![Local anesthetics general structure](https://upload.wikimedia.org/wikipedia/commons/f/fd/Local_anesthetics_general_structure.svg)
A local anesthetic (LA) is a
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
that causes absence of
pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a
general anesthetic
General anaesthetics (or anesthetics, see spelling differences) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma ...
. When it is used on specific nerve pathways (
local anesthetic nerve block
Local anesthetic nerve block (local anesthetic regional nerve blockade, or often simply nerve block) is a short-term nerve block involving the injection (medicine), injection of local anesthetic as close to the nerve as possible for analgesia, pai ...
),
paralysis
Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...
(loss of
muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
power) also can be achieved.
Examples
Short Duration & Low Potency
Procaine
Procaine is a local anesthetic drug of the amino ester group. It is most commonly used in dental procedures to numb the area around a tooth and is also used to reduce the pain of intramuscular injection of penicillin. Owing to the ubiquity ...
Chloroprocaine
Chloroprocaine (trade name Nesacaine, Nesacaine-MPF) (often in the hydrochloride salt form as the aforementioned trade names) is a local anesthetic given by injection during surgical procedures and labor and delivery. Chloroprocaine vasodilates; t ...
Medium Duration & Potency
Lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
Prilocaine
Prilocaine () is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Löfgren. In its injectable form (trade name Citanest), it is often used in dentistry. It is also often combined with lidocaine as a topical p ...
High Duration & Potency
Tetracaine
Tetracaine, also known as amethocaine, is an ester local anesthetic used to numb the eyes, nose, or throat. It may also be applied to the skin before starting an intravenous (injection) to decrease pain from the procedure. Typically it is applied ...
Bupivacaine
Cinchocaine
Cinchocaine (INN/ BAN) or dibucaine (USAN) is an amide local anesthetic. Among the most potent and toxic of the long-acting local anesthetics, current use of cinchocaine is generally restricted to spinal and topical anesthesia. It is sold under th ...
Ropivacaine
Ropivacaine (rINN) is a local anaesthetic drug belonging to the amino amide group. The name ropivacaine refers to both the racemate and the marketed ''S''-enantiomer. Ropivacaine hydrochloride is commonly marketed by AstraZeneca under the brand na ...
Clinical LAs belong to one of two classes: aminoamide and aminoester local anesthetics. Synthetic LAs are structurally related to
cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
. They differ from cocaine mainly in that they have a very low abuse potential and do not produce
hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
or (with few exceptions)
vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessel ...
.
They are used in various techniques of
local anesthesia
Local anesthesia is any technique to induce the absence of sensation in a specific 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 ...
such as:
*
Topical anesthesia 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. Topi ...
(surface)
* Topical administration of cream, gel, ointment, liquid, or spray of anaesthetic dissolved in
DMSO or other solvents/carriers for deeper absorption
*
Infiltration
Infiltration may refer to:
Science, medicine, and engineering
*Infiltration (hydrology), downward movement of water into soil
*Infiltration (HVAC), a heating, ventilation, and air conditioning term for air leakage into buildings
*Infiltration (me ...
*
Brachial plexus block
*
Epidural (extradural) block
*
Spinal anesthesia
Spinal anaesthesia (or spinal anesthesia), also called spinal block, subarachnoid block, intradural block and intrathecal block, is a form of neuraxial regional anaesthesia involving the injection of a local anaesthetic or opioid into the subarac ...
(subarachnoid block)
*
Iontophoresis
Iontophoresis is a process of transdermal drug delivery by use of a voltage gradient on the skin. Molecules are transported across the stratum corneum by electrophoresis and electroosmosis and the electric field can also increase the permeability ...
The suffix "-caine" at the ends of these medication names was extracted from the word "
cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
", because cocaine was formerly used as a local anesthetic.
Medical uses
Acute pain
Acute pain may occur due to trauma, surgery, infection, disruption of blood circulation, or many other conditions in which tissue injury occurs. In a medical setting, pain alleviation is desired 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
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
s. However, 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:
* Labor pain (epidural anesthesia, pudendal nerve blocks)
* Postoperative pain (peripheral nerve blocks, epidural anesthesia)
* Trauma (peripheral nerve blocks, intravenous regional anesthesia, epidural anesthesia)
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
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
s,
NSAID
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s, and
anticonvulsant
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
s. Though it can be easily performed, repeated local anaesthetic 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
General anaesthesia (UK) or general anesthesia (US) is a medically induced loss of consciousness that renders the patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general ...
or
sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...
for the patient's comfort and ease of surgery. However, many anaesthetists, 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:
*
Dentistry
Dentistry, also known as dental medicine and oral medicine, is the branch of medicine focused on the teeth, gums, and mouth. It consists of the study, diagnosis, prevention, management, and treatment of diseases, disorders, and conditions o ...
