A local anesthetic is a drug that reversibly inhibits the propagation of signals along nerves. When it is used on specific nerve pathways, effects such as analgesia (loss of pain sensation) and paralysis (loss of muscle power) can be achieved. This article does not cite any references or sources. ... Nerves (yellow) Nerves redirects here. ... For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... Pain redirects here. ... Paralysed redirects here. ... For other uses of Muscles, see Muscles (disambiguation). ...

Clinical local anesthetics belong to one of two classes: aminoamide and aminoester local anesthetics. synthetic local anesthetics are structurally related to cocaine. They differ from cocaine mainly in that they have no abuse potential and do not act on the sympathoadrenergic system, i.e. they do not produce hypertension or local vasoconstriction, with the exception of Ropivacaine and Mepivacaine that do produce weak vasoconstriction. Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. ... For other forms of hypertension, see Hypertension (disambiguation). ... The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... Ropivacaine (1-propyl-2’,6’-pipecoloxylidide; Naropin®) is a long-acting local anesthetic given by injection to reduce the sensation of pain. ... Mepivacaine (IPA: ) is a local anesthetic of the amino amide type. ...

Local anesthetics vary in their pharmacological properties and they are used in various techniques of local anesthesia such as: Pharmacology (in Greek: pharmakon (φάρμακον) meaning drug, and lego (λέγω) to tell (about)) is the study of how drugs interact with living organisms to produce a change in function. ... It has been suggested that this article or section be merged with local anesthetic. ...

• Topical anesthesia (surface)
• Infiltration
• Plexus block
• Epidural (extradural) block
• Spinal anesthesia (subarachnoid block)

The local anesthetic lidocaine (lignocaine) is also used as a Class Ib antiarrhythmic drug. A topical anesthetic is a local anesthetic that is used to numb the surface of a body part. ... Lidocaine (INN) (IPA: ) or lignocaine (former BAN) (IPA: ) is a common local anesthetic and antiarrhythmic drug. ... Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress fast rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation. ...

Mechanism of action

All local anesthetics are membrane stabilizing drugs, they reversibly decrease the rate of depolarization and repolarization of excitable membranes (like neurons). Though many other drugs also have membrane stabilizing properties, all are not used as local anesthetics, for example propranolol. Local anesthetic drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the so-called 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 "open" sodium channels, thus onset of neuronal blockade is faster in neurons that are rapidly firing. This is referred to as state dependent blockade. Drawing of a cell membrane A component of every biological cell, the cell membrane (or plasma membrane) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ... Neurons (also called nerve cells) are the primary cells of the nervous system. ... Propranolol (INN) (IPA: ) is a non-selective beta blocker mainly used in the treatment of hypertension. ... For sodium in the diet, see Edible salt. ... Ion channels are pore-forming proteins that help to establish and control the small voltage gradient that exists across the plasma membrane of all living cells (see cell potential) by allowing the flow of ions down their electrochemical gradient. ... Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. ... Look up cell membrane in Wiktionary, the free dictionary. ... A. A schematic view of an idealized action potential illustrates its various phases as the action potential passes a point on a cell membrane. ...

Local anesthetics are weak bases and are usually formulated as the hydrochloride salt to render them water-soluble. At the chemical's pKa the protonated (ionised) and unprotonated (unionised) forms of the molecule exist in an equilibrium but only the unprotonated molecule diffuses readily across cell membranes. Once inside the cell the local anesthetic will be in equilibrium, with the formation of the protonated (ionised 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 local anaesthetic binding site on the inside of the ion channel near the cytoplasmic end. Acids and bases: Acid-base extraction Acid-base reaction Acid dissociation constant Acidity function Buffer solutions pH Proton affinity Self-ionization of water Acids: Lewis acids Mineral acids Organic acids Strong acids Superacids Weak acids Bases: Lewis bases Organic bases Strong bases Superbases Non-nucleophilic bases Weak bases edit In...

Acidosis such as caused by inflammation at a wound partly reduces the action of local anesthetics. This is partly because most of the anaesthetic is ionised and therefore unable to cross the cell membrane to reach its cytoplasmic-facing site of action on the sodium channel.

Undesired effects

The conduction of electric impulses follows a similar mechanism in peripheral nerves, the central nervous system, and the heart. The effects of local anesthetics are therefore not specific for the signal conduction in peripheral nerves. Side effects on the central nervous system and the heart may be severe and potentially fatal. However, toxicity usually occurs only at nuclear plasma levels which are rarely reached if proper anesthetic techniques are adhered to. A diagram showing the CNS: 1. ... The heart and lungs, from an older edition of Grays Anatomy. ...

(See also local anesthetic toxicity) While generally safe, local anesthetic agents can be toxic if used in excessive doses or administered improperly. ...

Central nervous system

Depending on local tissue concentrations of local anesthetics, there may be excitatory or depressant effects on the central nervous system. At lower concentrations, a relatively selective depression of inhibitory neurons results in cerebral excitation, which may lead to generalized convulsions. A profound depression of brain functions occurs at 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 CSF, i.e. overdose in spinal anesthesia or accidental injection into the subarachnoid space in epidural anesthesia. This article is about the medical condition. ... For other uses, see Coma (disambiguation). ... Respiratory arrest is the cessation of the normal tidal flow of the lungs due to paralysis of the diaphragm, collapse of the lung or any number of respiratory failures. ... Spinal anaesthesia is a form of local, or more specifically regional, anaesthesia involving injection of a local anaesthetic into the cerebrospinal fluid (CSF), generally through a long fine needle. ... The meninges (singular meninx) are the system of membranes that contain the brain. ... The epidural space is a part of the human spine which is very close to the spinal cord, lying just outside the dura mater. ...

