What Is a Topical Anesthetic?

Local anesthetics (local anaesthetics) are a class of medicines that can block the occurrence and transmission of sensory nerve impulses locally and reversibly, referred to as "local anesthetics". In the case of maintaining consciousness, it can reversibly cause local tissue pain to disappear. In general, the effects of local anesthetics are limited to the site of administration and quickly disappear as the drug diffuses from the site of administration.

Drug Name: Local anesthetic
Foreign name: local anaesthetics

Whether prescription drugs: prescription
Main indications: Reversible loss of local tissue pain

Introduction to Local Anesthetics

The earliest local anesthetic used was the alkaloid cocaine proposed from coca leaves in South America, but its use was limited due to its high toxicity after absorption. In 1904, according to the chemical structural characteristics of cocaine, the low-toxicity of procaine (procaine) was artificially synthesized, and its use range continued to expand. Lidocaine, synthesized in 1943, is typical of amide-type local anesthetics.

According to the type of chemical structure, local anesthetics can be divided into: parabens (procaine, benzocaine), amides (lidocaine, bupivacaine), amino ethers and amino ketones Class (Dakronin) and so on.

Application method of local anesthetic local anesthetic

Topical anaesthesia

2. infiltration anaesthesia

3. Conductive anesthesia (conduction anaesthesia, block anaesthesia)

4. Subarachnoid anesthesia (spine, spinal anesthesia, subarachnoid anaesthesia, spinal anaesthesia)

5. Epidural anaesthesia

Structure-activity relationship of local anesthetics

The chemical structure of common local anesthetics consists of three parts, namely aromatic ring, middle chain and amine group. The middle chain can be ester or amide chain. According to the structure of the intermediate chain, the commonly used local anesthetics can be divided into two categories: the first category is esters, which have -COO- groups in the structure. The drugs belonging to this category are procaine, tetracaine, etc .; The second group is amides, which have -CONH- group in the structure. The drugs belonging to this group are lidocaine and bupivacaine.

There are many types of chemical structures of local anesthetics. According to the clinical application of local anesthetics, such as esters, amides, and ketones, their chemical structures can be summarized into three parts: lipophilic part, intermediate chain and hydrophilic part.

1. The lipophilic part can be divided into aromatic hydrocarbons and aromatic heterocyclic rings, but the role of benzene ring is strong, which guarantees that the drug molecules have considerable fat solubility. The hydrophilic amine moiety is usually a tertiary amine structure (because it is less irritating), which not only ensures that the drug molecule has a certain water solubility to facilitate transport, but also provides a structural basis for binding to the acceptor site of the Na + channel. Therefore, the lipophilic and hydrophilic portions of a local anesthetic must maintain an appropriate balance. This equilibrium can be described to some extent by the dissociation constant. Its order of action is:

Benzene ring pyrrole phenothia furan

When the hydroxyl group, alkoxy group and amino group are introduced into the benzene ring, the anesthetic effect is enhanced, and the local anesthetic such as butylamino group is particularly effective when the amino group is introduced in the para position.

2. The middle chain is related to the duration of action of the local anesthetic and determines the stability of the drug.

3. The n in the middle chain is preferably 2 to 3 carbon atoms. The carbon chain grows, and the effect can be extended, but the toxicity is increased.

4. The hydrophilic part is secondary amine, tertiary amine or pyrrole, pyridine, etc., tertiary amine is preferred. Alkyl groups work best with 3 to 4 carbon atoms.

5. In order to maintain a high local concentration of the drug and maintain a certain period of action, the fat solubility should not be too large, otherwise it will easily penetrate the blood vessel wall and flow with the blood to the whole body, reducing the local concentration to achieve the desired effect. However, in order to facilitate the diffusion of the preparation in a certain range of body fluids, it must have a certain degree of water solubility.