(surface anesthesia, infiltration anesthesia or intraligamentary anesthesia during restorative operations such as fillings, crowns, and root canals,
or extractions, and regional nerve blocks during extractions and surgeries)
*
Podiatry
Podiatry () or podiatric medicine () is a branch of medicine devoted to the study, diagnosis, medical and surgical treatment of disorders of the foot, ankle, and leg.
A Doctor of Podiatric Medicine (DPM), or a podiatrist, is a healthcare p ...
(cutaneous, nail avulsions, matricectomy, bunionectomy, hammertoe repair
and various other podiatric procedures)
*
Eye surgery
Eye surgery, also known as ophthalmic or ocular surgery, is surgery performed on the eye or its adnexa, by an ophthalmologist or sometimes, an optometrist. Eye surgery is synonymous with ophthalmology. The eye is a very fragile organ, and requ ...
(surface anesthesia with
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. Top ...
s or
retrobulbar block
A retrobulbar block is a regional anesthetic nerve block in 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 o ...
during cataract removal or other ophthalmic procedures
)
* ENT operations,
head and neck surgery
Otorhinolaryngology ( , abbreviated ORL and also known as otolaryngology, otolaryngology–head and neck surgery (ORL–H&N or OHNS), or ear, nose, and throat (ENT)) is a surgical subspeciality within medicine that deals with the surgical a ...
(infiltration anesthesia, field blocks, or peripheral nerve blocks, plexus anesthesia)
* Shoulder and arm surgery (plexus anesthesia or
intravenous regional anesthesia
Intravenous regional anesthesia (IVRA) or Bier's block anesthesia is an anesthetic technique on the body's extremities where a local anesthetic is injected intravenously and isolated from circulation in a target area. The technique usually involv ...
)
* Heart and lung surgery (
epidural anesthesia
Epidural administration (from Ancient Greek ἐπί, , upon" + ''dura mater'') is a method of medication administration in which a medicine is injected into the epidural space around the spinal cord. The epidural route is used by physicians and ...
combined with general anesthesia)
*
Abdominal surgery
The term abdominal surgery broadly covers Surgery, surgical procedures that involve opening the abdomen (laparotomy). Surgery of each abdominal organ is dealt with separately in connection with the description of that organ (see stomach, kidney, l ...
(epidural anesthesia/
spinal anesthesia
Spinal anaesthesia (or spinal anesthesia), also called spinal block, subarachnoid block, intradural block and intrathecal block, is a form of neuraxial regional anaesthesia involving the injection of a local anaesthetic or opioid into the subarac ...
, often combined with general anesthesia during inguinal hernia repair or other abdominal surgery
)
* Gynecological, obstetrical, and urological operations (spinal/epidural anesthesia)
* Bone and joint surgery of the
pelvis
The pelvis (plural pelves or pelvises) is the lower part of the trunk, between the abdomen and the thighs (sometimes also called pelvic region), together with its embedded skeleton (sometimes also called bony pelvis, or pelvic skeleton).
The ...
,
hip
In vertebrate anatomy, hip (or "coxa"Latin ''coxa'' was used by Celsus in the sense "hip", but by Pliny the Elder in the sense "hip bone" (Diab, p 77) in medical terminology) refers to either an anatomical region or a joint.
The hip region is ...
, and
leg
A leg is a weight-bearing and animal locomotion, locomotive anatomical structure, usually having a columnar shape. During locomotion, legs function as "extensible struts". The combination of movements at all joints can be modeled as a single ...
(spinal/epidural anesthesia, peripheral nerve blocks, or intravenous regional anesthesia)
* Surgery of skin and peripheral blood vessels (
topical anesthesia 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. Topi ...
, field blocks, peripheral nerve blocks, or spinal/epidural anesthesia)
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
Lidocaine/prilocaine is a eutectic mixture of equal quantities (by weight) 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 (an ...
(EMLA) is most commonly used to enable relatively painless
venipuncture
In medicine, venipuncture or venepuncture is the process of obtaining intravenous access for the purpose of venous blood sampling (also called ''phlebotomy'') or intravenous therapy. In healthcare, this procedure is performed by medical labo ...
(
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
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
An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are insert ...
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 anaesthesia. 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-sterilisation 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 anaesthetic 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 2 hours.
The side effects of inferior alveolar nerve block include feeling tense, clenching of the fists and moaning.
The duration of soft tissue anaesthesia is longer than pulpal anaesthesia and is often associated with difficulty eating, drinking and speaking.
Risks
The risk of temporary or permanent nerve damage varies between different locations and types of
nerve block
Nerve block or regional nerve blockade is any deliberate interruption of signals traveling along a nerve, often for the purpose of pain relief. Local anesthetic nerve block (sometimes referred to as simply "nerve block") is a short-term block, u ...
s.
