Local anesthetic

LAs are of 2 types: • Clinical LAs: • amino amide LAs • amino ester LAs • Synthetic LAs • Cocaine derivatives Synthetic cocaine-derived LAs differ from cocaine because they have a much lower abuse potential and do not cause hypertension vasoconstriction (with few exceptions). The suffix "-caine" at the ends of these medication names is derived from the word "cocaine", because cocaine was formerly used as a local anesthetic. == Examples ==

Short Duration of Action and Low Potency • Benzocaine • Procaine • Chloroprocaine • Cocaine Medium Duration of Action and Medium Potency • Articaine • Lidocaine • Prilocaine High Duration and High Potency • Tetracaine • Bupivacaine • Cinchocaine • Ropivacaine == Medical uses ==

Local anesthetics may be used to prevent and/or treat acute pain, to treat chronic pain, and as a supplement to general anesthesia. They are used in various techniques of local anesthesia such as: • Topical anesthesia (surface anesthesia) • Topical administration of cream, gel, ointment, liquid, or spray of anesthetic dissolved in DMSO or other solvents/carriers for deeper absorption • Infiltration • Brachial plexus block • Epidural block (extradural) • Spinal anesthesia (subarachnoid block) • Iontophoresis • Diagnostic purposes (e.g. dibucaine) • Anti-arrhythmic agents (e.g. lidocaine). Acute pain Even though acute pain can be managed using analgesics, conduction anesthesia may be preferable because of superior pain control and fewer side effects. For purposes of pain therapy, LA drugs are often given by repeated injection or continuous infusion through a catheter. LA drugs are also often combined with other agents such as opioids for synergistic analgesic action. Low doses of LA drugs can be sufficient so that muscle weakness does not occur and patients may be mobilized. Some typical uses of conduction anesthesia for acute pain are: Chronic pain Chronic pain is a complex and often serious condition that requires diagnosis and treatment by an expert in pain medicine. LAs can be applied repeatedly or continuously for prolonged periods to relieve chronic pain, usually in combination with medication such as opioids, NSAIDs, and anticonvulsants. Though it can be easily performed, repeated local anesthetic blocks in chronic pain conditions are not recommended as there is no evidence of long-term benefits. Surgery Virtually every part of the body can be anesthetized using conduction anesthesia. However, only a limited number of techniques are in common clinical use. Sometimes, conduction anesthesia is combined with general anesthesia or sedation for the patient's comfort and ease of surgery. However, many anesthetists, surgeons, patients and nurses believe that it is safer to perform major surgeries under local anesthesia than general anesthesia. Typical operations performed under conduction anesthesia include: Diagnostic tests Diagnostic tests such as bone marrow aspiration, lumbar puncture (spinal tap) and aspiration of cysts or other structures are made to be less painful upon administration of local anesthetic before insertion of larger needles. Other uses Local anesthesia is also used during insertion of IV devices, such as pacemakers and implantable defibrillators, ports used for giving chemotherapy medications and hemodialysis access catheters. Topical anesthesia, in the form of lidocaine/prilocaine (EMLA) is most commonly used to enable relatively painless venipuncture (blood collection) and placement of intravenous cannulae. It may also be suitable for other kinds of punctures such as ascites drainage and amniocentesis. Surface anesthesia also facilitates some endoscopic procedures such as bronchoscopy (visualization of the lower airways) or cystoscopy (visualization of the inner surface of the bladder) == Side effects ==

Localized side effects Edema of tongue, pharynx and larynx may develop as a side effect of local anesthesia. This could be caused by a variety of reasons including trauma during injection, infection, an allergic reaction, haematoma or injection of irritating solutions such as cold-sterilization solutions. Usually there is tissue swelling at the point of injection. This is due to puncturing of the vein which allows the blood to flow into loose tissues in the surrounding area. Blanching of the tissues in the area where the local anesthetic is deposited is also common. This gives the area a white appearance as the blood flow is prevented due to vasoconstriction of arteries in the area. The vasoconstriction stimulus gradually wears off and subsequently the tissue returns to normal in less than two hours. The side effects of inferior alveolar nerve block include feeling tense, clenching of the fists and moaning. The duration of soft tissue anesthesia is longer than pulpal anesthesia and is often associated with difficulty eating, drinking and speaking. There is risk of accidental damage to local blood vessels during injection of the local anesthetic solution. This is referred to as haematoma and could result in pain, trismus, swelling and/or discoloration of the region. The density of tissues surrounding the injured vessels is an