general anaesthetic general anaesthetic 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 that causes lack of awareness to painful stimuli, sufficient to facilitate surgical applications in clinical and veterinary practice. general anaesthetics do not act as analgesics and should also not be confused with sedatives. general anaesthetics are a structurally diverse group of compounds whose mechanisms encompasses multiple biological targets involved in the control of neuronal pathways. the precise workings are the subject of some debate and ongoing research. these drugs are not to be confused with sleep medicine for insomnia. general anesthetics elicit a state of general anesthesia. it remains somewhat controversial regarding how this state should be defined. general anesthetics, however, typically elicit several key reversible effects: immobility, analgesia, amnesia, unconsciousness, and reduced autonomic responsiveness to noxious stimuli. mode of administration general anaesthetics can be administered either as gases or vapours (inhalational anaesthetics), or as injections (intravenous anaesthetics or even intramuscular). all of these agents share the property of being quite hydrophobic (i.e., as liquids, they are not freely miscible—or mixable—in water, and as gases they dissolve in oils better than in water). it is possible to deliver anaesthesia solely by inhalation or injection, but most commonly the two forms are combined, with an injection given to induce anaesthesia and a gas used to maintain it. inhalation general anesthetics are frequently administered as volatile liquids or gases inhalational anaesthetic substances are either volatile liquids or gases, 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 vapourised in the machine. many compounds have been used for inhalation anaesthesia, but only a few are still in widespread use. desflurane, isoflurane and sevoflurane are the most widely used volatile anaesthetics today. they are often combined with nitrous oxide. older, less popular, volatile anaesthetics, include halothane, enflurane, and methoxyflurane. researchers are also actively exploring the use of xenon as an anaesthetic. injection injectable anaesthetics are used for the 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 or subcutaneous injections. among the most widely used drugs are: propofol etomidate barbiturates such as methohexital and thiopentone/thiopental benzodiazepines such as midazolam ketamine is used in the uk as "field anaesthesia", for instance in road traffic incidents or similar situations where an operation must be conducted at the scene or when there is not enough time to move to an operating room, while preferring other anaesthetics where conditions allow their use. it is more frequently used in the operative setting in the us. benzodiazepines are sedatives and are used in combinations with other general anaesthetics mechanism of action induction and maintenance of general anesthesia, and the control of the various physiological side effects is typically achieved through a combinatorial drug approach. individual general anesthetics vary with respect to their specific physiological and cognitive effects. while general anesthesia induction may be facilitated by one general anesthetic, others may be used in parallel or subsequently to achieve and maintain the desired anesthetic state. the drug approach utilized is dependent upon the procedure and the needs of the healthcare providers. it is postulated that general anaesthetics exert their action by the activation of inhibitory central nervous system (cns) receptors, and the inactivation of cns excitatory receptors. the relative roles of different receptors is still under debate, but evidence exists for particular targets being involved with certain anaesthetics and drug effects. below are several key targets of general anesthetics that likely mediate their effects: gabaa receptor agonists gabaa receptors are chloride channels that hyperpolarize neurons and function as inhibitory cns receptors. general anesthetics that agonize them are typically used to induce a state of sedation and/or unconsciousness. such drugs include propofol, etomidate, isoflurane, benzodiazepines (midazolam, lorazepam, diazepam), and barbiturates (sodium thiopental, methohexital). nmda receptor antagonists ketamine, an nmda receptor antagonist, is used primarily for its analgesic effects and in an off-label capacity for its anti-depressant effects. this drug, however, also alters arousal and is often used in parallel with other general anesthetics to help maintain a state of general anesthesia. administration of ketamine alone leads to a dissociative state, in which a patient may experience auditory and visual hallucinations. additionally, the perception of pain is dissociated from the perception of noxious stimuli. ketamine appears to bind preferentially to the nmda receptors on gabaergic interneurons, which may partially explain its effects. two-pore potassium channels (k2ps) activation two-pore potassium channels (k2ps) modulate the potassium conductance that contributes to the resting membrane potential in neurons. opening of these channels therefore facilitates a hyperpolarizing current, which reduces neuronal excitability. k2ps have been found to be affected by general anesthetics (esp. halogenated inhalation anesthetics) and are currently under investigation as potential targets. the k2p channel family comprises six subfamilies, which includes 15 unique members. 13 of these channels (excluding twik-1 and twik-2 homomers) are affected by general anesthetics. while it has not been determined that general anesthetics bind directly to these channels, nor is it clear how these drugs affect k2p conductance, electrophysiological studies have shown that certain general anesthetics result in k2p channel activation. this drug-elicited channel activation has been shown to be dependent upon specific amino-acids within certain k2p channels (i.e. trek-1 and task channels). in the case of trek-1, activation was shown through an anesthetic perturbation to membrane lipid clusters and activation of phospholipase d2; direct binding of anesthetics to purified reconstituted trek-1 had no effect on conductance. the effects of certain general anesthetics are less pronounced in k2p knock-out mice, as compared to their wild-type counterparts. cumulatively, task-1, task-3, and trek-1 are particularly well supported as playing a role in the induction of general anesthesia. others opioid receptor agonists are primarily utilized for their analgesic effects. these drugs, however, can also elicit sedation. this effect is mediated by opioid actions on both opioid and acetylcholine receptors. while these drugs can lead to decreased arousal, they do not elicit a loss of consciousness. for this reason, they are often used in parallel with other general anesthetics to help maintain a state of general anesthesia. such drugs include morphine, fentanyl, hydromorphone, and remifentanil. administration of the alpha2 adrenergic receptor agonist dexmedetomidine leads to sedation that resembles non-rem sleep. it is used in parallel with other general anesthetics to help maintain a state of general anesthesia, in an off-label capacity. notably, patients are easily aroused from this non-rem sleep state. dopamine receptor antagonists have sedative and antiemetic properties. previously, they were used in parallel with opioids to elicit neuroleptic anesthesia (catalepsy, analgesia, and unresponsiveness). they are no longer used in the context, because patients experiencing neuroleptic anesthesia were frequently aware of the medical procedures being performed, but could not move or express emotion. such drugs include haloperidol and droperidol.