There is risk of accidental damage to local blood vessels during injection of the local anaesthetic solution. This is referred to as Haematoma and could result in pain, trismus, swelling and/or discolouration of the region. The density of tissues surrounding the injured vessels is an important factor for Haematoma. There is greatest chance of this occurring in a posterior superior alveolar nerve block or in a pterygomandibular block.
Giving local anaesthesia 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 anaesthetic agents may be drastically increased thus increasing the risk of overdose.
Local anaesthetics 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 administrating any type of local anaesthetic to a pregnant patient.
Recovery
Permanent nerve damage after a peripheral nerve block is rare. Symptoms are 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. An estimated one in 5,000 to 30,000 nerve blocks results in some degree of permanent persistent nerve damage.
Symptoms may continue to improve for up to 18 months following injury.
Potential side effects
General systemic adverse effects are due to the pharmacological effects of the anesthetic agents used. The conduction of electric impulses follows a similar mechanism in
peripheral nerves
The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain a ...
, the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
, and the
heart
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
. 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. High plasma levels might arise, for example, when doses intended for
epidural or intrasupport tissue administration are accidentally delivered as
intravascular
The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...
injection.
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
The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of ...
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.
On the other hand, fear of administration can also result in accelerated, shallow breathing, or
hyperventilation
Hyperventilation is irregular breathing that occurs when the rate or tidal volume of breathing eliminates more carbon dioxide than the body can produce. This leads to hypocapnia, a reduced concentration of carbon dioxide dissolved in the blood. ...
. The patient may feel a tingling sensation in hands and feet or a sense of light-headedness and increased chest pressure.
Hence, it is crucial for the medical professional administrating the local anaesthesia, especially in the form of an injection, to ensure that the patient is in a comfortable setting and has any potential fears alleviated in order to avoid these possible complications.
Central nervous system
Depending on local tissue concentrations of local anesthetics, excitatory or depressant effects on the central nervous system may occur.
Initial symptoms of systemic toxicity include ringing in the ears (
tinnitus
Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...
), a metallic taste in the mouth, tingling or numbness of the mouth, dizziness and/or disorientation.
At higher concentrations, a relatively selective depression of inhibitory neurons results in cerebral excitation, which may lead to more advanced symptoms include motor twitching in the periphery followed by
grand mal seizures
Grand may refer to:
People with the name
* Grand (surname)
* Grand L. Bush (born 1955), American actor
* Grand Mixer DXT, American turntablist
* Grand Puba (born 1966), American rapper
Places
* Grand, Oklahoma
* Grand, Vosges, village and commu ...
. It is reported that seizures are more likely to occur when bupivacaine is used, particularly in combination with chloroprocaine.
A profound depression of brain functions may occur at even higher concentrations which may lead to
coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
,
respiratory arrest
Respiratory arrest is a sickness caused by apnea (cessation of breathing) or respiratory dysfunction severe enough it will not sustain the body (such as agonal breathing). Prolonged apnea refers to a patient who has stopped breathing for a long p ...
, 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
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
, 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.
This may affect the nervous system or cause the agent to enter into general circulation. However, infections are very seldom transmitted.
Cardiac toxicity associated with overdose of intravascular injection of local anesthetic is characterized by
hypotension
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...
,
atrioventricular conduction delay,
idioventricular rhythms, and eventual cardiovascular collapse. Although all local anesthetics potentially shorten the myocardial refractory period,
bupivacaine blocks the cardiac sodium channels, thereby making it most likely to precipitate malignant
arrhythmias. Even
levobupivacaine
Levobupivacaine (International Nonproprietary Name, rINN) is a local anaesthetic drug belonging to the amino amide group. It is the ''S''-enantiomer of bupivacaine.
Levobupivacaine hydrochloride is commonly marketed by AbbVie under the trade nam ...
and
ropivacaine
Ropivacaine (rINN) is a local anaesthetic drug belonging to the amino amide group. The name ropivacaine refers to both the racemate and the marketed ''S''-enantiomer. Ropivacaine hydrochloride is commonly marketed by AstraZeneca under the brand na ...
(single-enantiomer derivatives), developed to ameliorate cardiovascular side effects, still harbor the potential to disrupt cardiac function. Toxicity from anesthetic combinations is additive.
Endocrine
Endocrine and metabolic systems only have slightly adverse effects with most cases being without clinical repercussions.
Immunologic allergy
Adverse reactions to local anesthetics (especially the esters) are not uncommon, but legitimate
allergies are very rare. Allergic reactions to the esters is usually due to a sensitivity to their metabolite,
para-aminobenzoic acid
4-Aminobenzoic acid (also known as ''para''-aminobenzoic acid or PABA because the two functional groups are attached to the benzene ring across from one another in the ''para'' position) is an organic compound with the formula H2NC6H4CO2H. PABA i ...