important factor for hematoma. There is greatest chance of this occurring in a posterior superior alveolar nerve block or in a pterygomandibular block. Giving local anesthesia to patients with liver disease can have significant consequences. Thorough evaluation of the disease should be carried out to assess potential risk to the patient as in significant liver dysfunction, the half-life of amide local anesthetic agents may be drastically increased thus increasing the risk of overdose. Local anesthetics and vasoconstrictors may be administered to pregnant patients however it is very important to be extra cautious when giving a pregnant patient any type of drug. Lidocaine can be safely used but bupivacaine and mepivacaine should be avoided. Consultation with the obstetrician is vital before administering any type of local anesthetic to a pregnant patient. --> Emotional reactions When patients are emotionally affected in the form of nervousness or fear, it can lead to vasovagal collapse. This is the anticipation of pain during administration that activates the parasympathetic nervous system while inhibiting the orthosympathetic nervous system. What results is a dilation of arteries in muscles which can lead to a reduction in circulating blood volume inducing a temporary shortness of blood flow to the brain. Notable symptoms include restlessness, visibly looking pale, perspiration and possible loss of consciousness. In severe cases, clonic cramps resembling an epileptic insult may occur. A profound depression of brain functions may occur at even higher concentrations which may lead to coma, respiratory arrest, and death. Such tissue concentrations may be due to very high plasma levels after intravenous injection of a large dose. Another possibility is direct exposure of the central nervous system through the cerebrospinal fluid, i.e., overdose in spinal anesthesia or accidental injection into the subarachnoid space in epidural anesthesia. Cardiovascular system Cardiac toxicity can result from improper injection of agent into a vessel. Even with proper administration, it is inevitable for some diffusion of agent into the body from the site of application due to unforeseeable anatomical idiosyncrasies of the patient. Toxicity from anesthetic combinations is additive. Therefore, amides can be used as alternatives in those patients. Nonallergic reactions may resemble allergy in their manifestations. In some cases, skin tests and provocative challenge may be necessary to establish a diagnosis of allergy. Also cases of allergy to paraben derivatives occur, which are often added as preservatives to local anesthetic solutions. Methemoglobinemia Methemoglobinemia is a process where iron in hemoglobin is altered, reducing its oxygen-carrying capability, which produces cyanosis and symptoms of hypoxia. Exposure to aniline group chemicals such as benzocaine, lidocaine, and prilocaine can produce this effect, especially benzocaine. However, the evidence at this point is still limited. Though most case reports to date have recorded most common use of Intralipid, other emulsions, such as Liposyn and Medialipid, have also been shown effective. Ample supporting animal evidence One published case has been reported of successful treatment of refractory cardiac arrest in bupropion and lamotrigine overdose using lipid emulsion. The design of a 'homemade' lipid rescue kit consisting of a standard lipid injection, IV tubing, syringes, and needles has been described. Although lipid rescue mechanism of action is not completely understood, the added lipid in the blood stream may act as a sink, allowing for the removal of lipophilic toxins from affected tissues. This theory is compatible with two studies on lipid rescue for clomipramine toxicity in rabbits and with a clinical report on the use of lipid rescue in veterinary medicine to treat a puppy with moxidectin toxicosis. == Mechanism of action ==

All LAs are membrane-stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes (like nociceptors). Though many other drugs also have membrane-stabilizing properties, not all are used as LAs (propranolol, for example, though it has LA properties). LA drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Local anesthetic drugs bind more readily to sodium channels in an activated state, thus onset of neuronal blockade is faster in rapidly firing neurons. This is referred to as state-dependent blockade. LAs are weak bases and are usually formulated as the hydrochloride salt to render them water-soluble. At a pH equal to the protonated base's pKa, the protonated (ionized) and unprotonated (unionized) forms of the molecule exist in equimolar amounts, but only the unprotonated base diffuses readily across cell membranes. Once inside the cell, the local anesthetic will be in equilibrium, with the formation of the protonated (ionized) form, which does not readily pass back out of the cell. This is referred to as "ion-trapping". In the protonated form, the molecule binds to the LA binding site on the inside of the ion channel near the cytoplasmic end. Most LAs work on the internal surface of the membrane - the drug