Local anesthetic

The role of local anesthetics is related to the diameter of nerve cells or nerve fibers and the anatomical characteristics of nerve tissue. The general rule is that synaptic sites in nerve fiber endings, ganglia, and central nervous system are the most sensitive to local anesthetics. Fine nerve fibers are more easily blocked than thick nerve fibers. For myelin-free sympathetic and parasympathetic ganglion fibers can be effective at low concentrations. Myelinated sensory and motor nerve fibers require high concentrations to be effective. When acting on mixed nerves, the first thing that disappears is persistent dull pain (such as tenderness), followed by transient sharp pain, followed by the disappearance of cold, temperature, touch, and pressure, followed by motor paralysis and spider web When subcutaneous membrane anesthesia, the autonomic nerve is first blocked, and then anesthesia is produced in the above order. Recovery of nerve impulses proceeds in the reverse order.

Mechanism of local anesthetics

It is currently recognized that local anesthetics block voltage-gated Na + channels on nerve cell membranes, block conduction, and produce local anesthesia. The effects of local anesthetics are frequency and voltage dependent.

Local anesthetic in vivo process

1. The amount and speed of the local anesthetic absorbed into the blood circulation after the local anesthetic is absorbed determines the blood concentration. The influencing factors are: (1) the dose of the drug; (2) the site of administration; (3) the performance of the local anesthetic; (4) the vasoconstrictor.

2. After anaesthesia is absorbed into the blood, it is first distributed to high perfusion organs such as the brain, lungs, liver, and kidneys, and then to slower blood perfusion sites such as muscle, intestines, and skin.

3 After biotransformation and elimination of local anesthetics enter the blood circulation, their metabolites are more water-soluble and are excreted from the urine. Ester local anesthetics are mainly inactivated by the hydrolysis of pseudocholinesterase, such as congenital pseudocholine If the quality of esterase is abnormal, or the amount is reduced due to cirrhosis, severe anemia, cachexia and late pregnancy, the amount of ester local anesthetic should be reduced. The law of transformation and degradation of amide drugs is not completely clear. It is mainly metabolized in the endoplasmic reticulum of liver cells. Therefore, the dosage of patients with liver dysfunction should be reduced.

Local anesthetic

1. Procaine is one of the commonly used local anesthetics. Weak penetration into mucous membranes. Generally not used for surface anesthesia, local injection is often used for infiltration anesthesia, conduction anesthesia, subarachnoid anesthesia and epidural anesthesia. Procaine can be hydrolyzed by esterase in plasma and converted into p-aminobenzoic acid (PABA) and diethylaminoethanol. The former can counteract the antibacterial effect of sulfa drugs. Therefore, it should be avoided to be used together with sulfa drugs. Procaine can also be used for local closure of injury sites. It can sometimes cause allergic reactions, so a skin allergy test should be done before medication, but allergic reactions can still occur in people with negative skin tests. People who are allergic to this medicine can use ricloprocaine and lidocaine instead.

Chloroprocaine (chloroprocaine) uses a chemical modification method to replace the 2-position of p-aminobenzoic acid in the procaine molecule with a chlorine atom to form chloroprocaine, forming a new generation of local anesthetics, which are short-acting esters. Anesthetics have strong resistance to light, heat and humidity, and can be administered continuously without rapid drug resistance. Loprocaine is less toxic and its metabolites are not allergenic substances. No skin test is required, and clinical application is convenient and easy.

2. Lidocaine, also known as xylocaine, is the most commonly used local anesthetic. Compared with procaine at the same concentration, lidocaine has the characteristics of fast onset, strong and long-lasting effect, strong penetrating power, and large safety range. At the same time, it has no vasodilating effect and has almost no irritation to tissues. It can be used in various forms of local anesthesia, known as a general-purpose anesthetic, and is mainly used for conductive anesthesia and epidural anesthesia. This medicine can also be used for the treatment of arrhythmia. This medicine can be used for those who are allergic to procaine.