, and does not result in cross-allergy to amides.
[Univ. of Wisconsin, Local Anesthesia and Regional Anesthetics] 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
Parabens are a class of widely used preservatives in cosmetic and pharmaceutical products. Chemically, they are a series of parahydroxybenzoates or esters of parahydroxybenzoic acid (also known as 4-hydroxybenzoic acid). Parabens are effective p ...
derivatives occur, which are often added as preservatives to local anesthetic solutions.
Methemoglobinemia
Methemoglobinemia
Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated methemoglobin in the blood. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis). Complications m ...
is a process where iron in hemoglobin is altered, reducing its oxygen-carrying capability, which produces
cyanosis
Cyanosis is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that show cyanosis are usually in locations ...
and symptoms of
hypoxia
Hypoxia means a lower than normal level of oxygen, and may refer to:
Reduced or insufficient oxygen
* Hypoxia (environmental), abnormally low oxygen content of the specific environment
* Hypoxia (medical), abnormally low level of oxygen in the tis ...
. Exposure to aniline group chemicals such as
benzocaine
Benzocaine, sold under the brand name Orajel amongst others, is an ester 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 such as products f ...
,
lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
, and
prilocaine
Prilocaine () is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Löfgren. In its injectable form (trade name Citanest), it is often used in dentistry. It is also often combined with lidocaine as a topical p ...
can produce this effect, especially benzocaine.
The systemic toxicity of prilocaine is comparatively low, but its metabolite, o-toluidine, is known to cause
methemoglobinemia
Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated methemoglobin in the blood. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis). Complications m ...
.
Second-generation effects
Application of local anesthetics during oocyte removal during in vitro fertilisation has been up to debate. Pharmacological concentrations of anesthetic agents have been found in follicular fluid.
Clinical trials have not concluded any effects on pregnant women. However, there is some concern with the behavioral effects of lidocaine on offspring in rats.
During pregnancy, it is not common for local anesthetics to have any adverse effect on the fetus. Despite this, risks of toxicity may be higher in pregnancy due to an increase in unbound fraction of local anesthetic and physiological changes increase the transfer of local anesthetic into the central nervous system.
Hence, it is recommended that pregnant women use a lower dose of local anesthetic to reduce any potential complications.
Treatment of overdose: "Lipid rescue"
This method of toxicity treatment was invented by Dr. Guy Weinberg in 1998, and was not widely used until after the first published successful rescue in 2006. Evidence indicates
Intralipid
Lipid emulsion or fat emulsion refers to an emulsion of lipid for human intravenous use, especially catering critically-ill patients that cannot consume food and administer their required nutrients enterally. It is often referred to by the brand na ...
, 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
A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general an ...
).
However, the evidence at this point is still limited.
Though most reports to date have used Intralipid, a commonly available intravenous lipid emulsion, other emulsions, such as Liposyn and Medialipid, have also been shown effective.
Ample supporting animal evidence
and human case reports show successful use in this way.
In the UK, efforts have been made to publicise this use more widely
and lipid rescue has now been officially promoted as a treatment by the
Association of Anaesthetists of Great Britain and Ireland
The Association of Anaesthetists, in full the Association of Anaesthetists of Great Britain and Ireland (AAGBI), is a professional association for anaesthetists in the United Kingdom and Ireland.
It was founded by Dr Henry Featherstone in 193 ...
. One published case has been reported of successful treatment of refractory
cardiac arrest
Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
in
bupropion
Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the case ...
and
lamotrigine
Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut synd ...
overdose using lipid emulsion.
The design of a 'homemade' lipid rescue kit 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
Moxidectin is an anthelmintic drug used in animals to prevent or control parasitic worms (helminths), such as heartworm and intestinal worms, in dogs, cats, horses, cattle and sheep. Moxidectin kills some of the most common internal and external ...
toxicosis.
Mechanism of action
All LAs are
membrane
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
-stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes (like
nociceptors
A nociceptor ("pain receptor" from Latin ''nocere'' 'to harm or hurt') is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sens ...
). Though many other drugs also have membrane-stabilizing properties, not all are used as LAs (
propranolol
Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anx ...
, for example, though it has LA properties).
LA drugs act mainly by inhibiting
sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
influx through sodium-specific
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
s in the
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
al
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
, in particular the so-called voltage-gated sodium channels. When the influx of sodium is interrupted, an
action potential
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
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
RAC 421-II, also referred to simply as RAC 421, is a quaternary local anesthetic that acts through intracellular blockage of the NaKATPase channel.