has to penetrate the cell membrane, which is achieved best in the nonionised form. This is exemplified by the permanently ionised LA RAC 421-II which cannot diffuse across the cell membrane but, if injected into the cytosol of a nerve fibre, can induce NaKATPase blockage and anesthetic effects. Acidosis such as caused by inflammation at a wound partly reduces the action of LAs. This is partly because most of the anesthetic is ionized and therefore unable to cross the cell membrane to reach its cytoplasmic-facing site of action on the sodium channel. Sensitivity of nerve fibers to local anesthetics For most patients, administration of local anesthetics causes the sensation of pain to be lost first, followed by temperature, touch, deep pressure, and finally motor function. The sensitivity of nerve fibers to blockade depends on a combination of diameter and myelination. Their different sensitivities to LA blockade is termed differential blockade. Myelinated fibers are more sensitive to blockade as they are interrupted by nodes of Ranvier, thus interruption of only consecutive nodes of Ranvier will prevent action potential propagation. In turn, in unmyelinated nerves, an entire length needs to be blocked. Regarding diameter, the generally accepted principle is that susceptibility to local anesthesia depends inversely on fiber diameter. In general, autonomic fibers Type B fibers, small unmyelinated type C (pain sensation), and small myelinated Aδ fibers(pain and temperature sensations) are blocked before the larger myelinated Aγ, Aβ, and Aα fibers (mediating postural, touch, pressure, and motor information). == Techniques ==

Local anesthetics can block almost every nerve between the peripheral nerve endings and the central nervous system. The most peripheral technique is topical anesthesia to the skin or other body surface. Small and large peripheral nerves can be anesthetized individually (peripheral nerve block) or in anatomic nerve bundles (plexus anesthesia). Spinal anesthesia and epidural anesthesia merge into the central nervous system. Injection of LAs is often painful. A number of methods can be used to decrease this pain, including buffering of the solution with bicarbonate and warming. Clinical techniques include: • Surface anesthesia is the application of an LA spray, solution, or cream to the skin or a mucous membrane; the effect is short lasting and is limited to the area of contact. • Infiltration anesthesia is infiltration of LA into the tissue to be anesthetized; surface and infiltration anesthesia are collectively topical anesthesia • Field block is subcutaneous injection of an LA in an area bordering on the field to be anesthetized. • Peripheral nerve block is injection of LA in the vicinity of a peripheral nerve to anesthetize that nerve's area of innervation. • Plexus anesthesia is injection of LA in the vicinity of a nerve plexus, often inside a tissue compartment that limits the diffusion of the drug away from the intended site of action. The anesthetic effect extends to the innervation areas of several or all nerves stemming from the plexus. • Epidural anesthesia is an LA injected into the epidural space, where it acts primarily on the spinal nerve roots; depending on the site of injection and the volume injected, the anesthetized area varies from limited areas of the abdomen or chest to large regions of the body. • Spinal anesthesia is an LA injected into the cerebrospinal fluid, usually at the lumbar spine (in the lower back), where it acts on spinal nerve roots and part of the spinal cord; the resulting anesthesia usually extends from the legs to the abdomen or chest. • Intravenous regional anesthesia (Bier's block) is when blood circulation of a limb is interrupted using a tourniquet (a device similar to a blood-pressure cuff), then a large volume of LA is injected into a peripheral vein. The drug fills the limb's venous system and diffuses into tissues, where peripheral nerves and nerve endings are anesthetized. The anesthetic effect is limited to the area that is excluded from blood circulation and resolves quickly once circulation is restored. • Local anesthesia of body cavities includes intrapleural anesthesia and intra-articular anesthesia. • Transincision (or transwound) catheter anesthesia uses a multilumen catheter inserted through an incision or wound and aligned across it on the inside as the incision or wound is closed, providing continuous administration of local anesthetic along the incision or wounds Dental-specific techniques include: Vazirani–Akinosi technique The Vazirani–Akinosi technique is also known as the closed-mouth mandibular nerve block. It is mostly used in patients who have limited opening of the mandible or in those that have trismus; spasm of the muscles of mastication. The nerves which are anesthetised in this technique are the inferior alveolar, incisive, mental, lingual and mylohyoid nerves. Dental needles are available in two lengths, short and long. As Vazirani–Akinosi is a local anesthetic technique which requires penetration of a significant thickness of soft tissues, a long needle is used. The needle is inserted into