Lidocaine carbonate is a sterilized aqueous solution of lidocaine carbonate prepared by adjusting the pH of lidocaine hydrochloride with sodium bicarbonate and saturated with carbon dioxide. The critical point is 28 ° C, and no crystals precipitate below 28 ° C. Lidocaine carbonate should be used at lower room temperature, and the liquid must be injected immediately after extraction. The release of lidocaine carbonate CO2 compared with lidocaine hydrochloride has the characteristics of faster onset of anesthesia, shorter time required for block completion, no effect on block segments, and narrow safety range of blood concentration.

3 Dicaine is also called tetracaine. It has a chemical structure similar to procaine and is a lipid local anesthetic. This medicine has strong penetrating power to the mucous membrane and is often used for surface anesthesia. Eye drops with 0.5% to 1% solution, no adverse reactions such as corneal injury. This drug can also be used for conductive anesthesia, spinal anesthesia and epidural anesthesia. Because of its high toxicity, it is generally not used for infiltration anesthesia.

4 Bupivacaine, also known as marcaine, is an amide local anesthetic. Its chemical structure is similar to lidocaine. Local anesthesia is stronger than lidocaine and lasts longer. This medicine is mainly used for infiltration anesthesia, conduction anesthesia and epidural anesthesia.

Levobupivacaine (levobupivacaine) is a new type of long-acting local anesthetic. As an isomer of bupivacaine, theoretical and animal evidence has proved that it has relatively low toxicity.

5. The chemical structure of ropivacaine is similar to that of bupivacaine. It has a strong effect on blocking pain and has a weak effect on exercise. It has a short duration of action. It is less toxic to myocardium than bupivacaine and has obvious contraction of blood vessels. effect. Suitable for epidural, brachial plexus block and local infiltration anesthesia. It has almost no effect on uterine and placental blood flow and is therefore suitable for anesthesia in obstetric surgery.

Clinical Application of Local Anesthetics

1. Surface anaesthesia is a method of applying a local penetrating local anesthetic to the surface of the mucosa as needed to anesthetize the submucosal nerve endings. For superficial surgery of the mucous membranes of the eyes, nose, mouth, throat, trachea, esophagus and genitourinary tract. Tecaine is often used, such as throat spray anesthesia before ENT surgery.

2. Infiltration anaesthesia involves injecting a local anesthetic solution into the tissues under the skin or near the surgical field to anaesthetize the local nerve endings. A small amount of epinephrine can be added to the solution as needed to slow the absorption of local anesthetics and prolong the action time. The advantage of infiltration anesthesia is that the anesthesia effect is good without affecting the normal function of the body. The disadvantage is that the dosage is large and the anesthesia area is small. When large surgery is performed, systemic toxic reactions are likely to occur due to the large amount of medicine required. Lidocaine and procaine are available.

3 Conduction anaesthesia is the injection of local anesthetic near the peripheral nerve trunk to block the impulse conduction of the nerve and anaesthetize the area where the nerve is distributed. The concentration of local anesthetic required to block the neural stem is higher than that required for anesthetizing nerve endings, but the amount is small and the anesthesia area is large. Lidocaine, procaine, and bupivacaine can be selected. In order to prolong anesthesia, bupivacaine and lidocaine can also be used together.

4 Subarachnoidal anaesthesia, also called spinal anaesthesia or spinal anaesthesia, is an injection of anesthetic into the subarachnoid space of the lumbar spine to anaesthetize the spinal nerve roots at that site. Sympathetic fibers are blocked first, sensory fibers are second, and motor fibers are last. Commonly used for lower abdomen and lower limb surgery. Commonly used drugs are lidocaine, tetracaine, and procaine. The diffusion of the drug in the spinal canal is affected by the patient's position, posture, dose, injection strength and specific gravity of the solution. Procaine solutions usually have a higher specific gravity than cerebrospinal fluid. In order to control drug diffusion, it is usually formulated as a high specific gravity or low specific gravity solution. If the released cerebrospinal fluid is dissolved or a 10% glucose solution is added to the local anesthetic, the specific gravity is higher than that of the cerebrospinal fluid, and the specific gravity of the solution prepared with distilled water may be lower than the cerebrospinal fluid. When the patient is sitting or the head is high, the high specific gravity solution can diffuse to the lowest part of the dura mater. On the contrary, if the low specific gravity solution is used, there is a risk of diffusion into the cranial cavity.

