Local anesthetic - AbsoluteAstronomy.com

A local anesthetic is a drug

Medication

A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

that causes reversible local anesthesia

Local anesthesia

Local anesthesia is any technique to induce the absence of sensation in part of the body, generally for the aim of inducing local analgesia, that is, local insensitivity to pain, although other local senses may be affected as well. It allows patients to undergo surgical and dental procedures with...

, generally for the aim of having local analgesic effect, that is, inducing absence of pain

Pain

Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

sensation, although other local senses are often affected as well. Also, when it is used on specific nerve pathways (nerve block

Nerve block

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 control of pain. It can also be used as a diagnostic tool to identify specific nerves as pain generators...

), paralysis

Paralysis

Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...

(loss of muscle

Muscle

Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

power) can be achieved as well.

Clinical local anesthetics belong to one of two classes: aminoamide and aminoester local anesthetics. Synthetic local anesthetics are structurally related to cocaine

Cocaine

Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

. 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

Hypertension

Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

or local vasoconstriction

Vasoconstriction

Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...

, with the exception of Ropivacaine

Ropivacaine

Ropivacaine is a local anaesthetic drug belonging to the amino amide group. The name ropivacaine refers to both the racemate and the marketed S-enantiomer...

and Mepivacaine

Mepivacaine

Mepivacaine is a local anesthetic of the amide type. Mepivacaine has a reasonably rapid onset and medium duration of action and is marketed under various trade names including Carbocaine and Polocaine.Mepivacaine became available in the United States in the 1960s.Mepivacaine is used in any...

that do produce weak vasoconstriction.

Local anesthetics vary in their pharmacological

Pharmacology

Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...

properties and they are used in various techniques of local anesthesia

Local anesthesia

such as:

Topical anesthesia
Topical anesthetic
A topical anesthetic is a local anesthetic that is used to numb the surface of a body part. They can be used to numb any area of the skin as well as the front of the eyeball, the inside of the nose, ear or throat, the anus and the genital area. Topical anesthetics are available in creams,...

(surface)
Infiltration
Infiltration (medical)
Infiltration is the diffusion or accumulation of substances not normal to it or in amounts in excess of the normal. The material collected in those tissues or cells is called infiltrate.-Classification:...
Plexus block
Epidural (extradural) block
Epidural
The term epidural is often short for epidural analgesia, a form of regional analgesia involving injection of drugs through a catheter placed into the epidural space...
Spinal anesthesia
Spinal anaesthesia
Spinal anaesthesia , also called spinal analgesia or sub-arachnoid block , is a form of regional anaesthesia involving injection of a local anaesthetic into the subarachnoid space, generally through a fine needle, usually 9 cm long...

(subarachnoid block)

The local anesthetic lidocaine

Lidocaine

Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...

(lignocaine) is also used as a Class Ib antiarrhythmic drug.

Mechanism of action

All local anesthetics 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 local anesthetics (propranolol, for example).
Local anesthetic drugs act mainly by inhibiting sodium

Sodium

Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

influx through sodium-specific ion channel

Ion channel

Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

s in the neuron

Neuron

A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

al cell membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

, in particular the so-called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential

Action potential

In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

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 inactivated state, 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

Base (chemistry)

For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...

and are usually formulated as the hydrochloride salt to render them water-soluble. At the chemical's pKa the protonated (ionized) and unprotonated (unionized) 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 (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 local anesthetic 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 anesthetic is ionized and therefore unable to cross the cell membrane to reach its cytoplasmic-facing site of action on the sodium channel.

All nerve fibers are sensitive to local anesthetics, but generally, those with a smaller diameter tend to be more sensitive than larger fibers. 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).
l./90[/-9

Acute pain

Acute pain may occur due to trauma, surgery, infection, disruption of blood circulation or many other conditions in which there is tissue injury. In a medical setting it is usually desirable to alleviate pain when its warning function is no longer needed. Besides improving patient comfort, pain therapy can also reduce harmful physiological consequences of untreated pain.

