Level 1

amide local anaesthetic
class IB antiarrhythmic
Na channel blocker

Lip sol high – crosses BBB. pKa 7.9

tertiary amine which is an amide derivative of diethylaminacetic acid.

Local anaesthetic

6.8–11.6 ml/min/kg

↓ in the presence of cardiac and hepatic failure.

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.

Antiarrhythmic –
Vaughan Williams Class Ib
Na channel blocker

reduces nerve propagation in the PNS (and CNS) and in cardiac tissue- to treat ventricular arrhythmias. Also used to treat cerebral gas embolism (controversial)

PO: Viscous
IM/IV: 1% or 2% sol (10-20mg/ml).
Also with Adr.
Inf: SS in 7hrs

Blocks Na+ channels in cardiac muscles, motor&sensory nerve fibres
mild↓ Phase 0 slope
↓APD ↓ERP
In pacemaker cells: phase 4 prolonged → ↑ threshold potential → ↓automaticity

CVS:
↓ electrical excitability, conduction rate, force of contraction

CNS
Stimulation

narrow therapeutic window, with ideal concentrations 5 mcg/ml: CNS effects including confusion, sedation, agitation and paraesthesia.
>20 mcg/ml: AV block, unresponsive hypotension and eventually death.

SC, IV/IM, ETT
On/dur: 45-90sec / 10-20min

60-80%

1.1-2.1 L/kg (alt in CHF/CLF)

90% hepatic; active metabolites monoethylg
lycinexylidide (MEGX) and glycinexylidide (GX) can accumulate and cause CNS toxicity

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

half life Biphasic: Prolonged with CHF, Liver, shock, ARF/CRF
Initial: 7-30 minutes; Terminal: 2 hours

SC, IV/IM, ETT
IV 75-100mg -> infusion 2mg/min
Max dose: 3mg/kg or 7mg/kg with Adr

Amide Local Anaesthetic

1. as a local anaesthetic
2. in the treatment of ventricular tachydysrhythmias, acting as a class Ib
antiarrhythmic.

Solution: clear, colourless solution in concentrations of
0.5/1/1.5/2% solution of lidocaine hydrochloride (with or without
1:200 000 adrenaline)

Others:
- - Gel: 21.4 mg/ml of lidocaine hydrochloride (with or without chlorhexidine gluconate)
- a 5% ointment
- 10% Spray
- 4% aqueous solution for topical application
- a cream/
suppositories (in combination with hydrocortisone) for rectal administration
- 1% and 2% preparations are available with or without the preservatives methylhydroxybenzoate (1.7 mg/ml) and propylhydroxybenzoate
(0.3 mg/ml). Hydrochloric acid and sodium hydroxide are also present in
some formulations (the latter to a maximum of 1%).

The pKa of lidocaine
is 7.7 and is 25% unionized at a pH of 7.4. The heptane:buffer partition
coefficient is 2.9.

Local anaesthetics diffuse in their uncharged base form
through neural sheaths and the axonal membrane to the internal surface
of cell membrane Na+ channels; here they combine with hydrogen ions
to form a cationic species which enters the internal opening of the Na+
channel and combines with a receptor. This produces blockade of the Na+
channel, thereby decreasing Na+ conductance and preventing depolarization of the cell membrane

CVS In low concentrations, lidocaine decreases the rate of rise of phase 0
of the cardiac action potential by blockade of inactivated sodium channels.
This results in a rise in the threshold potential, with the duration of the
action potential and effective refractory period being shortened. It has few
haemodynamic effects when used in low doses, except to cause a slight
increase in the systemic vascular resistance, leading to a mild increase in the
blood pressure. In toxic concentrations, the drug decreases the peripheral
vascular resistance and myocardial contractility, producing hypotension and
possibly cardiovascular collapse.
RS The drug causes bronchodilatation at subtoxic concentrations.
Respiratory depression occurs in the toxic dose range.
CNS The principal effect of lidocaine is reversible neural blockade; this leads
to a characteristically biphasic effect in the CNs. Initially, excitation (lightheadedness, dizziness, visual and auditory disturbances, and seizure activity)
occurs due to inhibition of inhibitory interneurone pathways in the cortex.
With increasing doses, depression of both facilitatory and inhibitory pathways occurs, leading to CNs depression (drowsiness, disorientation, and
coma). Local anaesthetic agents block neuromuscular transmission when
administered intraneurally; it is thought that a complex of neurotransmitter,
receptor, and local anaesthetic is formed, which has negligible conductance.
AS Local anaesthetics depress contraction of the intact bowel.
Metabolic/other Lidocaine may have some anticholinergic and antihistaminergic activity

Lidocaine is intrinsically less toxic than bupivacaine.
Allergic reactions to the amide-type local anaesthetic agents are extremely
rare. The side effects are predominantly correlated with excessive plasma
concentrations of the drug, as described above. Methaemoglobinaemia may
occur if doses in excess of 600 mg are used and is caused by the metabolite
o-toluidine, although this condition may occur at lower doses in patients
suffering from anaemia or a haemoglobinopathy or in patients receiving
therapy known to also precipitate methaemoglobinaemia (sulfonamides).
Use of lidocaine for paracervical block or pudendal nerve block in obstetric
patients is not recommended, as this may give rise to methaemoglobinaemia in the neonate, as the erythrocytes are deficient in methaemoglobin
reductase.

The absorption of local anaesthetic agents is related to:
1. the site of injection (intercostal > caudal > epidural > brachial plexus >
subcutaneous)
2. the dose—a linear relationship exists between the total dose and the
peak blood concentrations achieved, and
3. the presence of vasoconstrictors which delay absorption.

64–70%
predominantly to alpha-1 acid glycoprotein

0.7–1.5 l/kg.

Lidocaine is metabolized in the liver by N-dealkylation, with
subsequent hydrolysis to monoethylglycine and xylidide. Monoethylglycine
is further hydrolysed, whilst xylidide undergoes hydroxylation to 4-hydroxy-
2,6-xylidine which is the main metabolite and excreted in the urine.
Metabolites of lidocaine may lower the fit threshold, thereby potentiating
seizure activity, whilst others have some antiarrhythmic properties.

Less than 10% of the dose is excreted unchanged in the urine.

elimination half-life is 90–
110 minutes.

Lidocaine may be administered topically, by infiltration, intrathecally, or epidurally;

the toxic dose of lidocaine is 3 mg/kg (7 mg/kg with adrenaline).
The maximum dose is 300 mg (500 mg with adrenaline).

The adult intravenous dose for the treatment
of acute ventricular dysrhythmias is a bolus injection of 1 mg/kg, administered over 2 minutes. A second dose may be administered according to the response of the patient. This is normally followed by an infusion at a rate
of 20–50 micrograms/kg/min. Lidocaine acts in 2–20 minutes (dependent
on the rate of administration and the presence of vasoconstrictors and the
concentrations used).

The speed of onset of lidocaine may be increased
by the addition of bicarbonate to increase the pH of the solution, thereby
increasing the unionized fraction of drug. The pH of the drug is approximately 6.4.