Function
As a quaternary ammonium analogue of another local anesthetic, RAC 109, 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 anaesthetic 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 never 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
In neuroscience and anatomy, nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, al ...
, 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.
[{{cite journal , vauthors = Henkel G , title = Susceptibility of Nerve Fibers to Local Anesthesia:“Size Principle” Challenged. , journal = The Journal of the American Society of Anesthesiologists , date = December 2001 , volume = 95 , issue = 6 , pages = 5A-6A , doi = 10.1097/00000542-200112000-00003 }]
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
Infiltration may refer to:
Science, medicine, and engineering
*Infiltration (hydrology), downward movement of water into soil
*Infiltration (HVAC), a heating, ventilation, and air conditioning term for air leakage into buildings
*Infiltration (me ...
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
Nerve block or regional nerve blockade is any deliberate interruption of signals traveling along a nerve, often for the purpose of pain relief. Local anesthetic nerve block (sometimes referred to as simply "nerve block") is a short-term block, u ...
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
A nerve plexus is a plexus (branching network) of intersecting nerves. A nerve plexus is composed of afferent and efferent fibers that arise from the merging of the anterior rami of spinal nerves and blood vessels. There are five spinal nerve ple ...
, 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
A spinal nerve is a mixed nerve, which carries motor, sensory, and autonomic signals between the spinal cord and the body. In the human body there are 31 pairs of spinal nerves, one on each side of the vertebral column. These are grouped into th ...
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
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
, usually at the lumbar spine (in the lower back), where it acts on spinal nerve
A spinal nerve is a mixed nerve, which carries motor, sensory, and autonomic signals between the spinal cord and the body. In the human body there are 31 pairs of spinal nerves, one on each side of the vertebral column. These are grouped into th ...
roots and part of the spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
; the resulting anesthesia usually extends from the legs to the abdomen or chest.
* Intravenous regional anesthesia
Intravenous regional anesthesia (IVRA) or Bier's block anesthesia is an anesthetic technique on the body's extremities where a local anesthetic is injected intravenously and isolated from circulation in a target area. The technique usually involv ...
(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.
{{anchor, catheter 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-Alkinosi Technique
The Vazirani-alkinosi 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 2 lengths; short and long. As Vazirani-akinosi is a local anaesthetic 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.[{{cite book, title=Handbook of local anesthesia, vauthors = Malamed SF , date=2013, publisher=Elsevier, isbn=9780323074131, edition=6th, location=St. Louis, Missouri, oclc=769141511, name-list-style=vanc]
Intraligamentary Infiltration
Intraligamentary infiltration, also known as periodontal ligament injection or intraligamentary injection (ILIs), 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:
1. Single-tooth anesthesia
2. Low anesthetic dose
3. Contraindication for systemic anesthesia
4. 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[{{cite journal , vauthors = Shabazfar N, Daubländer M, Al-Nawas B, Kämmerer PW , title = Periodontal intraligament injection as alternative to inferior alveolar nerve block--meta-analysis of the literature from 1979 to 2012 , journal = Clinical Oral Investigations , volume = 18 , issue = 2 , pages = 351–358 , date = 2014 , pmid = 24077785 , doi = 10.1007/s00784-013-1113-1 , s2cid = 9525498 ] and self-inflicted periodontal tissue injury,[{{cite journal , vauthors = Galili D, Kaufman E, Garfunkel AA, Michaeli Y , title = Intraligamentary anesthesia--a histological study , journal = International Journal of Oral Surgery , volume = 13 , issue = 6 , pages = 511–6 , date = December 1984 , pmid = 6439659 , doi = 10.1016/s0300-9785(84)80022-8 ] 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,[{{cite journal , vauthors = Roberts GJ, Holzel HS, Sury MR, Simmons NA, Gardner P, Longhurst P , title = Dental bacteremia in children , journal = Pediatric Cardiology , volume = 18 , issue = 1 , pages = 24–27 , date = January 1997 , pmid = 8960488 , doi = 10.1007/s002469900103 , s2cid = 7178684 ] 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, postoperative discomfort, and injury on unerupted teeth such as enamel hypoplasia and defects.
Technique description:
* All plaque and calculus to be eradicated, optimally before the operative visit to assist gingival tissue healing.
* Before injection, disinfect gingival sulcus with 0.2% chlorhexidine solution.
* 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.[{{cite journal , vauthors = Malamed SF , title = The periodontal ligament (PDL) injection: an alternative to inferior alveolar nerve block , journal = Oral Surgery, Oral Medicine, and Oral Pathology , volume = 53 , issue = 2 , pages = 117–121 , date = February 1982 , pmid = 6949113 , doi = 10.1016/0030-4220(82)90273-0 ]
* 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.[{{cite journal , vauthors = Meechan JG , title = How to overcome failed local anaesthesia , journal = British Dental Journal , volume = 186 , issue = 1 , pages = 15–20 , date = January 1999 , pmid = 10028738 , doi = 10.1038/sj.bdj.4800006 , s2cid = 6618968 ]
* 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.