Acute pain can often be managed using analgesic

Analgesic

An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

s. However, conduction anesthesia may be preferable because of superior pain control and fewer side effects. For purposes of pain therapy, local anesthetic drugs are often given by repeated injection or continuous infusion through a catheter. Low doses of local anesthetic 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:

Labor pain (epidural anesthesia)
Postoperative pain (peripheral nerve blocks, epidural anesthesia)
Trauma (peripheral nerve blocks, intravenous regional anesthesia, epidural anesthesia)

Chronic pain

Chronic pain has several different meanings in medicine. Traditionally, the distinction between acute and chronic pain has relied upon an arbitrary interval of time from onset; the two most commonly used markers being 3 months and 6 months since the initiation of pain, though some theorists and...

of more than minor intensity is a complex and often serious condition that requires diagnosis and treatment by an expert in pain medicine. Local anesthetics can be applied repeatedly or continuously for prolonged periods to relieve chronic pain, usually in combination with medication such as opioid

Opioid

An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...

s, NSAIDs, and anticonvulsant

Anticonvulsant

The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...

Surgery and dentistry

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

Sedation

Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...

for the patient's comfort and ease of surgery. Typical operations performed under conduction anesthesia include:

Dentistry
Dentistry
Dentistry is the branch of medicine that is involved in the study, diagnosis, prevention, and treatment of diseases, disorders and conditions of the oral cavity, maxillofacial area and the adjacent and associated structures and their impact on the human body. Dentistry is widely considered...

(surface anesthesia, infiltration anesthesia or intraligamentary anesthesia during restorative operations or extractions, regional nerve blocks during extractions and surgeries.)
Eye surgery (surface anesthesia with topical anesthetic
Topical anesthetic
A topical anesthetic is a local anesthetic that is used to numb the surface of a body part. They can be used to numb any area of the skin as well as the front of the eyeball, the inside of the nose, ear or throat, the anus and the genital area. Topical anesthetics are available in creams,...

s, retrobulbar block
Retrobulbar block
A retrobulbar block is a regional anesthetic nerve block into the retrobulbar space, the area located behind the globe of the eye. Injection of local anesthetic into this space constitutes the retrobulbar block. This injection provides akinesia of the extraocular muscles by blocking cranial nerves...

)
ENT operations, head and neck surgery (infiltration anesthesia, field blocks, peripheral nerve blocks, plexus anesthesia)
Shoulder and arm surgery (plexus anesthesia, intravenous regional anesthesia
Intravenous regional anesthesia
Intravenous regional anesthesia or Bier block anesthesia is a common anesthetic technique for surgical procedures on the body's extremities where a local anesthetic is injected intravenously. The technique usually involves exsanguination, which forces blood out of the extremity, followed by the...

)
Heart and lung surgery (epidural anesthesia combined with general anesthesia)
Abdominal surgery (epidural/spinal anesthesia, often combined with general anesthesia)
Gynecological, obstetrical and urological operations (spinal/epidural anesthesia)
Bone and joint surgery of the pelvis, hip and leg (spinal/epidural anesthesia, peripheral nerve blocks, intravenous regional anesthesia
Intravenous regional anesthesia
Intravenous regional anesthesia or Bier block anesthesia is a common anesthetic technique for surgical procedures on the body's extremities where a local anesthetic is injected intravenously. The technique usually involves exsanguination, which forces blood out of the extremity, followed by the...

)
Surgery of skin and peripheral blood vessels (topical anesthesia, field blocks, peripheral nerve blocks, spinal/epidural anesthesia)

Other uses

Topical anesthesia, in the form of lidocaine/prilocaine

Lidocaine/prilocaine

Lidocaine/prilocaine is a eutectic mixture of equal quantities of lidocaine and prilocaine. A 5% emulsion preparation, containing 2.5% each of lidocaine/prilocaine, is marketed by APP Pharmaceuticals under the trade name EMLA .-Eutectic mixture:Separately, lidocaine and prilocaine are solid bases...

