A local anesthetic is a drug that causes reversible local anesthesia and a loss of nociception. Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease Local anesthesia is any technique to render part of the body insensitive to pain without affecting consciousness Nociception (synonym nociperception is defined as "the neural processes of encoding and processing Noxious stimuli. When it is used on specific nerve pathways (nerve block), effects such as analgesia (loss of pain sensation) and paralysis (loss of muscle power) can be achieved. Regional nerve blockade, or more commonly nerve block, is a general term used to refer to the injection of Local anesthetic onto or near Nerves for temporary Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm Paralysed redirects here For other uses see xx Paralysed (disambiguation Paralysis is the complete loss of Muscle function Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the

Clinical local anesthetics belong to one of two classes: aminoamide and aminoester local anesthetics. Synthetic local anesthetics are structurally related to cocaine. Cocaine ( benzoylmethyl ecgonine) is a Crystalline Tropane Alkaloid that is obtained from the leaves of the Coca plant 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. Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels particularly the large Arteries, Arterioles Ropivacaine ( rINN) (roʊˈpɪvəkeɪn is a Local anaesthetic drug belonging to the Amino Amide group Mepivacaine (mɛˈpɪvəkeɪn 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:

• 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. Pharmacology (from Greek grc φάρμακον pharmakon, "drug" and grc -λογία -logia) is the study of how Drugs Local anesthesia is any technique to render part of the body insensitive to pain without affecting consciousness A topical anesthetic is a Local anesthetic that is used to numb the surface of a body part Infiltration is the Diffusion or Accumulation (in a tissue or cells of Substances not normal to it or in amounts in Excess Lidocaine ( INN) (ˈlaɪdoʊkeɪn or lignocaine (former BAN) (/ˈlɪgnoʊkeɪn/ 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

Contents 1 Mechanism of action 2 Undesired Effects 2.1 Localized Adverse Effects 2.1.1 Risks 2.1.2 Recovery 2.1.3 Causes 2.2 General Adverse Effects 2.2.1 Central nervous system 2.2.2 Cardiovascular system 2.2.3 Treatment of overdose: "Lipid rescue" 2.2.4 Hypersensitivity/Allergy 2.2.5 Methemoglobinemia 3 Local anesthetics in clinical use 4 Natural local anesthetics 5 See also 6 Footnotes 7 References

Mechanism of action

All local anesthetics are membrane stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes (like neurons). The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Though many other drugs also have membrane stabilizing properties, all are not used as local anesthetics, for example propranolol. Propranolol ( INN) is a non-selective Beta blocker mainly used in the treatment of Hypertension. 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. Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 Ion channels are pore-forming Proteins that help establish and control the small Voltage Gradient across the Plasma membrane of all living Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. In Neurophysiology, the action potential is a self-regenerating Wave of Electrochemical activity that allows Nerve cells to carry a signal 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.

Local anesthetics are weak bases and are usually formulated as the hydrochloride salt to render them water-soluble. In Chemistry, a base is most commonly thought of as an aqueous substance that can accept Protons This refers to the Brønsted-Lowry theory of acids and 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.

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.

All nerve fibres are sensitive to local anesthetics, but generally, those with a smaller diameter tend to be more sensitive than larger fibres. Local anesthetics block conduction in the following order: small myelinated axons (e. g. those carrying nociceptive impulses), non-myelinated axons, then large myelinated axons. Thus, a differential block can be achieved (i. e. pain sensation is blocked more readily than other sensory modalities).

Undesired Effects

Localized Adverse Effects

The local adverse effects of anesthetic agents include neurovascular manifestations such as prolonged anesthesia (numbness) and paresthesia (tingling, feeling of "pins and needles", or strange sensations). Anesthesia, or anaesthesia (see spelling differences; from Greek grc αν- an-, "without" and grc αἲσθησις Paresthesia (pron /ˌpɛɹɪsˈθiʒə/ paraesthesia in British English, pron These are symptoms of localized nerve impairment or nerve damage. There is no single classification system that can describe all the many variations of nerve injury.

Risks

The risk of temporary or permanent nerve damage varies between different locations and types of nerve blocks ^[1]. Regional nerve blockade, or more commonly nerve block, is a general term used to refer to the injection of Local anesthetic onto or near Nerves for temporary

Recovery

Permanent nerve damage after a peripheral nerve block is rare. Regional nerve blockade, or more commonly nerve block, is a general term used to refer to the injection of Local anesthetic onto or near Nerves for temporary Symptoms are very likely to resolve within a few weeks. The vast majority of those affected (92–97%), recover within four to six weeks. 99% of these people have recovered within a year. It is estimated that between 1 in 5,000 and 1 in 30,000 nerve blocks result in some degree of permanent persistent nerve damage ^[2].

