Dental Anesthesia Lecture Notes PDF

# Dental Anesthesia ## Lecture 2: Pharmacology of Local Anesthetics **Asst. Prof. Dr. Nuri Mert Tayşi** Istanbul University- Cerrahpasa Dentistry Faculty Oral and Maxillofacial Surgery Department ### Key Components of Local Anesthetics - All local anesthetics consist of three principal component...

# Dental Anesthesia ## Lecture 2: Pharmacology of Local Anesthetics **Asst. Prof. Dr. Nuri Mert Tayşi** Istanbul University- Cerrahpasa Dentistry Faculty Oral and Maxillofacial Surgery Department ### Key Components of Local Anesthetics - All local anesthetics consist of three principal components: 1. **Lipophilic aromatic ring** 2. **The intermediate chain** 3. **Hydrophilic terminal amine** | Component | Description | Effects | |---|---|---| | Lipophilic aromatic ring | The lipophilic portion of the molecule that penetrates the nerve, determining anesthetic potency. | The greater the lipid solubility of the anesthetic molecule, the greater the potency of the drug. | | Intermediate chain | Determines if the local anesthetic is an ester or an amide, impacting the course of biotransformation. Ester local anesthetics are hydrolyzed by appropriate esterases, and amide local anesthetics generally require enzymatic breakdown by the liver. | | | Hydrophilic terminal amine | The hydrophilic portion of the molecule; it is the active form in the cartridge and binds to the receptor sites on the nerve membrane. | | ### Routes of Delivery - There are two major routes of delivery of local anesthetic drugs, **topical** and **submucosal injection**. | Route | Description | Advantages | Disadvantages | |---|---|---|---| | Topical | Drugs applied to the surface of mucosal tissues that produce local insensibility to pain. Topical anesthetic agents are prepared in higher concentrations than injectable anesthetics to facilitate diffusion of the drug through the mucous membranes. | Higher concentrations facilitate diffusion. Easy to apply. | More risk for toxicity if used excessively. | | Submucosal injection | Local anesthetics are more effective than topical routes of administration because the local anesthetic solution is injected and placed in close proximity to the nerve tract of the area to be anesthetized. | More effective because of direct administration close to the nerve. | | ### Pharmacodynamics of Local Anesthetic Drugs - **Pharmacodynamics** refers to the physiological effects of drugs on the body and the mechanisms of drug action and its relationship between drug concentration and effect. - Synthetic local anesthetics are prepared as weak bases and during manufacturing precipitate as powdered unstable solids that are poorly soluble in water. - They are combined with an acid to form a salt (hydrochloride salt) to render them water-soluble; these can be dissolved in sterile water or saline, creating a stable, injectable anesthetic solution. ### The Role of pH - The pH of the body tissue is 7.4, and the ideal pKa of an anesthetic should be 7.4, indicating that 50% of the molecules are uncharged base and quick diffusion through the lipid membrane would occur. - However, the pka of all local anesthetics have values greater than 7.5 except topical benzocaine which is 3.5, and have a pH of approximately 5 to 6 in plain solutions and lower with vasoconstrictors; therefore a greater proportion of the molecules exist in the quaternary water-soluble form when injected into tissue having normal pH of 7.4. - The higher the pKa of the anesthetic, the lower the concentration of uncharged base molecules. This causes slower diffusion into the nerve cell and a slower onset of action of the local anesthetic. ### Infection and Anesthesia - Adequate blockade of the nerve is more difficult to achieve in inflamed or infected tissues because of the relatively small number of molecules able to cross the nerve sheath (RN) and the increased absorption of the remaining anesthetic molecules into dilated blood vessels in this region. Although a potential problem in all aspects of dental practice, this situation is seen most often in endodontics. - The acidic environment associated with an active infection causes a much lower tissue pH in the vicinity of 5-6, which favors the quaternary water-soluble configuration and the amount of free base is reduced even further, leaving fewer base molecules to penetrate the nerve. - The selection of an anesthetic with a lower pKa such as mepivacaine (pKa 7.7), would most likely provide more effective anesthesia than bupivacaine (pKa 8.1) ### Classification of Local Anesthetics - Local anesthetic agents are divided chemically into two major groups: the **esters** and the **amides**. | Group | Example | |---|---| | **Esters** | Procaine, Tetracaine, Benzocaine, Chloroprocaine | | **Amides** | Lidocaine, Mepivacaine, Bupivacaine, Prilocaine, Articaine | ### Metabolism of Local Anesthetics - The elimination half-life of a local anesthetic is the period of time it takes for 50% of the drug to be metabolized/removed from the body. - The first half-life removes 50% of the anesthetic from the bloodstream, the second half-life removes another 25%, the third half-life another 12%, the next half-life removes another 6%, and so on until the drug is completely removed from the body. **Ester Local Anesthetics** - Esters, are hydrolyzed in the plasma by the enzyme pseudocholinesterase, and by liver esterases. - Esters include