Syringes:
* Standard syringes can be used.
* The intraligamentary syringe offers mechanical advantage by using a trigger-grasp or click apparatus to employ a gear or lever that improves control and results in increased force to push the anesthetic cartridge's rubber stopper forward for medication deposition with greater ease.
* C-CLADs (computer controlled local anesthetic delivery devices) can be used. Its usage of computer microprocessors allows for control of fluid dynamics and anesthetic deposition. This minimizes subjective flow rates and variability in pressure. This thereby results in enhanced hydrodynamic diffusion of solution into bone or the target area of deposition, 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 5mm 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.[{{cite journal , vauthors = Gow-Gates GA , title = The Gow-Gates mandibular block: regional anatomy and analgesia , journal = Australian Endodontic Journal , volume = 24 , issue = 1 , pages = 18–19 , date = April 1998 , pmid = 11431805 , doi = 10.1111/j.1747-4477.1998.tb00251.x ] 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-Gate technique, only 2 of them did not obtain complete anesthesia.
Types
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
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessel ...
possibly (see below)
* Reducing agent
In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ).
Examples of substances that are commonly reducing agents include the Earth meta ...
(antioxidant), e.g. if epinephrine is used, then sodium metabisulfite
Sodium metabisulfite or sodium pyrosulfite (IUPAC spelling; Br. E. sodium metabisulphite or sodium pyrosulphite) is an inorganic compound of chemical formula Na2S2O5. The substance is sometimes referred to as disodium metabisulfite. It is used a ...
is used as a reducing agent
* Preservative
A preservative is a substance or a chemical that is added to products such as food products, beverages, pharmaceutical drugs, paints, biological samples, cosmetics, wood, and many other products to prevent decomposition by microbial growth or by ...
, e.g. methylparaben
Methylparaben, also methyl paraben, one of the parabens, is a preservative with the chemical formula CH3(C6H4(OH)COO). It is the methyl ester of ''p''-hydroxybenzoic acid.
Natural occurrences
Methylparaben serves as a pheromone for a variety ...
* Buffer
Buffer may refer to:
Science
* Buffer gas, an inert or nonflammable gas
* Buffer solution, a solution used to prevent changes in pH
* Buffering agent, the weak acid or base in a buffer solution
* Lysis buffer, in cell biology
* Metal ion buffer
* ...
Esters are prone to producing allergic reactions, which may necessitate the use of an amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
. 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,[{{cite book , vauthors = Stern A , title=Pharmacology: PreTest self-assessment and review , url=https://archive.org/details/pharmacology00arno , url-access=registration , publisher=McGraw-Hill, Medical Pub. Division , location=New York , year=2002 , isbn=978-0-07-136704-2 ] although since cholinesterases are produced in the liver, physiologically (e.g. very young or very old individual) or pathologically (e.g. cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
) impaired hepatic metabolism is also a consideration when using esters.
Sometimes, LAs are combined, e.g.:
* Lidocaine/prilocaine
Lidocaine/prilocaine is a eutectic mixture of equal quantities (by weight) 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 (an ...
(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
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
. 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
Prilocaine () is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Löfgren. In its injectable form (trade name Citanest), it is often used in dentistry. It is also often combined with lidocaine as a topical p ...
hydrochloride and epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
(trade name
A trade name, trading name, or business name, is a pseudonym used by companies that do not operate under their registered company name. The term for this type of alternative name is a "fictitious" business name. Registering the fictitious name w ...
Citanest Forte)
* Lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
, bupivacaine, and epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
(recommended final concentrations of 0.5, 0.25, and 0.5%, respectively)
* Iontocaine
Iontocaine was an anesthetic medication, marketed under the two brand names Numby and Phoresor PM900 by IOMED inc. It is a local anesthetic with vasoconstrictor
A local anesthetic (LA) is a medication that causes absence of pain sensation. In ...
, 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
Tetracaine, also known as amethocaine, is an ester local anesthetic used to numb the eyes, nose, or throat. It may also be applied to the skin before starting an intravenous (injection) to decrease pain from the procedure. Typically it is applied ...
,1/2000 (0.05%, 500 ppm, {{frac, 1, 2 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
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
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.[{{cite journal , vauthors = Nielsen LJ, Lumholt P, Hölmich LR , title = ocal anaesthesia with vasoconstrictor is safe to use in areas with end-arteries in fingers, toes, noses and ears, journal = Ugeskrift for Laeger , volume = 176 , issue = 44 , pages = 44 , date = October 2014 , pmid = 25354008 ]
Ester group
* Benzocaine
Benzocaine, sold under the brand name Orajel amongst others, is an ester 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 such as products f ...