The main dangers of spinal anesthesia are respiratory paralysis and decreased blood pressure. The latter is mainly due to the significant expansion of veins and venules after they lose innervation. The extent of expansion is determined by the venous pressure of the lumen. Increased venous blood volume causes a significant decrease in cardiac output and blood pressure, so maintaining adequate venous blood flow to the heart is critical. A mild head low (10 ° to 15 °) is recommended or ephedrine is used for prevention in advance.

5. Epidural anaesthesia is the injection of a medicinal solution into the epidural space. The anesthetic spreads along the nerve sheath and blocks the nerve root through the intervertebral foramen. The epidural space terminates in the foramen magnum and is not in communication with the cranial cavity. The medicinal solution does not spread to the brain tissue. There is no headache or spinal irritation in the absence of spinal anesthesia. However, the dosage of epidural anesthesia is 5-10 times larger than that of spinal anesthesia. If it is mistakenly inserted into the subarachnoid space, it can cause serious toxic reactions. Epidural anesthesia can also cause peripheral vasodilation, decreased blood pressure and cardiac depression. Ephedrine can be used for prevention and treatment. Commonly used drugs are lidocaine, bupivacaine, and ropivacaine.

6. Regional analgesia In recent years, the development of peripheral nerve block technology and local anesthetics has provided patients with more effective and effective methods for perioperative analgesia. Usually combined with opioids, it can reduce the opioids. Dosage. Local anaesthetics such as bupivacaine, levobupivacaine and ropivacaine are most widely used in regional analgesia, especially ropivacaine, which has the characteristics of sensory and motor block separation, making it a regional The medicine of choice for analgesia.

Local anesthetic adverse reactions

1. Toxicity The systemic effects of local anesthetics when the dose or concentration is too high or when the drug is mistakenly injected into the blood vessels are mainly manifested by the toxicity of the central nervous system and the cardiovascular system.

(1) Central nervous system: The effects of local anesthetics on the central nervous system are first excited and then suppressed. Central inhibitory neurons are more sensitive to local anesthetics. Due to the central nervous system's excitement and imbalance of inhibition, the central nervous system de-inhibits and excitatory symptoms appear. Convulsions caused by local anesthetics are caused by the spread of excitatory foci in the limbic system to the periphery. Intravenous diazepam can strengthen the inhibition of GABAergic neurons in the limbic system and prevent seizures. (2) Cardiovascular system: Local anesthetics have a membrane-stabilizing effect on myocardial cell membranes, which can reduce myocardial excitability after absorption. Most local anesthetics can dilate the small arteries and lower blood pressure. Therefore, when the blood concentration is too high, it can cause blood pressure to drop, and even cardiovascular reactions such as shock.

Prevention and treatment of local anesthetics

Prevention and treatment: Prevention should be given priority, the concentration of the drug and the maximum amount allowed at one time should be grasped, and a small-dose injection method should be adopted. Children, pregnant women, and patients with renal insufficiency should be appropriately reduced.

Allergic reactions are rare, and symptoms similar to excessive poisoning occur immediately after a small amount of medication. It is generally believed that esters have more allergic reactions than amides.

Prevention: Ask about the history of allergies and family history, test sensitivity before anesthesia, and give a small dose before medication. If the patient has no special complaints and abnormalities, give an appropriate amount. In addition, local anesthesia should be given appropriate barbiturates to accelerate the decomposition of local anesthetics. Once an allergic reaction occurs, the drug should be stopped immediately and rescued.