Core pharmacology

Introduction

amide local anaesthetic
class IB antiarrhythmic
Na channel blocker

Distribution

Lip sol high – crosses BBB. pKa 7.9

Chemical Pharmaceutics

tertiary amine which is an amide derivative of diethylaminacetic acid.

Main Action

Local anaesthetic

Clearance

6.8–11.6 ml/min/kg

↓ in the presence of cardiac and hepatic failure.

Special Points

The onset and duration of conduction blockade are
related to the pKa, lipid solubility, and the extent of protein binding. A low
pKa and high lipid solubility are associated with a rapid onset time; a high
degree of protein binding is associated with a long duration of action. Local
anaesthetic agents significantly increase the duration of action of both
depolarizing and non-depolarizing relaxants.
Due to the narrow therapeutic index of lidocaine, the plasma concentrations of the drug need to be monitored in patients with cardiac and hepatic
impairment.
Lidocaine is not removed by haemodialysis.
Intravenous administration of lidocaine decreases N
2o and halothane
requirements by 10% and 28%, respectively.
EMLA® (Eutectic Mixture of Local Anaesthetics) is a white cream used to
provide topical anaesthesia prior to venepuncture and has also been used
to provide anaesthesia for split skin grafting. It contains 2.5% prilocaine and
2.5% lidocaine in an oil–water emulsion. When applied topically under an
occlusive dressing, local anaesthesia is achieved after 1–2 hours and lasts for
up to 5 hours. The preparation causes temporary blanching and oedema of
the skin; detectable methaemoglobinaemia may also occur in the presence
of excessive o-toluidine plasma levels as a metabolite of prilocaine.

Indications Uses

Local anaesthesia and treatment of ventricular tachydysrhythmias as a class Ib antiarrhythmic.

Presentation

Clear, colourless lidocaine hydrochloride solutions in 0.5%, 1%, 1.5% and 2% concentrations, with or without adrenaline. Topical gel, ointment, spray and other formulations are also available.

Mechanism of action

Blocks voltage-gated sodium channels. In nerves this prevents depolarisation and impulse conduction. In cardiac tissue it preferentially blocks inactivated sodium channels, reducing phase-0 upstroke and shortening action-potential duration and effective refractory period.

Physiological effects

At low concentrations lidocaine reduces cardiac phase-0 upstroke and shortens action-potential duration and effective refractory period. At toxic concentrations it reduces myocardial contractility and may cause hypotension. CNS effects are biphasic, with excitation and seizures followed by depression at higher concentrations.

Absorption

Systemic absorption after local administration varies with injection site, total dose and the presence of a vasoconstrictor, which delays absorption.

Protein binding

64-70% protein-bound in plasma, predominantly to alpha-1 acid glycoprotein.

Volume of distribution

Volume of distribution approximately 0.7-1.5 L/kg.

Metabolism

Hepatic N-dealkylation with subsequent metabolism to monoethylglycine and xylidide derivatives. Several metabolites retain biological activity.

Excretion

Urine (<10% unchanged , ~90% metabolites)

Half-life

Elimination half-life approximately 90-110 minutes.

Route And Dose

May be administered topically, by infiltration, intrathecally or epidurally. For ventricular tachydysrhythmias the referenced text gives an intravenous bolus of 1 mg/kg over 2 minutes followed, when required, by an infusion of 20-50 micrograms/kg/min. Maximum local-anaesthetic dose in the referenced text is 3 mg/kg without adrenaline and 7 mg/kg with adrenaline.

Class Group

Amide local anaesthetic and Vaughan Williams class Ib sodium-channel-blocking antiarrhythmic.

Adverse Effects Toxicity

Concentration-related CNS and cardiovascular toxicity. Allergic reactions to amide local anaesthetics are rare. Methaemoglobinaemia may occur, particularly with large doses or susceptible patients.