Question

What type of receptors or fibers can be blocked by local anesthetics? Explain in your own words and give examples.

Answer 1

An anesthetic is a drug used to induce anesthesia ⁠which result in a temporary loss of sensation or awareness.

Types:

1. General anesthetics: their action result in a reversible loss of consciousness .

2. local anesthetics: they a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

Action

In general the anaesthetics inhibit or block excitatory ligand-gated ion channels and enhance the sensitivity of inhibitory ion channels such as γ-aminobutyric acid A (GABA_A) receptor. The local anaesthetic works by moving to the inside of the cell then binding to the 'sodium channel' and thus blocking the influx of sodium ions. This block stops nerve conduction and prevents further signals reaching the brain.

Local anesthetics produce anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. eg- Local anesthetics, like Novocain, block nerve transmission to pain centers in the central nervous system by binding to and inhibiting the function of an ion channel in the cell membrane of nerve cells called the sodium channel.They are structurally related to ether, the original anesthetic.Most local anaesthetics are weak bases, having a pKa between 8 and 9, so that they are mainly but not completely ionised at physiological pH. The un-charged species penetrates the nerve sheath and axonal membrane and is then converted to the BH+ active form, which then blocks the Na+ channels.

Two basic classes of local anesthetics are the amino amides and the amino esters. Amino amides have an amide link between the intermediate chain and the aromatic end, whereas amino esters have an ester link between the intermediate chain and the aromatic end .The longer the intermediate chain, the more potent the local anaesthetic. eg: Bupivacaine has a longer intermediate chain compared to lidocaine. Bupivacaine is three to four times more potent than lidocaine.Commonly used amino amides are lidocaine, mepivacaine, prilocaine, bupivacaine, etidocaine, and ropivacaine and levobupivacaine. Commonly used amino esters are cocaine, procaine, tetracaine, chloroprocaine, and benzocaine.

The fibers blocked by local anaesthesia:

Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated fibers, and group C are unmyelinated. These groups include both sensory fibers and motor fibers.

B fibers are the most sensitive to local anasthetics. Dilation of cutaneous blood vessels is often the first sign of local anesthetic onset. C fibers and A-δ are next in sensitivity to them. They result in the inability to feel cool sensations such as an alcohol wipe.The impulses in small myelinated axons are more susceptible to lidocaine block than those in large myelinated axons. .Sensory nerves are inhibited first because they are small and do not have layers of myelin to interfere with absorption of the local anesthetic.

Lipid solubility appears to be the most significant property of local anesthetic molecules in determining anesthetic potency.Local anesthetic molecules which are highly lipophilic, easily penetrate nerve cell membranes and become intracellular, resulting in more blockade.

Lidocaine is now the most widely used local anesthetic, but different drugs are used for different purposes. For longer procedures, bupivacaine is more suitable, but it can be more painful when first administered.