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