(EMLA) is most commonly used to enable relatively painless venipuncture

Venipuncture

In medicine, venepuncture, venopuncture or venipuncture is the process of obtaining intravenous access for the purpose of intravenous therapy or for blood sampling of venous blood. This procedure is performed by medical laboratory scientists, medical practitioners, some EMTs, paramedics,...

(blood

Blood

Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

collection) and placement of intravenous cannulae. It may also be suitable for other kinds of punctures such as ascites

Ascites

Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...

drainage and amniocentesis

Amniocentesis

Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for...

.

Surface anesthesia also facilitates some endoscopic

Endoscopy

Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...

procedures such as bronchoscopy

Bronchoscopy

Bronchoscopy is a technique of visualizing the inside of the airways for diagnostic and therapeutic purposes. An instrument is inserted into the airways, usually through the nose or mouth, or occasionally through a tracheostomy. This allows the practitioner to examine the patient's airways for...

(visualization of the lower airways) or cystoscopy

Cystoscopy

Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.Diagnostic cystoscopy is usually carried out with local anaesthesia...

(visualization of the inner surface of the bladder).

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 anestem merges into the central nervous system.

Injection of local anesthetics is often painful. A number of methods can be used to decrease this pain including buffering of the solution with bicarb and warming.

Clinical techniques include:

Surface anesthesia - application of local anesthetic 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 - injection of local anesthetic into the tissue to be anesthetized. Surface and infiltration anesthesia are collectively topical anesthesia.
Field block - subcutaneous injection of a local anesthetic in an area bordering on the field to be anesthetized.
Peripheral nerve block - injection of local anesthetic in the vicinity of a peripheral nerve to anesthetize that nerve's area of innervation.
Plexus anesthesia - injection of local anesthetic in the vicinity of a nerve plexus
Nerve plexus
A nerve plexus is a network of intersecting nerves. Except for the ventral rami of Th2-Th11 nerves, they combine sets of ventral rami of spinal nerves that serve the same area of the body into one large grouped nerve...

, 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 - a local anesthetic is injected into the epidural space
Epidural space
In the spine, the epidural space is the outermost part of the spinal canal. It is the space within the canal lying outside the dura mater...

where it acts primarily on the spinal nerve
Spinal nerve
The term spinal nerve generally refers to a mixed spinal nerve, which carries motor, sensory, and autonomic signals between the spinal cord and the body...

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 - a local anesthetic is injected into the cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

, usually at the lumbar spine (in the lower back), where it acts on spinal nerve
Spinal nerve
The term spinal nerve generally refers to a mixed spinal nerve, which carries motor, sensory, and autonomic signals between the spinal cord and the body...

roots and part of the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

. The resulting anesthesia usually extends from the legs to the abdomen or chest.
Intravenous regional anesthesia
Intravenous regional anesthesia
Intravenous regional anesthesia or Bier block anesthesia is a common anesthetic technique for surgical procedures on the body's extremities where a local anesthetic is injected intravenously. The technique usually involves exsanguination, which forces blood out of the extremity, followed by the...

(Bier's block) - blood circulation of a limb is interrupted using a tourniquet (a device similar to a blood pressure cuff), then a large volume of local anesthetic 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 (e.g. intrapleural anesthesia, intraarticular anesthesia)

Localized adverse effects

The local adverse effects of anesthetic agents include neurovascular manifestations such as prolonged anesthesia

Anesthesia

Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...

(numbness) and paresthesia

Paresthesia

Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...

(tingling, feeling of "pins and needles", or strange sensations). These are symptoms of localized nerve impairment or nerve damage

Nerve Damage

Nerve Damage is a compilation album by Groove Metal band Skinlab, released in 2004. It is a 2CD collection of rare and unreleased material, including a live set, demos, remixes, alternate mixes, and two new tracks.-Disc 1:# "Losing All" – 4:04...

Risks

The risk of temporary or permanent nerve damage varies between different locations and types of nerve block

Nerve block

Recovery

Permanent nerve damage after a peripheral nerve block

Nerve block

is rare. 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.

