524–528.

Venkat R. R. Mantha, Harsha K. nair, Raman Venkataramanan, Yuan Yue Gao, Krzysztof Matyjaszewski, Hongchen Dong, Wenwen Li, Doug Landsittel, Elan Cohen, William R. Lariviere. Nanoanesthesia. Anesthesia & Analgesia, 2014; 1

Iliades C. Pain Management. Nanoparticles: The High-Tech Way to Treat Pain. http://www.everydayhealth.com/pain-management/nanoparticles-the-high-tech-way-to-treat-pain.aspx viewed Sept 5th, 2014