It is suggested that symptoms may continue to improve for up to 18 months following injury.

Causes

Causes of localized symptoms include:

1. neurotoxicity due to allergenic reaction,
2. excessive fluid pressure in a confined space,
3. severing of nerve fibers or support tissue with the syringe/catheter,
4. injection-site [Hematoma] that puts pressure on the nerve, or
5. injection-site infection that produces inflammatory pressure on the nerve and/or necrosis.

General Adverse Effects

(See also local anesthetic toxicity)

General systemic adverse affects are due to the pharmacological effects of the anesthetic agents used. While generally safe Local anesthetic agents can be toxic if used in excessive doses or administered improperly The conduction of electric impulses follows a similar mechanism in peripheral nerves, the central nervous system, and the heart. In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic 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 plasma levels which are rarely reached if proper anesthetic techniques are adhered to. Additionally, persons may exhibit allergenic reactions to the anesthetic compounds and may also exhibit cyanosis due to methemoglobinemia.

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. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting A profound depression of brain functions occurs at higher concentrations which may lead to coma, respiratory arrest and death. In Medicine, a coma (from the Greek koma, meaning deep sleep is a profound state of Unconsciousness. Respiratory arrest is the cessation of Breathing. It is a Medical emergency and it usually is related to or coincides with a Cardiac arrest. 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. Spinal analgesia, (or commonly called spinal anesthesia or sub-arachnoid block (S In the Central nervous system, the subarachnoid cavity ( subarachnoid space) is the interval between the Arachnoid membrane and Pia mater The term epidural is often short for epidural anesthesia, a form of Regional anesthesia involving injection of drugs through a Catheter placed into the

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. 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 Dysrhythmia redirects here For the American band see Dysrhythmia (band. With high plasma levels of lidocaine there may be higher-degree atrioventricular block and severe bradycardia, leading to coma and possibly death.

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'). Intralipid is a brand name for the first safe fat emulsion for human use approved in 1962 and invented by Professor Arvid Wretlind Sweden Lipid Rescue is a term that has been coined to describe the use of intravenous lipid emulsion to treat severe Local anaesthetic toxicity ^{[3] [4][5][6][7]}

Hypersensitivity/Allergy

Adverse reactions to local anesthetics (especially the esters) are not uncommon, but true allergy is very rare. Allergy is a disorder of the Immune system often also referred to as Atopy. 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. 4-Aminobenzoic acid (also known as para -aminobenzoic acid or PABA) is an Organic compound with the molecular formula C7H7NO2 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.

• Stub: Allergic reactions during anaesthesia

Methemoglobinemia

The systemic toxicity of prilocaine is comparatively low, however its metabolite, o-toluidine, is known to cause methemoglobinemia. The incidence of life-threatening Hypersensitivity reactions occurring during Anaesthesia is around one in 10000 procedures Prilocaine (ˈpraɪloʊkeɪn is a Local anesthetic of the Amino Amide type Methemoglobinemia is a disorder characterized by the presence of a higher than normal level of Methemoglobin (metHb in the Blood. As methemoglobinemia reduces the amount of hemoglobin that is available for oxygen transport, this side effect is potentially life-threatening. Hemoglobin ( also spelled haemoglobin and abbreviated Hb or Hgb) is the Iron -containing Oxygen -transport Metalloprotein Therefore dose limits for prilocaine should be strictly observed. Prilocaine is not recommended for use in infants.

Local anesthetics in clinical use

• Amino esters
  • Benzocaine
  • Chloroprocaine
  • Cocaine
  • Cyclomethycaine
  • Dimethocaine/Larocaine
  • Propoxycaine
  • Procaine/Novocaine
  • Proparacaine
  • Tetracaine/Amethocaine
• Amino amides
  • Articaine
  • Bupivacaine
  • Carticaine
  • Cinchocaine/Dibucaine
  • Etidocaine
  • Levobupivacaine
  • Lidocaine/Lignocaine
  • Mepivacaine
  • Piperocaine
  • Prilocaine
  • Ropivacaine
  • Trimecaine