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

Causes

Causes of localized symptoms include:

neurotoxicity due to allergenic reaction,
excessive fluid pressure in a confined space,
severing of nerve fibers or support tissue with the needle/catheter,
injection-site hematoma
Hematoma
A hematoma, or haematoma, is a localized collection of blood outside the blood vessels, usually in liquid form within the tissue. This distinguishes it from an ecchymosis, which is the spread of blood under the skin in a thin layer, commonly called a bruise...

that puts pressure on the nerve, or
injection-site infection that produces inflammatory pressure on the nerve and/or necrosis.

General adverse effects

(See also local anesthetic toxicity

Local anesthetic toxicity

While generally safe, local anesthetic agents can be toxic if used in excessive doses or administered improperly. Even when administered properly, patients may still experience unintended reactions to local anesthetics....

)

General systemic adverse affects are due to the pharmacological effects of the anesthetic agents used. The conduction of electric impulses follows a similar mechanism in peripheral nerves, the central nervous system

Central nervous system

The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

, and the heart

Heart

The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

. 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 convulsion

Convulsion

A convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym for seizure...

s. A profound depression of brain functions occurs at higher concentrations which may lead to coma

Coma

In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...

, respiratory arrest

Respiratory arrest

Respiratory arrest is the cessation of breathing. It is a medical emergency and it usually is related to or coincides with a cardiac arrest. Causes include opiate overdose, head injury, anaesthesia, tetanus, or drowning...

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

Subarachnoid space

In the central nervous system, the subarachnoid cavity is the interval between the arachnoid membrane and pia mater....

in epidural anesthesia.

Cardiovascular system

The conductive system of the heart is quite sensitive to the action of local anesthetic

Treatment of overdose: "Lipid rescue"

There is evidence that Intralipid

Intralipid

Intralipid is a brand name for the first safe fat emulsion for human use, approved in 1962 in Europe and invented by Professor Arvid Wretlind, Sweden. The FDA initially would not approve the product due to prior experience with another fat emulsion. It was approved in the United States in 1972...

, a commonly available intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anesthetic overdose, including human case reports of successful use in this way ('lipid rescue').

Hypersensitivity/allergy

Adverse reactions to local anesthetics (especially the esters) are not uncommon, but true allergy

Allergy

An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...

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.

Stub: Allergic reactions during anesthesia
Allergic reactions during anaesthesia
The incidence of life-threatening hypersensitivity reactions occurring during surgery and anaesthesia is around one in 10,000 procedures. Serious allergic reactions to anesthetic medications are rare and a usually attributable to factors other than the anesthetic...

Methemoglobinemia

The systemic toxicity of prilocaine

Prilocaine

Prilocaine is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Lofgren. In its injectable form , it is often used in dentistry. It is also often combined with lidocaine as a preparation for dermal anesthesia , for treatment of conditions like paresthesia...

is comparatively low, however its metabolite, o-toluidine, is known to cause methemoglobinemia

Methemoglobinemia

Methemoglobinemia is a disorder characterized by the presence of a higher than normal level of methemoglobin in the blood. Methemoglobin is an oxidized form of hemoglobin that has an increased affinity for oxygen, resulting in a reduced ability to release oxygen to tissues. The oxygen–hemoglobin...

. As methemoglobinemia reduces the amount of hemoglobin

Hemoglobin

Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

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 labor pains or infants.

Local anesthetics in clinical use

Esters

Amino esters

Amino esters are a class of local anesthetics.-Structure:Structurally, local anesthetics consist of three molecular components:* a lipophilic part* an intermediate aliphatic chain* a hydrophilic part...

are prone to producing allergic reactions, which may necessitate the use of an Amide

Amide

In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...

. The names of each locally clinical anesthetic have the suffix "-caine".

Most ester local anesthetics are metabolized by pseudocholinesterases, while amide local anesthetics are metabolized in the liver. This can be a factor in choosing an agent in patients with liver failure.

