View source for Anesthetic

{{short description|Drug that causes anesthesia}}
{{Distinguish|aesthetics|analgesic}}
{{redirect|Anesthetics|the practice of using anesthetic drugs and anesthesia|Anesthesiology}}
{{about|anesthetics, drugs that provide anesthesia|the 2019 album by Mark Morton|Anesthetic (album)}}
{{Use dmy dates|date=March 2018}}
[[File:Erythroxylum_novogranatense_var._Novogranatense_(retouched).jpg|thumb|right|Leaves of the [[coca]] plant (''Erythroxylum novogranatense'' var. ''Novogranatense''), from which [[cocaine]], a naturally occurring local anesthetic, is derived<ref>{{Cite journal|last=Goldberg|first=MF|date=1984|title=Cocaine: The First Local Anesthetic and the'Third Scourge of Humanity': A Centennial Melodrama|url=https://scholar.google.com/scholar_lookup?journal=Arch+Ophthalmol.&title=Cocaine:+the+first+local+anesthetic+and+the+%27third+scourge+of+humanity%27.+A+centennial+melodrama.&author=MF+Goldberg&volume=102&issue=10&publication_year=1984&pages=1443-7&pmid=6385930&|journal=Archives of Ophthalmology|volume=102|issue=10|pages=1443–1447|doi=10.1001/archopht.1984.01040031163009|pmid=6385930|via=jamanetwork.com|url-access=subscription}}</ref><ref>{{Cite book|last=Karch|first=SB|title=A brief history of cocaine.|publisher=CRC press|year=1998|url=https://scholar.google.com/scholar_lookup?title=A+brief+history+of+cocaine.&author=SB.+Karch&publication_year=1998&}}</ref>]]
An '''anesthetic''' ([[American English]]) or '''anaesthetic''' ([[British English]]; [[American and British English spelling differences#Miscellaneous spelling differences|see spelling differences]]) is a [[drug]] used to induce [[anesthesia]] ⁠— ⁠in other words, to result in a temporary loss of [[sense|sensation]] or [[awareness]]. They may be divided into two broad classes: [[general anesthetic]]s, which result in a reversible loss of [[consciousness]], and [[local anesthetic]]s, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.<ref>{{Ullmann |doi=10.1002/14356007.a02_289|title=Anesthetics, General|year=2000|last1=Wollweber|first1=Hartmund}}</ref><ref name=":0">{{Cite book |last=Butterworth |first=John |title=Morgan & Mikhail's Clinical Anesthesiology |last2=Mackey |first2=David |last3=Wasnick |first3=John |date= |publisher=[[McGraw Hill Education]] |year=2013 |isbn=978-0-07-171405-1 |edition=5th}}</ref>

A wide variety of drugs are used in modern anesthetic practice.  Many are rarely used outside [[anesthesiology]], but others are used commonly in various fields of healthcare. Combinations of anesthetics are sometimes used for their [[synergy|synergistic]] and [[drug interaction#Synergy and antagonism|additive]] therapeutic effects. Adverse effects, however, may also be increased.<ref name="Hendrickx-2008">{{Cite journal | last1 = Hendrickx | first1 = JF. | last2 = Eger | first2 = EI. | last3 = Sonner | first3 = JM. | last4 = Shafer | first4 = SL. | title = Is synergy the rule? A review of anesthetic interactions producing hypnosis and immobility. | url = http://www.anesthesia-analgesia.org/content/107/2/494.long | journal = Anesth Analg | volume = 107 | issue = 2 | pages = 494–506 |date=August 2008 | doi = 10.1213/ane.0b013e31817b859e | pmid = 18633028 | s2cid = 8125002 | doi-access = free }}</ref>  Anesthetics are distinct from [[analgesics]], which block only sensation of [[pain]]ful stimuli.<ref>{{cite web |title=Reducing Animals' Pain and Distress {{!}} National Agricultural Library |url=https://www.nal.usda.gov/animal-health-and-welfare/animal-use-alternatives/reducing-animals-pain-and-distress |website=www.nal.usda.gov |access-date=28 January 2023 |language=en |date=2022 }}</ref><ref name=":0" /> Analgesics are typically used in conjunction with anesthetics to control pre-, intra-, and postoperative pain.'''<ref name=":0" />'''

== Local anesthetics ==
{{Main|Local anesthetic}}

=== Ester-based ===

* [[Benzocaine]]
* [[Cocaine]] 

* [[Procaine]]
* [[Tetracaine]] (sometimes called [[Amethocaine]])

=== Amide-Based ===

* [[Bupivacaine]]
* [[Cinchocaine]]([[International Nonproprietary Name|INN]]/[[British Approved Name|BAN]])/[[Dibucaine]]([[United States Adopted Name|USAN]])
* [[Etidocaine]]
* [[Levobupivacaine]]
* [[Lidocaine]]
* [[Mepivacaine]]
* [[Prilocaine]]
* [[Ropivacaine]]

Local anesthetic agents prevent the transmission of nerve impulses without causing unconsciousness. They act by reversibly binding to fast [[sodium channels]] from within [[nerve fiber]]s, thereby preventing sodium from entering the fibres, stabilising the cell membrane and preventing [[action potential]] propagation. Each of the local anesthetics has the suffix "–caine" in their names.