Cardiovascular system

The conductive system of the heart is quite sensitive to the action of local anesthetics. Lidocaine is often used as an antiarrhythmic drug and has been studied extensively, but the effects of other local anesthetics are probably similar to those of Lidocaine. Lidocaine acts by blocking sodium channels, leading to slowed conduction of impulses. This may obviously result in bradycardia, but tachyarrhythmia can also occur. With high plasma levels of lidocaine there may be higher-degree atrioventricular block and severe bradycardia, leading to coma and possibly death. Bradycardia, as applied to adult medicine, is defined as a resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. ... A cardiac arrhythmia, also called cardiac dysrhythmia, is a disturbance in the regular rhythm of the heartbeat. ...

Treatment of overdose: "Lipid rescue"

There is evidence that Intralipid, a commonly available intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anaesthetic overdose, including human case reports of successful use in this way ('lipid rescue').^{[1] [2][3][4][5]} Lipid Rescue is a term that has been coined to describe the use of intravenous lipid emulsion to treat severe local anaesthetic toxicity. ... An emulsion of fats that could be introduced into the body via a drip. ... Lipid Rescue is a term that has been coined to describe the use of intravenous lipid emulsion to treat severe local anaesthetic toxicity. ...

Hypersensitivity/Allergy

Adverse reactions to local anesthetics (especially the esters) are not uncommon, but true allergy is very rare. Allergic reactions to the esters is usually due to a sensitivity to their metabolite, para-aminobenzoic acid (PABA), and does not result in cross-allergy to amides. Therefore, amides can be used as alternatives in those patients. Non-allergic reactions may resemble allergy in their manifestations. In some cases, skin tests and provocative challenge may be necessary to establish a diagnosis of allergy. There are also cases of allergy to paraben derivatives, which are often added as preservatives to local anesthetic solutions. Allergy is an abnormal reaction to a substance foreign to the body that is acquired, predictable and rapid. ... Para-Aminobenzoic acid (PABA) is a chemical used in sunscreen that is an essential nutrient for some bacteria. ...

• Main Article: Allergic reactions during anaesthesia

The incidence of life-threatening hypersensitivity reactions occurring during anaesthesia is around one in 10,000 procedures. ...

Methemoglobinemia

The systemic toxicity of prilocaine is comparatively low, however its metabolite, o-toluidine, is known to cause methemoglobinemia. As methemoglobinemia reduces the amount of hemoglobin that is available for oxygen transport, this side effect is potentially life-threatening. Therefore dose limits for prilocaine should be strictly observed. Prilocaine is not recommended for use in infants. Prilocaine (IPA: ) is a local anesthetic of the amino amide type. ... Methemoglobinemia, also known as met-Hb, is a disorder characterized by the presence of a higher than normal level of methemoglobin in the blood. ... Structure of hemoglobin. ...

Local anesthetics in clinical use

• Amino esters
  • Benzocaine
  • Chloroprocaine
  • Cocaine
  • Procaine
  • Tetracaine/Amethocaine
• Amino amides
  • Bupivacaine
  • Levobupivacaine
  • Lidocaine/Lignocaine
  • Mepivacaine
  • Prilocaine
  • Ropivacaine
  • Articaine
  • Trimecaine

Esters are prone to producing allergic reactions, which may necessitate the use of an Amide. The names of Amides contain an "i" somewhere before the -aine. Esters do not. Benzocaine is a local anesthetic commonly used as a topical pain reliever. ... Chloroprocaine hydrochloride (Nesacaine®, Nesacaine-MPF®) is a local anesthetic given by injection during surgical procedures and labor and delivery. ... Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. ... Procaine is a local anesthetic drug of the amino ester group. ... Tetracaine (INN, also known as amethocaine; trade name Pontocaine) is a potent local anesthetic of amino ester group. ... Bupivacaine is a local anesthetic. ... Levobupivacaine (rINN) (IPA: ) is a local anaesthetic drug belonging to the amino amide group. ... Lidocaine (INN) (IPA: ) or lignocaine (former BAN) (IPA: ) is a common local anesthetic and antiarrhythmic drug. ... Lidocaine (INN) or lignocaine (former BAN) is a popular local anesthetic often used in dentistry or topically. ... Mepivacaine (IPA: ) is a local anesthetic of the amino amide type. ... Prilocaine (IPA: ) is a local anesthetic of the amino amide type. ... Ropivacaine (1-propyl-2’,6’-pipecoloxylidide; Naropin®) is a long-acting local anesthetic given by injection to reduce the sensation of pain. ... Septocaine® is a branded dental local anesthetic manufactured and distributed by Septodont. ...

• Combinations
  • Lidocaine/prilocaine (EMLA)

Lidocaine/prilocaine is a eutectic mixture of equal quantities (by weight) of lidocaine and prilocaine. ...

References

External links

• More on lipid rescue

See also

• Anesthetic
• General anaesthetic