Local Anesthetics

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--the agent does not produce any residual effect on the nerve fiber.

History The first local anesthetic was Cocaine which was isolated from coca leaves by Albert Niemann in Germany in the 1860s. The very first clinical use of Cocaine was in 1884 by Sigmund Freud who used it to wean a patient from morphine addiction.  It was Freud and his colleague Karl Kollar who first noticed its anesthetic effect.  Kollar first introduced it to clinical ophthalmology as a topical ocular anesthetic.  Also 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 work to block nerve conduction by reducing the influx of sodium ions into the nerve cytoplasm. Sodium ions cannot flow into the neuron, thus the potassium ions cannot flow out, thereby inhibiting the depolarization of the nerve.  If this process can be inhibited for just a few Nodes of Ranvier along the way, then nerve impulses generated downstream from the blocked nodes cannot propagate to the ganglion.

Mechanism of action local anesthetics bind directly to the intracellular voltage-dependent sodium channels Block primarily open and inactive sodium channels, at specific sites within the channel

Mechanism of action 1) slow rate of depolarization 2) reduce height of action potential 3) reduce rate of rise of action potential 4) slow axonal conduction 5) ultimately prevent propagation of action potential 6) do not alter resting membrane potential 7) increase threshold potential

Factors affecting local anesthetic action Effect of pH charged (cationic) form binds to receptor site uncharged form penetrates membrane ,efficacy of drug can be changed by altering extracellular or intracellular pH

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

Effect of protein binding - increased binding increases duration of action Effect of diffusibility - increased diffusibility = decreased time of onset Effect of vasodilator activity - greater vasodilator activity = decreased potency and decreased duration of action

FIBER SIZE AND FUNCTION α: (dia 12-20um; cond vel 70-120m/s) largest, afferent to and efferent from muscles and joints. Actions: motor function, proprioception, reflex activity. β: (dia 5-12um; 30-70m/s) large as A-alpha, afferent to and efferent from muscles and joints. Actions: motor proprioception, touch, pressure, touch and pressure. γ: (dia 3-6um; 15-30m/s) muscle spindle tone. δ: (dia 2-5um; 12-30m/s) thinnest, pain and temperature. Signal tissue damage.

B fibers: (dia – 2-5um) Myelinated preganglionic autonomic B fibers: (dia – 2-5um) Myelinated preganglionic autonomic. Innervate vascular smooth muscle. Though myelinated, they are more readily blocked by LA than C fibers.

C fibers: (dia 0. 4-1. 2 um) Nonmyelinated, very small nerves C fibers: (dia 0.4-1.2 um) Nonmyelinated, very small nerves. Smallest nerve fibers, slow transmission. Transmit dull pain and temperature, post-ganglionic autonomic. * Both A-d and C fibers transmit pain and are blocked by the same concentration of LA.

Susceptibility to block by local anesthetics of types of nerve fibers In general, small nerve fibers are more susceptible than large fibers; however, the type of fiber degree of myelination fiber length and frequency- dependence are also important in determining susceptibility

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 Essentially all systemic toxic reactions associated with local anesthetics are 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.

Hypersensitivity. Some patients are hypersensitive (allergic) to some local anesthetics. Although such allergies are very rare, a careful patient history should be taken in an attempt to identify the presence of an allergy. 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.

Central Nervous System Toxicities. Local anesthetics, if absorbed systematically in excessive amounts, can cause central nervous system (CNS) excitement or, if absorbed in even higher amounts, can cause CNS depression.

CNS toxicity cont Excitement. Tremors, shivering, and convulsions characterize the CNS excitement. Depression. The CNS depression is characterized by respiratory depression and, if enough drug is absorbed, respiratory arrest.

Cardiovascular Toxicities 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 vasoconstrictive Hypotension and a certain type of abnormal heartbeat (atrioventricular block) characterize such depression. These may ultimately result in both cardiac and respiratory arrest.

Signs of toxicity occur on a continuum Signs of toxicity occur on a continuum. From early to late stages of toxicity, these signs are: circum-oral and tongue numbness, lightheadedness, tinnitus, visual disturbances, muscular twitching, convulsions, unconsciousness, coma, respiratory arrest, then cardiovascular collapse.

Types of Local Anesthesia Local Infiltration (Local 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. Local infiltration is used primarily for surgical procedures involving a small area of tissue (for example, suturing a cut).

Topical Block. A topical block is accomplished by applying the anesthetic agent to mucous membrane surfaces and in that way blocking the nerve terminals in the mucosa. This technique is often used during examination procedures involving the respiratory tract. The anesthetic agent is rapidly absorbed into the bloodstream. For topical application (that is, to the skin), the local anesthetic is always used without epinephrine. The topical block easily anesthetizes the surface of the cornea (of the eye) and the oral mucosa.

Surface Anesthesia. This type of anesthesia is accomplished by the application of a local anesthetic to skin or mucous membranes. Surface anesthesia is used to relieve itching, burning, and surface pain (for example, as seen in minor sunburns).

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.

Peridural Anesthesia. This type of anesthesia is accomplished by injecting a local anesthetic into the peridural space. The peridural space is one of the coverings of the spinal cord.

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. There is variable response between LA and the location of injection as to whether vasoconstrictors increase duration of action. 1:200,000 epinephrine appears to be the best vasoconstrictor.