Esters

Benzocaine
Benzocaine
Benzocaine is a local anesthetic commonly used as a topical pain reliever, or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments...
Chloroprocaine
Chloroprocaine
Chloroprocaine is a local anesthetic given by injection during surgical procedures and labor and delivery. Chloroprocaine constricts blood vessels resulting in reduced blood loss; this is in contrast to other local anesthetics e.g. lidocaine, which do not do such...
Cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
Cyclomethycaine
Cyclomethycaine
Cyclomethycaine is a local anesthetic....
Dimethocaine
Dimethocaine
Dimethocaine, also known as larocaine, is a local anesthetic with stimulant properties that some studies have shown to be half the potency of cocaine. Anecdotal user reports indicate little euphoria and only mild stimulating effects, with many users failing to perceive any recreational effects...

/Larocaine
Piperocaine
Piperocaine
Piperocaine is a local anesthetic drug developed in the 1920s and used as its hydrochloride salt for infiltration and nerve blocks.-External links:*...
Propoxycaine
Propoxycaine
Propoxycaine is a local anesthetic....
Procaine
Procaine
Procaine is a local anesthetic drug of the amino ester group. It is used primarily to reduce the pain of intramuscular injection of penicillin, and it was also used in dentistry. Owing to the ubiquity of the trade name Novocain, in some regions procaine is referred to generically as novocaine...

/Novocaine
Proparacaine
Tetracaine
Tetracaine
Tetracaine is a potent local anesthetic of the ester group...

/Amethocaine

Amides

Articaine
Bupivacaine
Bupivacaine
Bupivacaine is a local anaesthetic drug belonging to the amino amide group. AstraZeneca commonly markets it under various trade names, including Marcain, Marcaine, Sensorcaine and Vivacaine.-Indications:...
Cinchocaine
Cinchocaine
Cinchocaine is an amide local anesthetic. It is the active ingredient in some topical hemorrhoid creams such as Proctosedyl...

/Dibucaine
Etidocaine
Etidocaine
Etidocaine, marketed under the trade name Duranest, is a local anesthetic given by injection during surgical procedures and labor and delivery. Etidocaine has a long duration of activity, and the main disadvantage of using during dentistry is increased bleeding during surgery....
Levobupivacaine
Levobupivacaine
Levobupivacaine is a local anaesthetic drug belonging to the amino amide group. It is the S-enantiomer of bupivacaine. Levobupivacaine hydrochloride is commonly marketed by Abbott under the trade name Chirocaine.-Clinical use:...
Lidocaine
Lidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...

/Lignocaine
Mepivacaine
Mepivacaine
Mepivacaine is a local anesthetic of the amide type. Mepivacaine has a reasonably rapid onset and medium duration of action and is marketed under various trade names including Carbocaine and Polocaine.Mepivacaine became available in the United States in the 1960s.Mepivacaine is used in any...
Prilocaine
Prilocaine
Prilocaine is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Lofgren. In its injectable form , it is often used in dentistry. It is also often combined with lidocaine as a preparation for dermal anesthesia , for treatment of conditions like paresthesia...
Ropivacaine
Ropivacaine
Ropivacaine is a local anaesthetic drug belonging to the amino amide group. The name ropivacaine refers to both the racemate and the marketed S-enantiomer...
Trimecaine
Trimecaine
Trimecaine is an organic compound used as a local anesthetic and cardial antiarrhythmic. It is white crystalline powder readily soluble in water and ethanol...

Combinations

Local anesthetics mixed with other local anesthetics include:

Lidocaine/prilocaine
Lidocaine/prilocaine
Lidocaine/prilocaine is a eutectic mixture of equal quantities of lidocaine and prilocaine. A 5% emulsion preparation, containing 2.5% each of lidocaine/prilocaine, is marketed by APP Pharmaceuticals under the trade name EMLA .-Eutectic mixture:Separately, lidocaine and prilocaine are solid bases...