the soft tissue which covers the medial border of the mandibular ramus, in region of the inferior alveolar, lingual and mylohyoid nerves. The positioning of the bevel of the needle is very important as it must be positioned away from the bone of the mandibular ramus and instead towards the midline. Intraligamentary Infiltration Intraligamentary infiltration, also known as periodontal ligament injection or intraligamentary injection (ILI), is known as "the most universal of the supplemental injections". ILIs are usually administered when inferior alveolar nerve block techniques are inadequate or ineffective. ILIs are purposed for: • Single-tooth anesthesia • Low anesthetic dose • Contraindication for systemic anesthesia • Presence of systemic health problems ILI utilization is expected to increase because dental patients prefer fewer soft tissue anesthesia and dentists aim to reduce administration of traditional inferior alveolar nerve block (INAB) for routine restorative procedures. Injection methodology: The periodontal ligament space provides an accessible route to the cancellous alveolar bone, and the anesthetic reaches the pulpal nerve via natural perforation of intraoral bone tissue. Advantages of ILI over INAB: rapid onset (within 30 seconds), small dosage required (0.2–1.0 mL), limited area of numbness, lower intrinsic risks such as neuropathy, hematoma, trismus/jaw sprain and self-inflicted periodontal tissue injury, as well as decreased cardiovascular disturbances. Its usage as a secondary or supplementary anesthesia on the mandible has reported a high success rate of above 90%. Disadvantages: Risk of temporary periodontal tissue damage, likelihood of bacteriemia and endocarditis for at-risk populations, appropriate pressure and correct needle placement are imperative for anesthetic success, short duration of pulpal anesthesia limits the use of ILIs for several restorative procedures that require longer duration, • Administration of soft tissue anesthesia is recommended prior to ILI administration. This helps to enhance patient comfort. • Needle gauges of sizes 27-gauge short or 30-gauge ultra-short needle are usually utilized. • The needle is inserted along the long axis, at a 30 degree angle, of the mesial or distal root for single rooted teeth and on the mesial and distal roots of multi-rooted teeth. Bevel orientation toward the root provides easier advancement of the needle apically. • When the needle reaches between the root and crestal bone, significant resistance is experience. • Anesthetic deposition is recommended at 0.2 mL, per root or site, over minimally 20 seconds. • For its success, the anesthetic must be administered under pressure. It must not leak out of the sulcus into the mouth. • Withdraw needle for minimally 10–15 seconds to permit complete deposition of solution. This can be slower than other injections as there is pressure build-up from the anesthetic administration. • Blanching of the tissue is observed and may be more evident when vasoconstrictors are used. It is caused by a temporary obstruction of blood flow to the tissue. thus permitting larger amounts of anesthetic solution to be delivered during ILIs without increased tissue damage. Things to note: • ILIs are not recommended for patients with active periodontal inflammation. • ILIs should not be administered at tooth sites with 5 mm or more of periodontal attachment loss. Gow-Gates Technique Gow-Gates technique is used to provide anesthetics to the mandible of the patient's mouth. With the aid of extra and intraoral landmarks, the needle is injected into the intraoral latero-anterior surface of the condyle, steering clear below the insertion of the lateral pterygoid muscle. The extraoral landmarks used for this technique are the lower border of the ear tragus, corners of the mouth and the angulation of the tragus on the side of the face. Biophysical forces (pulsation of the maxillary artery, muscular function of jaw movement) and gravity will aid with the diffusion of anesthetic to fill the whole pterygomandibular space. All three oral sensory parts of the mandibular branch of the trigeminal nerve and other sensory nerves in the region will come in contact with the anesthetic and this reduces the need to anesthetise supplementary innervation. In comparison to other regional block methods of anestheising the lower jaw, the Gow-Gates technique has a higher success rate in fully anesthetising the lower jaw. One study found that out of 1,200 patients receiving injections through the Gow-Gates technique, only 2 of them did not obtain complete anesthesia. == Types ==

