General anaesthetic
Encyclopedia
A general anaesthetic is a drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 that brings about a reversible loss of consciousness
Consciousness
Consciousness is a term that refers to the relationship between the mind and the world with which it interacts. It has been defined as: subjectivity, awareness, the ability to experience or to feel, wakefulness, having a sense of selfhood, and the executive control system of the mind...

. These drugs are generally administered by an anaesthesia provider to induce or maintain general anaesthesia
General anaesthesia
General anaesthesia is a state of unconsciousness and loss of protective reflexes resulting from the administration of one or more general anaesthetic agents...

 to facilitate surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

. The biological mechanism(s) of the action of general anaesthetics are not well understood.

Mode of administration

Drugs given to induce or maintain general anaesthesia are either given as:
  • Gases or vapours (inhalational anaesthetic
    Inhalational anaesthetic
    An inhalational anaesthetic is a chemical compound possessing general anaesthetic properties that can be delivered via inhalation. They are administered by anaesthetists through an anaesthesia mask, laryngeal mask airway or tracheal tube connected to some type of anaesthetic vaporiser and an...

    s)
  • Injections (intravenous anaesthetics)


Most commonly, these two forms are combined, with an injection given to induce anaesthesia and a gas used to maintain it, although it is possible to deliver anaesthesia solely by inhalation or injection.

Inhalation

Inhalational anaesthetic substances are either volatile
Volatility (chemistry)
In chemistry and physics, volatility is the tendency of a substance to vaporize. Volatility is directly related to a substance's vapor pressure. At a given temperature, a substance with higher vapor pressure vaporizes more readily than a substance with a lower vapor pressure.The term is primarily...

 liquid
Liquid
Liquid is one of the three classical states of matter . Like a gas, a liquid is able to flow and take the shape of a container. Some liquids resist compression, while others can be compressed. Unlike a gas, a liquid does not disperse to fill every space of a container, and maintains a fairly...

s or gas
Gas
Gas is one of the three classical states of matter . Near absolute zero, a substance exists as a solid. As heat is added to this substance it melts into a liquid at its melting point , boils into a gas at its boiling point, and if heated high enough would enter a plasma state in which the electrons...

es, and are usually delivered using an anaesthesia machine. An anaesthesia machine allows composing a mixture of oxygen, anaesthetics and ambient air, delivering it to the patient and monitoring patient and machine parameters. Liquid anaesthetics are vapourized in the machine.

Many compounds have been used for inhalation anaesthesia, but only a few are still in widespread use. Desflurane
Desflurane
Desflurane is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane and isoflurane, it is a racemic mixture of and optical isomers...

, isoflurane
Isoflurane
Isoflurane is a halogenated ether used for inhalational anesthesia. Together with enflurane and halothane, it replaced the flammable ethers used in the pioneer days of surgery. Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula...

 and sevoflurane
Sevoflurane
Sevoflurane , also called fluoromethyl hexafluoroisopropyl ether, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology...

 are the most widely used volatile anaesthetics today. They are often combined with nitrous oxide
Nitrous oxide
Nitrous oxide, commonly known as laughing gas or sweet air, is a chemical compound with the formula . It is an oxide of nitrogen. At room temperature, it is a colorless non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...

. Older, less popular, volatile anaesthetics, include halothane
Halothane
Halothane is an inhalational general anesthetic. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic agent containing a bromine atom; there are several other halogenated anesthesia agents which lack the bromine atom and do contain the fluorine and...

, enflurane
Enflurane
Enflurane is a halogenated ether that was commonly used for inhalational anesthesia during the 1970s and 1980s. Developed by Ross Terrell in 1963, it was first used clinically in 1966....

, and methoxyflurane
Methoxyflurane
Methoxyflurane is a halogenated ether that was in clinical use as an volatile inhalational anesthetic from its introduction by Joseph F. Artusio et al in 1960 until around 1974. It was first synthesized in the late 1940s by William T...

. Researchers are also actively exploring the use of xenon
Xenon
Xenon is a chemical element with the symbol Xe and atomic number 54. The element name is pronounced or . A colorless, heavy, odorless noble gas, xenon occurs in the Earth's atmosphere in trace amounts...

 as an anaesthetic.

Injection

Injection anaesthetics are used for induction and maintenance of a state of unconsciousness. Anaesthetists prefer to use intravenous injections, as they are faster, generally less painful and more reliable than intramuscular
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...

 or subcutaneous injection
Subcutaneous injection
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the...

s. Among the most widely used drugs are:
  • Propofol
    Propofol
    Propofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...

  • Etomidate
    Etomidate
    Etomidate is a short acting intravenous anaesthetic agent used for the induction of general anaesthesia and for sedation for short procedures such as reduction of dislocated joints, tracheal intubation and cardioversion...

  • Barbiturate
    Barbiturate
    Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...

    s such as methohexital
    Methohexital
    Methohexital, also called methohexitone, is a drug which is a barbiturate derivative. It is classified as short-acting, and has a rapid onset of action...

     and thiopentone/thiopental
  • Benzodiazepine
    Benzodiazepine
    A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...

    s such as midazolam
    Midazolam
    Midazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...

  • Ketamine
    Ketamine
    Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

     is used in the UK as "field anaesthesia", for instance at a road traffic incidents, and is more frequently used in the operative setting in the US.


The volatile anaesthetics are a class of general anaesthetic drugs composed of gasses and liquids which evaporate easily for administration by inhalation. All of these agents share the property of being quite hydrophobic (i.e., as liquids, they are not freely miscible with in water, and as gases they dissolve in oils better than in water).

Lipid theory

Overton and Meyer postulated general anaesthetics exert their action by acting on the plasma membrane. This is supported by evidence that the potency of the drug has a direct, positive correlation with the lipid solubility of the blood.

The mechanism of action was proposed to be increased fluidity of the membrane. The interpretation of the Overton and Meyer finding has been challenged and discredited.

Ion channels

General anaesthetics inhibit excitatory functions of some 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...

 (CNS) receptors, such as neuronal nACh, glutamate, or 5-HT3 receptors. Some general anaesthetics also excite inhibitory receptors, notably GABAA receptors and TREK. GABAA is a major target of the IV anaesthetics thiopental and propofol
Propofol
Propofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...

.

General anaesthetics may decrease transmitter release presynaptically or decrease excitability of postsynaptic neuron.

Elimination

Volatile anaesthetics are eliminated in the terminal phase via the lungs. A low blood:gas coefficient is therefore necessary for quick removal of the anaesthetic. When the oil:water coefficient is high, there will be little anaesthetic in the blood, so elimination will be slow, giving a prolonged hangover effect.

Some drugs are metabolised by the liver, so consequently their metabolites are often toxic (e.g. chloroform
Chloroform
Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...

).

See also

  • Local anaesthesia
    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...

  • Mechanical ventilation
    Mechanical ventilation
    In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...

  • Intraoperative awareness
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