Question 1

 Describe the pharmacology of lignocaine.

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College Answer

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.

Discussion

Class Class Ib antiarrhythmic
Chemistry Aminoamide
Routes of administration IV, inhaled, subcutaneous
Dose

Anaesthetic (regional infiltration) maximum dose 4mg/kg, with adrenaline 8mg/kg

Infused dose for antiarrhythmic effect = 1-2mg/kg loading dose,
followed by 1-2mg/kg/hr infusion

Absorption Oral bioavailability = 35%
Solubility pKa = 7.9; about 25% is not ionised at pH 7.4
Distribution VOD= 0.9L/kg; 70% protein-bound
Target receptor Nav1.5 subunit of the fast voltage-gated sodium channels
Metabolism Hepatic metabolism (90-95%)
Elimination Minimally renally excreted; half-life 10-20 minutes following IV bolus, closer to 45-90 minutes with subcutaneous infiltration
Time course of action Duration of action is similar to half-life
Mechanism of action Regional anaesthesia, by differential block (pain and temperature finres are blocked earlist). With higher doses, also motor block. In toxicity, CNS effects (visual disturbances, perioral mumbness, delirium,seizures, coma) and cardiovascular side effects (initially tachycardia and hypertension followed by bradycardia, negative inotropy, vasodilation and arrhythmias) Does not prolong the QRS, and actually shortens the QT.
Clinical effects Antiarrhythmic effect, analgesic and local anaesthetic effects. Lowers seizure threshold, causes CNS excitation. Does not prolong the QRS, and actually shortens the QT.
Single best reference for further information Weinberg et al (2015)

References

HOLMDAHL, M. H: SON. "Xylocain (lidocaine, lignocaine), its discovery and Gordh's contribution to its clinical use." Acta Anaesthesiologica Scandinavica 42 (1998): 8-12.

Eipe, N., S. Gupta, and J. J. B. E. Penning. "Intravenous lidocaine for acute pain: an evidence-based clinical update." Bja Education 16.9 (2016): 292-298.

Weinberg, Laurence, et al. "Pharmacokinetics and pharmacodynamics of lignocaine: A review." World Journal of Anesthesiology 4.2 (2015): 17-29.