Esters are prone to producing allergic reactions, which may necessitate the use of an Amide. Structurally local Anesthetics consist of three molecular components a Lipophilic part an intermediate Aliphatic chain Benzocaine is a Local anesthetic commonly used as a Topical pain reliever Chloroprocaine hydrochloride (trade name Nesacaine, Nesacaine-MPF) is a Local anesthetic given by injection during surgical procedures Cocaine ( benzoylmethyl ecgonine) is a Crystalline Tropane Alkaloid that is obtained from the leaves of the Coca plant Dimethocaine, also known as larocaine, is a Local anesthetic with Stimulant properties nearly as potent as Cocaine. Dimethocaine, also known as larocaine, is a Local anesthetic with Stimulant properties nearly as potent as Cocaine. Procaine is a Local anesthetic drug of the Amino Ester group It is used primarily to reduce the pain of Intramuscular injection of Procaine is a Local anesthetic drug of the Amino Ester group It is used primarily to reduce the pain of Intramuscular injection of Proparacaine (Alcaine Ak-Taine is a Topical anesthetic drug of the amino ester group Tetracaine ( INN, also known as amethocaine; trade name Pontocaine) is a potent Local anesthetic of the Ester group Tetracaine ( INN, also known as amethocaine; trade name Pontocaine) is a potent Local anesthetic of the Ester group Articaine is a dental local anesthetic It is manufactured and distributed by Septodont under the brand name Septocaine and under the name of Ultracaine by Sanofi-Aventis Bupivacaine ( rINN) (bjuːˈpɪvəkeɪn is a Local anaesthetic drug belonging to the Amino Amide group Cinchocaine (or Dibucaine) is an Amide Local anesthetic. It is the active ingredient in some topical hemorrhoid creams Cinchocaine (or Dibucaine) is an Amide Local anesthetic. It is the active ingredient in some topical hemorrhoid creams Etidocaine, marketed under the trade name Duranest, is a Local anesthetic given by injection during surgical procedures and labor and delivery Levobupivacaine ( rINN) (liːvoʊbjuːˈpɪvəkeɪn is a Local anaesthetic drug belonging to the Amino Amide group Lidocaine ( INN) (ˈlaɪdoʊkeɪn or lignocaine (former BAN) (/ˈlɪgnoʊkeɪn/ is a common Local anesthetic and antiarrhythmic drug Lidocaine ( INN) (ˈlaɪdoʊkeɪn or lignocaine (former BAN) (/ˈlɪgnoʊkeɪn/ is a common Local anesthetic and antiarrhythmic drug Mepivacaine (mɛˈpɪvəkeɪn is a Local anesthetic of the Amino Amide type Piperocaine is a Local anesthetic drug used as its Hydrochloride salt for infiltration and Nerve blocks Prilocaine (ˈpraɪloʊkeɪn is a Local anesthetic of the Amino Amide type Ropivacaine ( rINN) (roʊˈpɪvəkeɪn is a Local anaesthetic drug belonging to the Amino Amide group The names of Amides contain an "i" somewhere before the -aine. Esters do not.

• Combinations
  • Lidocaine/prilocaine (EMLA)

Natural local anesthetics

• Saxitoxin
• Tetrodotoxin

Naturally occurring local anesthetics not derived from cocaine are usually neurotoxins, and have the suffix -toxin in their names. Lidocaine/prilocaine is a eutectic mixture of equal quantities (by weight of Lidocaine and Prilocaine. Saxitoxin ( STX) is a neurotoxin naturally produced by certain species of marine Dinoflagellates ( Alexandrium sp Tetrodotoxin (anhydrotetrodotoxin 4-epitetrodotoxin tetrodonic acid TTX is a potent Neurotoxin with no known antidote which blocks Action potentials in Nerves A neurotoxin is a Toxin that acts specifically on nerve cells ( Neurons, usually by interacting with Membrane proteins such as Ion channels [1] Unlike cocaine produced local anesthetics which are intracellular in effect, saxitoxin & tetrodotoxin bind to the extracellular side of sodium channels. Not to be confused with Intercellular, meaning "between cells" In Cell biology, Molecular biology and related fields the word extracellular (or sometimes extracellular space) means "outside the cell

See also

• Anesthetic
• General anaesthetic
• List of cocaine analogues

Footnotes

References

“Nerve damage associated with peripheral nerve block”, Risks associated with your anaesthetic, (The Royal College of Anaesthetists) Section 12, January 2006, <http://www.rcoa.ac.uk/docs/nerve-peripheral.pdf>. Retrieved on 10 October 2007 

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