K2ii / 19A01: Describe the pharmacology of lignocaine

19A01: Exam Report

Describe the pharmacology of lignocaine.

16% of candidates passed this question.

Comprehensive answers included uses (including antiarrhythmic action and a role in analgesia), physical properties and preparations, pharmacodynamics and pharmacokinetics. Its mode of action should also have been described. Many candidates focussed on toxicity and its management but provided little information on pharmacodynamics and pharmacokinetics, commonly omitting factors which affect its systemic absorption. Other common omissions were the dose required for its local anaesthetic effect and for its antiarrhythmic effect.

K2ii / 19A01: Describe the pharmacology of lignocaine

Lignocaine

Chemical

Prototype amide LA

Use

1.Reversible neuronal blockade

2.Class Ib anti-arrythmic

3.Analgesic infusion

Presentation

IV: Clear colourless soln

1-2%

+/- Adr

Also available as a spray, viscous & topical cream

Dose

1mg/kg

Epidural = 300-500mcg

Anti-arrythmic = Loading 1mg/kg IV over 2mins, then 1-4mg/min to achieve plasma levels 1-5mcg/ml

Toxic Dose

3mg/kg

7mg/kg with Adrenaline

Onset

Rapid. Often used w Adr to prolong conduction blockade and decrease systemic absorption

Route

Onset

Duration

Plain

+Adr

Topical

5min

15-30min

Infiltration

2min

75min

400min

Major N block

15-45min

60min

120min

Epidural / Caudal

15min

60min

100min

Duration

15-60mins

MoA

Unionised diffuses across neuronal cell memb

Becomes ionized within cell

Binds and OPENS Na+ ch → blocks them

↓depol of membrane → cardiac myocyte, motor & sensory n fibre Aps blocked

Cardiac myocyte: Ph 0 reduced & AP duration increases

PM cell: Ph 5 prolonged →↓automaticity

PK

A

25% UNionised at pH 7.4

Depends on site

IC > epidural > SC

Adr ↓plasma peak 30%

OBA 25% – high 1st pass

D

70% PPB a1 glycoprotein (duration)

Vd 1.5L/kg

Lipid solubility high (potency) → crosses BBB

M

N-dealkylation & hydrolysis liver.  Active metabolibtes MEGX & GX can accumulate and cause neurotoxicity

Lower seizure threshold

Lignocaine is a high extraction drug (clearance depends on HBF)

Clearance 10ml/kg/min

E

Urine excretion metabolites

10% unchanged

t1/2b 96 mins (but↑ ­ x5 in patients w hepatic dysfn)

PD

CNS

Reversible neuronal blockade

Analgesia w IV injection

CVS

↓Ph 4 rate depol

↓automaticity

RESP

bronchodilation

AE

MetHb

Narrow therapeutic window

<5mcg/ml

>5mcg/ml → CNS → confusion, agitation, paraesthesia

>20mcg/ml → H → AV block, unresponsive, hypotension, cardiac arrest