* Chloroprocaine
Chloroprocaine (trade name Nesacaine, Nesacaine-MPF) (often in the hydrochloride salt form as the aforementioned trade names) is a local anesthetic given by injection during surgical procedures and labor and delivery. Chloroprocaine vasodilates; t ...
* Cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
* Cyclomethycaine
Cyclomethycaine is a local anesthetic
A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of c ...
* Dimethocaine
Dimethocaine, also known as DMC or larocaine, is a compound with a stimulatory effect. This effect resembles that of cocaine, although dimethocaine appears to be less potent. Just like cocaine, dimethocaine is addictive due to its stimulation of ...
(Larocaine)
* Piperocaine
Piperocaine is a local anesthetic drug developed in the 1920s and used as its hydrochloride salt for infiltration and nerve blocks. Synthesis
Alkylation between 3-chloropropyl benzoate 42-95-0(1) and Pipicoline 09-05-7(2) provides piperocain ...
* Propoxycaine
* Procaine
Procaine is a local anesthetic drug of the amino ester group. It is most commonly used in dental procedures to numb the area around a tooth and is also used to reduce the pain of intramuscular injection of penicillin. Owing to the ubiquity ...
(Novocaine)
* Proparacaine
* Tetracaine
Tetracaine, also known as amethocaine, is an ester local anesthetic used to numb the eyes, nose, or throat. It may also be applied to the skin before starting an intravenous (injection) to decrease pain from the procedure. Typically it is applied ...
(Amethocaine)
Amide group
* Articaine
* Bupivacaine
* Cinchocaine
Cinchocaine (INN/ BAN) or dibucaine (USAN) is an amide local anesthetic. Among the most potent and toxic of the long-acting local anesthetics, current use of cinchocaine is generally restricted to spinal and topical anesthesia. It is sold under th ...
(Dibucaine)
* Etidocaine
Etidocaine, marketed under the trade name Duranest, is an amide-type local anesthetic given by injection during surgical procedures
Many surgical procedure names can be broken into parts to indicate the meaning. For example, in gastrectomy, "ect ...
* Levobupivacaine
Levobupivacaine (International Nonproprietary Name, rINN) is a local anaesthetic drug belonging to the amino amide group. It is the ''S''-enantiomer of bupivacaine.
Levobupivacaine hydrochloride is commonly marketed by AbbVie under the trade nam ...
* Lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
(Lignocaine)
* Mepivacaine
Mepivacaine is a local anesthetic of the amide type. Mepivacaine has a reasonably rapid onset (more rapid than that of procaine) and medium duration of action (shorter than that of procaine) and is marketed under various trade names including C ...
* Prilocaine
Prilocaine () is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Löfgren. In its injectable form (trade name Citanest), it is often used in dentistry. It is also often combined with lidocaine as a topical p ...
* Ropivacaine
Ropivacaine (rINN) is a local anaesthetic drug belonging to the amino amide group. The name ropivacaine refers to both the racemate and the marketed ''S''-enantiomer. Ropivacaine hydrochloride is commonly marketed by AstraZeneca under the brand na ...
* Trimecaine
Trimecaine (systematic name ''(2,4,6-trimethylphenylcarbamoylmethyl)diethylammonium chloride'', chemical formula C15H25ClN2O) is an organic compound used as a local anesthetic and cardial antiarrhythmic. It is white crystalline powder readily solu ...
Naturally derived
* Saxitoxin
Saxitoxin (STX) is a potent neurotoxin and the best-known paralytic shellfish toxin (PST). Ingestion of saxitoxin by humans, usually by consumption of shellfish contaminated by toxic algal blooms, is responsible for the illness known as paralytic ...
* Neosaxitoxin
Neosaxitoxin (NSTX) is included, as other saxitoxin-analogs, in a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs). The parent compound of PSTs, saxitoxin (STX), is a tricyclic perhydropurine al ...
* Tetrodotoxin
Tetrodotoxin (TTX) is a potent neurotoxin. Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish; several of these species carry the toxin. Although tetrodotoxin was discovered ...
* Menthol
Menthol is an organic compound, more specifically a monoterpenoid, made synthetically or obtained from the oils of corn mint, peppermint, or other mints. It is a waxy, clear or white crystalline substance, which is solid at room temperature and ...
* Eugenol
Eugenol is an allyl chain-substituted guaiacol, a member of the allylbenzene class of chemical compounds. It is a colorless to pale yellow, aromatic oily liquid extracted from certain essential oils especially from clove, nutmeg, cinnamon, basil ...
* Cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
* Spilanthol
Spilanthol is a fatty acid amide isolated from ''Acmella oleracea''. It is believed to be responsible for the local anesthetic properties of the plant.