Local anesthetics can be either [[ester]]- or [[amide]]-based. Ester local anesthetics are generally unstable in solution and fast-acting, are rapidly metabolised by [[Cholinesterase|cholinesterases]] in the [[blood plasma]] and [[liver]],<ref name=":0" /> and more commonly induce [[Allergic reaction|allergic reactions]]. Amide local anesthetics are generally heat-stable, with a long shelf life (around two years). Amides have a slower onset and longer half-life than ester anesthetics,<ref name=":0" /> and are usually [[racemic]] mixtures, with the exception of levobupivacaine (which is S(-) -bupivacaine)<ref name=":0" /> and ropivacaine (S(-)-ropivacaine). Although general rules exist for onset and duration of anesthesia between [[ester]]- or [[amide]]-based local anesthetics, these are properties are ultimately dependent on myriad factors including the lipid solubility of the agent, the concentration of the solution, and the [[PKa|p''K''<sub>a</sub>]].<ref name=":0" /> Amides are generally used within regional and epidural or spinal techniques,<ref name=":0" /> due to their longer duration of action, which provides adequate analgesia for surgery, labor, and symptomatic relief. Some esters, such as [[benzocaine]] and [[tetracaine]], are found in topical formulations to be absorbed through the skin.<ref name=":0" />

Only [[preservative]]-free local anesthetic agents may be injected [[intrathecal]]ly.

[[Pethidine]] also has local anesthetic properties, in addition to its opioid effects.<ref>{{cite journal|last1=Latta|first1=KS|last2=Ginsberg|first2=B|last3=Barkin|first3=RL|title=Meperidine: a critical review.|journal=[[American Journal of Therapeutics]]|date=2001|volume=9|issue=1|pages=53–68|pmid=11782820|doi=10.1097/00045391-200201000-00010|s2cid=23410891}}</ref>


== General anesthetics ==
[[File:Fluranebottles.jpg|alt=Bottles of sevoflurane, isoflurane, enflurane and desflurane, the most common fluorinated ether (flurane) inhalation anesthetics.|thumb|Bottles of sevoflurane, isoflurane, enflurane and desflurane, the most common fluorinated ether (flurane) inhalation anesthetics. Fluranes are color-coded – sevoflurane is marked yellow, isoflurane purple, enflurane orange and desflurane blue. The notches visible below the bottle caps are unique to each agent, ensuring that a vaporizer can only be filled with the correct agent.<ref name=":1">{{Ullmann|doi=10.1002/14356007.a02_289|title=Anesthetics, General|year=2000|last1=Wollweber|first1=Hartmund}}</ref><ref name=":0" />]]
{{Main|General anaesthetic}}

=== Inhaled agents ===
{{Main|Inhalational anaesthetic}}
* [[Desflurane]] (common)
* [[Enflurane]] (largely discontinued)
* [[Halothane]] (inexpensive, discontinued)
* [[Isoflurane]] (common)
* [[Methoxyflurane]]
* [[Nitrous oxide]]
* [[Sevoflurane]] (common)
* [[Xenon#Anesthesia|Xenon]] (rarely used)
[[Volatile anaesthetic|Volatile agents]] are typically organic liquids that evaporate readily. They are given by inhalation for induction or maintenance of general anesthesia. Nitrous oxide and xenon are gases, so they are not considered volatile agents. The ideal volatile anesthetic should be non-flammable, non-explosive, and lipid-soluble. It should possess low blood gas solubility, have no [[Organ (biology)|end-organ]] (heart, liver, kidney) toxicity or side-effects, should not be metabolized, and should not irritate the respiratory pathways.{{citation needed|date=February 2022}}

