Role of Calcium in Local Anaesthesia

Local anaesthetics (LAs) block nerve conduction of sensory impulses (mainly pain, temperature, touch and deep pressure). The most commonly used ones are Lidocaine, Bupivacaine, Tetracaine, Procaine and Ropivacaine. At physiologic pH, they are cationic and interacts with the protein receptor of the voltage gated Na+ channel to inhibit its function and achieve local anaesthesia. Moreover, exposure to higher concentration of Ca2+ reduces inactivation of Na+ channels and lessens the degree of block. The bound Ca2+within the cell membrane are presumed to exert a regulatory role on the movement of Na+across the nerve membrane. The proposed mechanism includes: The displacement of the Ca2+from the sodium receptor site, which allows the binding of local anaesthetics, blockade of sodium channels, decrease in sodium conductance, and decrease in rate of depolarisation and finally conduction blockade. The aforementioned process includes the rise in the level of intracellular Calcium levels from the Endoplasmic reticulum. LAs indirectly inhibit the Calcium channels, thereby decreasing its influx.  These released Ca2+ intracellular and the non-entered extracellular ions can exert various actions. The local anaesthetics form a more stable bond at the site from where calcium ions are displaced and exert their local anaesthetic action.

For example : In the myocardium, There is LA mediated slow release of Calcium from the sarcoplasmic reticulum, with an increased reduction in the amount of calcium required for myocardial contractility. The decreased entry and reduced intracellular calcium storage results in decreased myocardial contractility.

Prepared by:

Janice Jacson M
Pharm D
Nirmala College of Pharmacy,
Muvathupuzha,
Kerala.