. A cartridge of LA fits into the disposable needle, which can be locked when not in use and can be separated from the handle. Local anesthetic solutions for injection typically consist of: • The local anesthetic agent itself • A vehicle, which is usually water-based or just sterile water • Vasoconstrictor possibly (see below) • Reducing agent (antioxidant), e.g. if epinephrine is used, then sodium metabisulfite is used as a reducing agent • Preservative, e.g. methylparaben • Buffer Esters are prone to producing allergic reactions, which may necessitate the use of an amide. The names of each locally clinical anesthetic have the suffix "-caine". Most ester LAs are metabolized by pseudocholinesterase, while amide LAs are metabolized in the liver. This can be a factor in choosing an agent in patients with liver failure, although since cholinesterases are produced in the liver, physiologically (e.g. very young or very old individual) or pathologically (e.g. cirrhosis) impaired hepatic metabolism is also a consideration when using esters. Sometimes, LAs are combined, e.g.: • Lidocaine/prilocaine (EMLA, eutectic mixture of local anesthetic) • Lidocaine/tetracaine (Rapydan) • TAC LA solutions for injection are sometimes mixed with vasoconstrictors (combination drug) to increase the duration of local anesthesia by constricting the blood vessels, thereby safely concentrating the anesthetic agent for an extended duration, as well as reducing hemorrhage. Because the vasoconstrictor temporarily reduces the rate at which the systemic circulation removes the local anesthetic from the area of the injection, the maximum doses of LAs when combined with a vasoconstrictor is higher compared to the same LA without any vasoconstrictor. Occasionally, cocaine is administered for this purpose. Examples include: • Prilocaine hydrochloride and epinephrine (trade name Citanest Forte) • Lidocaine, bupivacaine, and epinephrine (recommended final concentrations of 0.5, 0.25, and 0.5%, respectively) • Iontocaine, consisting of lidocaine and epinephrine • Septocaine (trade name Septodont), a combination of articaine and epinephrine One combination product of this type is used topically for surface anaesthesia, TAC (5–12% tetracaine,1/2000 (0.05%, 500 ppm, per mille) adrenaline, 4 or 10% cocaine). Using LA with vasoconstrictor is safe in regions supplied by end arteries. The commonly held belief that LA with vasoconstrictor can cause necrosis in extremities such as the nose, ears, fingers, and toes (due to constriction of end arteries), is invalidated, since no case of necrosis has been reported since the introduction of commercial lidocaine with epinephrine in 1948. Ester group • Benzocaine • Chloroprocaine • Cocaine • Cyclomethycaine • Dimethocaine (Larocaine) • Oxybuprocaine • Piperocaine • Propoxycaine • Procaine (Novocaine) • Proparacaine • Tetracaine (Amethocaine) Amide group • Articaine • Bupivacaine • Cinchocaine (Dibucaine) • Etidocaine • Levobupivacaine • Lidocaine (Lignocaine) • Mepivacaine • Prilocaine • Ropivacaine • Trimecaine Naturally derived • Saxitoxin • Neosaxitoxin • Tetrodotoxin • Menthol • Eugenol • Cocaine • Spilanthol Most naturally occurring local anesthetics with the exceptions of menthol, eugenol and cocaine are neurotoxins, and have the suffix -toxin in their names. Cocaine binds the intracellular side of the channels while saxitoxin, neosaxitoxin and tetrodotoxin bind to the extracellular side of sodium channels. == History ==

In Peru, the ancient Incas are believed to have used the leaves of the coca plant as a local anesthetic in addition to its stimulant properties. It was also used for slave payment and is thought to play a role in the subsequent destruction of Incas culture when Spaniards realized the effects of chewing the coca leaves and took advantage of it. Shortly after the first use of cocaine for topical anesthesia, blocks on peripheral nerves were described. Brachial plexus anesthesia by percutaneous injection through axillary and supraclavicular approaches was developed in the early 20th century. The search for the most effective and least traumatic approach for plexus anesthesia and peripheral nerve blocks continues to this day. In recent decades, continuous regional anesthesia using catheters and automatic pumps has evolved as a method of pain therapy. Intravenous regional anesthesia was first described by August Bier in 1908. This technique is still in use and is remarkably safe when drugs of low systemic toxicity such as prilocaine are used. Spinal anesthesia was first used in 1885, but not introduced into clinical practice until 1899, when August Bier subjected himself to a clinical experiment in which he observed the anesthetic effect, but also the typical side effect of postpunctural headache. Within a few years, spinal anesthesia became widely used for surgical anesthesia and was accepted as a safe and effective technique. Although atraumatic (noncutting-tip) cannulae and modern drugs are used today, the technique has otherwise changed very little over many decades. Epidural anesthesia by a caudal approach had been known in the early 20th century, but a well-defined technique using lumbar injection was not developed until 1921, when Fidel Pagés published his article "Anestesia Metamérica". This technique was popularized in the 1930s and 1940s by Achile Mario Dogliotti. With the advent of thin, flexible catheters, continuous infusion and repeated injections have become possible, making epidural anesthesia still a highly successful technique. Besides its many uses for surgery, epidural anesthesia is particularly popular in obstetrics for the treatment of labor pain. == See also ==