No anaesthetic agent currently in use meets all these requirements, nor can any anaesthetic agent be considered completely ''safe''. There are inherent risks and drug interactions that are specific to each and every patient.<ref>{{Cite journal | last1 = Krøigaard | first1 = M. | last2 = Garvey | first2 = LH. | last3 = Menné | first3 = T. | last4 = Husum | first4 = B.| title = Allergic reactions in anaesthesia: are suspected causes confirmed on subsequent testing?
 | journal = Br J Anaesth | volume = 95 | issue = 4 | pages = 468–71 |date=October 2005 | doi=10.1093/bja/aei198 | pmid=16100238| doi-access = free }}</ref> The agents in widespread current use are [[isoflurane]], [[desflurane]], [[sevoflurane]], and nitrous oxide. Nitrous oxide is a common [[adjuvant]] gas, making it one of the most long-lived drugs still in current use. Because of its low potency, it cannot produce anesthesia on its own but is frequently combined with other agents. Halothane, an agent introduced in the 1950s, has been almost completely replaced in modern anesthesia practice by newer agents because of its shortcomings.<ref name="town">{{cite book | last = Townsend | first = Courtney | title = Sabiston Textbook of Surgery | publisher = Saunders | location = Philadelphia | pages = Chapter 17 – Anesthesiology Principles, Pain Management, and Conscious Sedation | year = 2004 | isbn = 0-7216-5368-5 | no-pp = true }}</ref> Partly because of its side effects, enflurane never gained widespread popularity.<ref name="town"/>

In theory, any inhaled anesthetic agent can be used for induction of general anesthesia. However, most of the halogenated anesthetics are irritating to the airway, perhaps leading to coughing, laryngospasm and overall difficult inductions.  If induction needs to be conducted with an inhaled anesthetic agent, [[sevoflurane]] is often used due to a relatively low pungency, rapid increase in alveolar concentration, and a higher blood solubility than other agents. These properties allow for a less irritating and quicker induction as well as a rapid emergence from anesthesia compared to other inhaled agents.<ref name=":0" /> All of the volatile agents can be used alone or in combination with other medications to maintain anesthesia (nitrous oxide is not potent enough to be used as a sole agent).

Volatile agents are frequently compared in terms of potency, which is inversely proportional to the [[minimum alveolar concentration]]. Potency is directly related to lipid solubility. This is known as the [[Minimum alveolar concentration|Meyer-Overton hypothesis]]. However, certain pharmacokinetic properties of volatile agents have become another point of comparison. Most important of those properties is known as the [[blood/gas partition coefficient]]. This concept refers to the relative solubility of a given agent in blood. Those agents with a lower blood solubility (i.e., a lower blood–gas partition coefficient; e.g., desflurane) give the anesthesia provider greater rapidity in titrating the depth of anesthesia, and permit a more rapid emergence from the anesthetic state upon discontinuing their administration. In fact, newer volatile agents (e.g., sevoflurane, desflurane) have been popular not due to their potency (minimum alveolar concentration), but due to their versatility for a faster emergence from anesthesia, thanks to their lower blood–gas partition coefficient.

===Intravenous agents (non-opioid)===
While there are many drugs that can be used intravenously to produce anesthesia or sedation, the most common are:
* [[Barbiturate]]s
** [[Amobarbital]] ([[trade name]]: Amytal)
** [[Methohexital]] (trade name: Brevital)
** [[Thiamylal]] (trade name: Surital)
** [[Sodium thiopental|Thiopental]] (trade name: Penthothal, referred to as ''thiopentone'' in the UK)
* [[Benzodiazepines]]
** [[Diazepam]]
** [[Lorazepam]]
** [[Midazolam]]
* [[Etomidate]]
* [[Ketamine]]
* [[Propofol]]

Among the barbiturates mentioned above, [[Sodium thiopental|thiopental]] and [[methohexital]] are ultra-short-acting and are used to induce and maintain anesthesia.<ref name="miller2">{{cite book |last=Miller |first=Ronald |url=https://archive.org/details/millersanesthesi0006unse |title=Miller's Anesthesia |publisher=Elsevier/Churchill Livingstone |year=2005 |isbn=0-443-06656-6 |location=New York |url-access=registration}}</ref> However, though they produce unconsciousness, they provide no [[analgesia]] (pain relief) and must be used with other agents.<ref name="miller2" /> Benzodiazepines can be used for [[sedation]] before or after surgery and can be used to induce and maintain general anesthesia.<ref name="miller2" /> When benzodiazepines are used to induce general anesthesia, midazolam is preferred.<ref name="miller2" /> Benzodiazepines are also used for sedation during procedures that do not require general anesthesia.<ref name="miller2" /> Like barbiturates, benzodiazepines have no pain-relieving properties.<ref name="miller2" />