(EMLA)

Local anesthetics and vasoconstrictors
Vasoconstrictors 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. Examples include:

Prilocaine
Prilocaine
Prilocaine is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Lofgren. In its injectable form , it is often used in dentistry. It is also often combined with lidocaine as a preparation for dermal anesthesia , for treatment of conditions like paresthesia...

hydrochloride and epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

(trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....

Citanest Forte)

Naturally Derived Local Anesthetics

Saxitoxin
Saxitoxin
Saxitoxin is a neurotoxin naturally produced by certain species of marine dinoflagellates and cyanobacteria Saxitoxin (STX) is a neurotoxin naturally produced by certain species of marine dinoflagellates (Alexandrium sp., Gymnodinium sp., Pyrodinium sp.) and cyanobacteria Saxitoxin (STX) is a...
Tetrodotoxin
Tetrodotoxin
Tetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...
Menthol
Menthol
Menthol is an organic compound made synthetically or obtained from peppermint or other mint oils. It is a waxy, crystalline substance, clear or white in color, which is solid at room temperature and melts slightly above. The main form of menthol occurring in nature is -menthol, which is assigned...
Eugenol
Eugenol
Eugenol is a phenylpropene, an allyl chain-substituted guaiacol. Eugenol is a member of the phenylpropanoids class of chemical compounds. It is a clear to pale yellow oily liquid extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, basil and bay leaf. It is slightly...

Naturally occurring local anesthetics not derived from cocaine are usually neurotoxin

Neurotoxin

A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...

s, and have the suffix -toxin in their names. http://books.google.com/books?id=jvema9PNEPgC&pg=RA1-PA43&lpg=RA1-PA43&dq=%22natural+local+anesthetics%22&source=web&ots=OLV_2SsTwp&sig=IijVsDKoHaXldm33ySEsav8hPvI Unlike cocaine produced local anesthetics which are intracellular

Intracellular

Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...

in effect, saxitoxin & tetrodotoxin bind to the extracellular

Extracellular

In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...

side of sodium channels.

History

The leaves of the coca plant

Coca

Coca, Erythroxylum coca, is a plant in the family Erythroxylaceae, native to western South America. The plant plays a significant role in many traditional Andean cultures...

were traditionally used as a stimulant in Peru

Peru

Peru , officially the Republic of Peru , is a country in western South America. It is bordered on the north by Ecuador and Colombia, on the east by Brazil, on the southeast by Bolivia, on the south by Chile, and on the west by the Pacific Ocean....

. It is believed that the local anesthetic effect of coca was also known and used for medical purposes. Cocaine

Cocaine

was isolated in 1860 and first used as a local anesthetic in 1884. The search for a less toxic and less addictive substitute led to the development of the aminoester local anesthetic procaine

Procaine

Procaine is a local anesthetic drug of the amino ester group. It is used primarily to reduce the pain of intramuscular injection of penicillin, and it was also used in dentistry. Owing to the ubiquity of the trade name Novocain, in some regions procaine is referred to generically as novocaine...

in 1904. Since then, several synthetic local anesthetic drugs have been developed and put into clinical use, notably lidocaine

Lidocaine

in 1943, bupivacaine

Bupivacaine

Bupivacaine is a local anaesthetic drug belonging to the amino amide group. AstraZeneca commonly markets it under various trade names, including Marcain, Marcaine, Sensorcaine and Vivacaine.-Indications:...

in 1957 and prilocaine

Prilocaine

in 1959.

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

August Bier

August Karl Gustav Bier was a German surgeon and a pioneer of spinal anaesthesia. After professorships in Greifswald and Bonn, Bier became a professor at the Charité in Berlin.-Spinal anesthesia:...

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 (non-cutting-tip) cannulas 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

Fidel Pagés

Fidel Pagés Miravé was a Spanish military surgeon, known for developing the technique of epidural anesthesia....

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 a highly successful technique to this day. Beside its many uses for surgery, epidural anesthesia is particularly popular in obstetrics for the treatment of labor pain.