Describe the pharmacology of lidoocaine
71% of candidates passed this question.
The answers for this question were generally of a good standard. Lidocaine is a core drug in intensive care practice and thus a high level of detail was expected. This question was best structured using a standard pharmacology template (pharmaceutics, pharmacokinetics and pharmacodynamics). A small number of answers omitted any pharmaceutic elements. Another common error was the use of vague and imprecise statements. For example, many answers stated that the maximum dose (without adrenaline) is 3 mg/kg, without specifying that this is subcutaneous.
The concept of the ratio of the dose required to produce cardiovascular collapse to that required to induce seizures (CC/CNS ratio) was often mentioned. However, in many cases this was conveyed simply as an abbreviated statement without any additional explanation leaving the examiner unsure as to whether the candidate understood the concept (and thus unable to award any additional marks). In addition, many candidates confused the order of this ratio (incorrectly referring to it as a CNS/CC ratio of 7). Lastly, few answers made specific mention of the narrow therapeutic index and the associated implications for use in the ICU.
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
Author: Krisoula Zahariou