Spilanthol permeates the human skin and the inside lining of the cheeks in the mouth (buccal ...
Most naturally occurring local anesthetics with the exceptions of menthol, eugenol and cocaine are neurotoxin
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
s, and have the suffix -toxin in their names. Cocaine binds the intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
side of the channels while saxitoxin, neosaxitoxin and tetrodotoxin bind to the extracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
side of sodium channels.
History
{{more citations needed section, date=February 2014
In Peru
, image_flag = Flag of Peru.svg
, image_coat = Escudo nacional del Perú.svg
, other_symbol = Great Seal of the State
, other_symbol_type = Seal (emblem), National seal
, national_motto = "Fi ...
, the ancient Incas
The Inca Empire (also Quechuan and Aymaran spelling shift, known as the Incan Empire and the Inka Empire), called ''Tawantinsuyu'' by its subjects, (Quechuan languages, Quechua for the "Realm of the Four Parts", "four parts together" ) wa ...
are believed to have used the leaves of the coca plant
Coca is any of the four cultivated plants in the family Erythroxylaceae, native to western South America. Coca is known worldwide for its psychoactive alkaloid, cocaine.
The plant is grown as a cash crop in the Argentine Northwest, Bolivia, Al ...
as a local anaesthetic in addition to its stimulant properties.[{{cite news , vauthors = Gazourian A , title=Cocaine's use: From the Incas to the U.S., url=https://news.google.com/newspapers?nid=1291&dat=19850404&id=0B1UAAAAIBAJ&pg=6387,881236, access-date=2 February 2014, newspaper=Boca Raton News, date=4 April 1985] 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. Cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
was 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 anesthetics stovaine in 1903 and procaine
Procaine is a local anesthetic drug of the amino ester group. It is most commonly used in dental procedures to numb the area around a tooth and is also used to reduce the pain of intramuscular injection of penicillin. Owing to the ubiquity ...
in 1904. Since then, several synthetic local anesthetic drugs have been developed and put into clinical use, notably lidocaine in 1943, bupivacaine in 1957, and prilocaine in 1959.
The invention of clinical use of local anaesthesia is credited to the Vienna School which included Sigmund Freud (1856-1939), Carl Koller (1857-1944) and Leopold Konigstein (1850-1942). They introduced local anaesthesia, using cocaine, through 'self-experimation' on their oral mucosa before introducing it to animal or human experimentation. The Vienna school first started using cocaine as local anaesthesia in ophthalmology and it was later incorporated into ophthalmologic practice. Dr. Halsted and Dr. Hall, in the United States in 1885 described an intraoral anaesthetic technique of blocking the inferior alveolar nerve and the antero-superior dental nerve using 4% cocaine.{[{{cite journal , vauthors = López-Valverde A, de Vicente J, Martínez-Domínguez L, de Diego RG , title = Local anaesthesia through the action of cocaine, the oral mucosa and the Vienna group , journal = British Dental Journal , volume = 217 , issue = 1 , pages = 41–43 , date = July 2014 , pmid = 25012333 , doi = 10.1038/sj.bdj.2014.546 , doi-access = free ]
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 Karl Gustav Bier (24 November 1861 – 12 March 1949) was a German surgeon. He was the first to perform spinal anesthesia and intravenous regional anesthesia.
Early medical career
Bier began his medical education at the Charité – Uni ...
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
Fidel Pagés Miravé (26 January 1886 – 21 September 1923) was a Spanish military surgeon, known for developing the technique of epidural anesthesia.
He practised a wide range of traumatological and surgical techniques, both for war injuries an ...
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
* Amylocaine
Amylocaine was the first synthetic local anesthetic. It was synthesized and patented under the name Stovaine by Ernest Fourneau at the Pasteur Institute in 1903. It was used mostly in spinal anesthesia.Debue-Barazer, Christine (2007)"Les Implicatio ...
* Anesthetic
* General anesthetic
General anaesthetics (or anesthetics, see spelling differences) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma ...
* List of cocaine analogues
This is a list of cocaine analogues. A cocaine analogue is an (usually) artificial construct of a novel chemical compound from (often the starting point of natural) cocaine's molecular structure, with the result product sufficiently similar to co ...
* List of local anesthetics
This is a list of local anesthetic agents. Not all of these drugs are still used in clinical practice and in research. Some are primarily of historical interest.
See also
* 4-Aminobenzoic acid
* Amino amide
* Amino esters
* Anesthesia
* Anest ...
References
{{Reflist, 30em
External links
The American Society of Regional Anesthesia
{{Major drug groups
{{Local anesthetics
{{Neuropathic pain and fibromyalgia pharmacotherapies
{{Anesthesia
{{Authority control
Anesthesia