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