Local Anesthetic A local anesthetic is an agent that interrupts pain impulses in a specific region of the body without a loss of patient consciousness. Normally, the process is completely reversible.

History The first local anesthetic was Cocaine which was isolated from coca leaves. It was first introduced to clinical ophthalmology as a topical ocular anesthetic.  In 1884, Dr. William Stewart Halsted was the first to describe the injection of cocaine into a sensory nerve trunk to create surgical anesthesia.

Chemistry All local anesthetics are weak bases, classified as tertiary amines. 

Esters: These include cocaine, procaine, tetracaine, and chloroprocaine. They are hydrolyzed in plasma by pseudo-cholinesterase. One of the by-products of metabolism is paraaminobenzoic acid, the common cause of allergic reactions seen with these agents

Amides: These include lidocaine, mepivicaine, prilocaine, bupivacaine, and etidocaine. They are metabolized in the liver to inactive agents. True allergic reactions are rare (especially with lidocaine)

Mechanism of Action Local anesthetics block the sodium channel They block nerve conduction by reducing the influx of sodium ions into the nerve cytoplasm. local anesthetics bind directly to the intracellular voltage-dependent sodium channels Block primarily open and inactive sodium channels, at specific sites within the channel

Factors affecting local anesthetic action 1. Effect of pH Local anesthetics are weak bases They are found mainly in 2 forms according to the PH; charged form (mainly intracellularlly, were the PH is more acidic ‘PH=6.8’) and uncharged form (mainly extracellularlly were the PH is more basic ‘PH 7.4’) Uncharged form penetrates membrane Charged form binds to receptor site Efficacy of drug can be changed by altering extracellular or intracellular pH

2. Effect of lipophilicity (ANESTHETIC POTENCY) Lipid solubility appears to be the primary determinant of intrinsic anesthetic potency. Chemical compounds which are highly lipophilic tend to penetrate the nerve membrane more easily, such that less molecules are required for conduction blockade resulting in enhanced potency. more lipophilic agents are more potent as local anesthetics

3. Effect of protein binding: increased binding increases duration of action 4. Effect of vasodilator activity : greater vasodilator activity = decreased potency and decreased duration of action

Types of nerve fibers that are susceptible to blockage by local anesthetics In general, small nerve fibers are more susceptible than large fibers

Order of sensory function block 1. pain 2. cold 3. warmth 4. touch 5. deep pressure 6. motor Recovery in reverse order

TOXICITIES OF LOCAL ANESTHETICS The result of over-dosage leading to high blood levels of the agent given. Therefore, to avoid a systemic toxic reaction to a local anesthetic, the smallest amount of the most dilute solution that effectively blocks pain should be administered.

1. Hypersensitivity. Some patients are hypersensitive (very rare cases) There are two basic types of local anesthetics (the amide type and the ester type). A patient who is allergic to one type may or may not be allergic to the other type. 2. Central Nervous System Toxicities. Local anesthetics, if absorbed systematically in excessive amounts, can cause central nervous system (CNS) excitement or can cause CNS depression.

4. Cardiovascular Toxicities. Local anesthetics if absorbed systematically in excessive amounts can cause depression of the cardiovascular system. Peripheral vascular action: arteriolar dilation (except cocaine which is vasoconstricter Hypotension.

Administraion of Local Anesthetcs 1. Infiltration Anesthesia: Local infiltration occurs when the nerve endings in the skin and subcutaneous tissues are blocked by direct contact with a local anesthetic, which is injected into the tissue. Infiltration Anesthesia is used primarily for surgical procedures involving a small area of tissue (for example, suturing a cut).

2. Topical Block. This technique is often used during examination procedures involving the respiratory tract, the eye etc For topical application, the local anesthetic is always used without epinephrine. 3. Nerve Block. In this type of anesthesia, a local anesthetic is injected around a nerve that leads to the operative site. Usually more concentrated forms of local anesthetic solutions are used for this type of anesthesia.

4. Peridural Anesthesia. This type of anesthesia is accomplished by injecting a local anesthetic into the peridural space. 5. Spinal Anesthesia. In spinal anesthesia, the local anesthetic is injected into the subarachnoid space of the spinal cord

Vasoconstrictors Vasoconstrictors decrease the rate of vascular absorption which allows more anesthetic to reach the nerve membrane and improves the depth of anesthesia. 1:200,000 epinephrine (adrenaline) appears to be the best vasoconstrictor.