Abstract

Drugs called local anaesthetics are frequently utilised in clinical anaesthesia. For this class of medications to be used safely and to its full potential, understanding its pharmacology is essential. There are two sections in this chapter. The pharmacokinetics, pharmacodynamics, and chemical and physical characteristics of local anaesthetics will all be covered in the first section. Examples of regularly used doses and additives for various peripheral and regional anaesthetics will be discussed in the second section. We'll also talk about how to handle toxicity brought on by accidentally injecting local anaesthetics into the bloodstream.

Introduction

Drugs called local anaesthetics to stop electrical impulses from travelling through excitable tissues. Myocytes and nerve cells are among these tissues (both cardiac and skeletal muscles). Electrical impulse blockade is the cause of analgesia and anaesthesia. Lidocaine and other topical anaesthetics have Class I antiarrhythmic effects. An overview of the nerve anatomy is covered briefly before going into detail about the physical-chemical characteristics and mechanism of action of this class of medications. This will contribute to a better understanding of how these drugs operate as a whole and how using the right dosage and adjuncts can increase their efficacy and safety.

Nerve Anatomy

The main cells of the nervous system are neurons. The central and peripheral nerve systems make up the nervous system. Additionally, the sympathetic and parasympathetic nervous systems can be used to analyze it.

Electrical Nerve Conduction Electrophysiology

A nerve cell's resting membrane potential lies between 60 and 70 mV. Due to the presence of potassium leak channels, neurons are more permeable to potassium ions when at rest. This explains why the potassium equilibrium potential of 80 mV is closer to the resting neuronal membrane potential. The energy required for the spread of action potentials on the cell surface is provided by the ionic disequilibria. In comparison to the extracellular environment, the nerve cell's intracellular milieu is negatively charged. When nerve fibres are stimulated, changes in the nearby membrane that alternate from negative to positive values of roughly +50 mV as a result of a quick influx of sodium ions cause the electrical impulse to travel through the axon. Rapid potassium ion outflow occurs at an electrical voltage of +50 mV in an effort to keep the cell's electrical neutrality. The sodium/potassium ATPase pumps potassium ions intracellularly, whilst sodium is pumped extracellularly to restore the resting membrane potential. On the surface of the cell membrane, there are tiny, localised spikes of depolarization that represent the conduction of impulses along nerve fibres.

Specialized Local Anesthetics

In clinical settings, cocaine was first used in 1884. It was initially employed in dental surgery, then in eye surgery. At the moment, it is primarily applied topically in ENT procedures at a dosage of 4–10%. The activity begins quickly and lasts for 20 to 30 minutes. It is generally contraindicated in people with known cases of hypertension and ischemic heart disease due to its capacity to sensitise adrenergic receptors. Cocaine is a strong vasoconstrictor, thus taking it at the same time as adrenaline is not advised.

The first local anaesthetic to be developed was lidocaine in 1948. Given that it can be administered intravenously, intrathecally, and as a local infiltration, it continues to be one of the most frequently utilised anaesthetics. It is also an antiarrhythmic medication of Class 1b. Its pKa of 7.8, which is closer to the physiological pH of 7.4, and its modest water and lipid solubility give it a quick start to action. Its comparatively modest protein binding capacity of 64% and moderate duration of action make it the least hazardous of all amides. Adrenaline, a vasoconstrictor, decreases the toxicity of the substance, enabling bigger doses to be employed for local tissue infiltrations. 

Comparing mepivacaine to lidocaine and bupivacaine, its duration of action is intermediate. It first appeared in 1957. Its pKa value is 7.6. With the exception of certain worries that it might be neurotoxic in the neonate, it shares much of the same pharmacokinetic and dynamic characteristics as lidocaine. Mepivacaine is appealing for treatments like shoulder surgery due to its characteristics of low rates of systemic toxicity, fast onset, and dense motor block.

In 1976, ropivacaine was first introduced. Its pKa value is 8.2. Its chemical composition is comparable to that of bupivacaine and mepivacaine. There is just one levorotatory stereoisomer of ropivacaine available. Compared to racemic mixes of other local anaesthetics, it is a pure enantiomer and less cardiotoxic.

Both the Levo and Dextro enantiomers of buprenorphine exist. Levobupivacaine was first made available in 1995, whereas its racemic version was first released in 1963. It binds to proteins 96% of the time and has a pKa of 8.1. Bupivacaine is the longest-acting and most cardiotoxic local anaesthetic if accidentally supplied intravenously due to the increased degree of protein binding. Since its debut, it has been used successfully and has grown to be the standard by which all other long-acting local anaesthetics are measured. It's interesting to note that bupivacaine tends to cause sensory blocks at low concentrations while only somewhat sparing the motor blocks (differential sensitivity).

Conclusion

Local anaesthetics increase the toolkit that anesthesiologists have at their disposal. The safety with which these medications can be used rises with an understanding of their pharmacology. To prevent cardiorespiratory and central nervous system collapse, early toxicity detection is essential.