benzocaine, tetracaine, and procaine. - Injectable esters are no longer manufactured in dental cartridges for use in dentistry because of their high potential for evoking allergic reactions. **Amid Local Anesthetics** - Amides include lidocaine, mepivacaine, prilocaine, articaine, and bupivacaine. - Amides are primarily metabolized in the liver, and the process is much more complex than for esters. **Articaine** - Articaine is also an amide but contains is rapidly metabolized in blood by plasma cholinesterase. - Articaine's major metabolite is articainic acid. It is inactive as a local anesthetic, and systemic toxicity has not been observed. ### Composition of Local Anesthetic Solutions - In addition to the local anesthetic agents, the dental cartridge may contain several other ingredients such as: * **Vasoconstrictors:** there are mainly two vasoconstrictors currently added to local anesthetic solutions world wide. All local anesthetics (except cocaine) are vasodilators, and vasoconstrictors are added to local anesthetic solutions to delay the absorption of local anesthetics, which reduces the potential for systemic toxicity and prolongs the duration of action. Because vasoconstrictors counteract the vasodilatory properties of local anesthetics, they are also beneficial for providing hemostasis. * **Vasoconstrictor preservative:** Sodium bisulfite, metabisulfite, or acetone sodium bisulfite is only added to local anesthetic solutions that contain vasoconstrictors. Since vasoconstrictors are unstable and have a short shelf life, sodium bisulfite is added to delay the deterioration of the vasoconstrictor. Sodium bisulfite is manufactured as an acid salt rendering it soluble in water and decreasing the pH of the solution, making it significantly more acidic than the same solution without a vasoconstrictor. Local anesthetic solutions that are more acidic have a greater quantity of charged cation molecules (RNH+) than the uncharged base (anion) molecules (RH). This slows the efficiency of the local anesthetic solution to diffuse into the axoplasm, delaying the onset of action. * **Sodium hydroxide:** Sodium hydroxide is a buffer that alkalinizes, or adjusts, the pH of the solution between 6 and 7. * **Sodium chloride:** Sodium chloride is a buffer which when added to a local anesthetic creates an injectable isotonic solution. ### Ester-Type Local Anesthetics #### Procaine HCl - Procaine (Novocain) was the first synthetic injectable local anesthetic and was used routinely in dentistry until amide local anesthetics became available. - Procaine produces the greatest vasodilating properties of all local anesthetics and provides no pulpal anesthesia. #### Benzocaine - One of the more common and widely used topical anesthetics. It is available in gel, cream, ointment, lozenge, liquid solution, spray, and patch. - The most commonly used concentration used in dentistry is 20%, although it is available in concentrations ranging from 6% to 20%. #### Tetracaine - A long-duration ester local anesthetic that can be injected or applied topically. - Onset of action after topical application is slow. - Duration of action is approximately 45 minutes after topical application. - Metabolized in plasma and the liver by plasma pseudocholinesterase at a slower rate than procaine. ### Amid-Type Local Anesthetics #### Lidocaine - Lidocaine was the first amide local anesthetic suitable for nerve blocks in dentistry. - Lidocaine has anticonvulsant properties and may be used to terminate or decrease the duration of grand mal and petit mal seizures. These anticonvulsant properties occur at blood levels below that of which lidocaine produces seizure activity in an overdose. - Patients may experience initial sedative effects from lidocaine compared to other local anesthetic agents. #### Mepivacaine HCl - Pharmacologically like lidocaine, mepivacaine is xylidine derivative. - Mepivacaine is available in two different formulations: 3% mepivacaine plain, and 2% mepivacaine 1: 20,000 levonordefrin. - It is therefore a good alternative if the use of a vasoconstrictor is contraindicated. #### Prilocaine HCl - Prilocaine is a toluidine derivative - Prilocaine is much less toxic (approximately half) than lidocaine, and slightly less toxic than mepivacaine and articaine. #### Articaine - Pharmacologically, articaine is derived from thiophene, which makes it different from other amide anesthetics and allows better lipid solubility. This gives the molecule better diffusion. - Amides that are primarily metabolized in the liver have a longer half-life, increasing the risk for systemic toxicity. Another basic property of articaine that differs among the other amides is that it contains an extra ester linkage. This causes articaine to be hydrolyzed by plasma esterase as well as enzymes in the liver. This gives the agents being rapidly metabolise. - Articaine's major metabolite is articainic acid. It is inactive as a local anesthetic, and systemic toxicity has not been observed. #### Bupivacaine - With the highest pKa of the amide anesthetics, bupivacaine has a slightly slower onset of action, but the duration of anesthesia is almost twice that of lidocaine. - Bupivacaine is not recommended for use on patients who are prone to self-mutilation (patients with special needs and young children). This is a summary of the information contained in the images you provided. Let me know if you have any other images or questions.