[[Etomidate]] is one of the most commonly used intravenous drugs employed to induce and maintain general anesthesia.<ref name="miller2" /> It can also be used for sedation during procedures or in the [[Intensive care unit|ICU]].<ref name="miller2" /> Like the other agents mentioned above, it renders patients unconscious without producing pain relief.<ref name="miller2" /> Compared to other IV agents, etomidate causes minimal depression of the cardiopulmonary system. Additionally, etomidate results in a reduction in intracranial pressure and cerebral blood flow.<ref name=":0" /> Because of these favorable physiological effects, was a favored agent in the ICU. However, etomidate has since been shown to produce adrenocortical suppression, resulting in decreased use to avoid an increased mortality rate in severely ill patients.<ref name=":0" /> Ketamine is infrequently used in anesthesia because of the unpleasant experiences that sometimes occur on emergence from anesthesia, which include "vivid [[Dream|dreaming]], extracorporeal experiences, and [[Illusion|illusions]]."<ref>{{cite journal |last1=Garfield |first1=JM |last2=Garfield |first2=FB |last3=Stone |first3=JG |last4=Hopkins |first4=D |last5=Johns |first5=LA |year=1972 |title=A comparison of psychologic responses to ketamine and thiopental-nitrous oxide-halothane anesthesia |journal=Anesthesiology |volume=36 |issue=4 |pages=329–338 |doi=10.1097/00000542-197204000-00006 |pmid=5020642 |s2cid=2526481 |doi-access=free}}</ref> When it is used, it is often paired with a benzodiazepine such as [[midazolam]] for amnesia and sedation.<ref name=":0" /> However, like etomidate it is frequently used in emergency settings and with sick patients because it produces fewer adverse physiological effects.<ref name="miller2" /> Unlike the intravenous anesthetic drugs previously mentioned, ketamine produces profound pain relief, even in doses lower than those that induce general anesthesia.<ref name="miller2" /> Also unlike the other anesthetic agents in this section, patients who receive ketamine alone appear to be in a [[Catalepsy|cataleptic]] state, unlike other states of anesthesia that resemble normal [[sleep]]. Ketamine-anesthetized patients have profound analgesia but keep their eyes open and maintain many reflexes.<ref name="miller2" />

== Intravenous opioid analgesic agents ==
While opioids can produce unconsciousness, they do so unreliably and with significant side effects.<ref>{{cite journal | doi = 10.1097/00000542-199007000-00002 | last1 = Philbin | first1 = DM | last2 = Rosow | first2 = CE | last3 = Schneider | first3 = RC | last4 = Koski | year = 1990 | first4 = G | last5 = D'ambra | first5 = MN | title =Fentanyl and sufentanil anesthesia revisited: how much is enough? | journal = Anesthesiology | volume = 73 | issue = 1| pages = 5–11 | pmid = 2141773 | doi-access = free }}</ref><ref name="pmid8466061">{{cite journal | vauthors = Streisand JB, Bailey PL, LeMaire L, Ashburn MA, Tarver SD, Varvel J, Stanley TH | title = Fentanyl-induced rigidity and unconsciousness in human volunteers. Incidence, duration, and plasma concentrations | journal = Anesthesiology | volume = 78 | issue = 4 | pages = 629–34 | date = April 1993 | pmid = 8466061 | doi = 10.1097/00000542-199304000-00003| s2cid = 32056642 | doi-access = free }}</ref> So, while they are rarely used to induce anesthesia, they are frequently used along with other agents such as intravenous non-opioid anesthetics or inhalational anesthetics.<ref name="miller2" /> Furthermore, they are used to relieve pain of patients before, during, or after surgery. The following opioids have short onset and duration of action and are frequently used during general anesthesia:
* [[Alfentanil]]
* [[Fentanyl]]
* [[Remifentanil]]
* [[Sufentanil]], which is not available in Australia.

The following agents have longer onset and duration of action and are frequently used for post-operative pain relief:
* [[Buprenorphine]]
* [[Butorphanol]]
* [[Diamorphine]], also known as heroin, not available for use as an analgesic in any country but the UK.
* [[Hydromorphone]]
* [[Levorphanol]]
* [[Pethidine]], also called meperidine in North America.
* [[Methadone]]
* [[Morphine]]
* [[Codeine]]
* [[Nalbuphine]]
* [[Oxycodone]], not available intravenously in U.S.
* [[Oxymorphone]]
* [[Pentazocine]]

== Muscle relaxants ==
{{Main|Neuromuscular blocking drugs}}
Muscle relaxants do not render patients unconscious or relieve pain. Instead, they are sometimes used after a patient is rendered unconscious (induction of anesthesia) to facilitate [[intubation]] or surgery by paralyzing skeletal muscle.<ref name=":0" />These agents fall into two categories: depolarizing agents, which depolarize the [[motor end plate]] to prevent further stimulation, and non-depolarizing agents, which prevent acetylcholine receptor activation through competitive inhibition.<ref name=":0" />
* Depolarizing muscle relaxants
** [[Succinylcholine]] (also known as '''suxamethonium''' in the UK, New Zealand, Australia and other countries, "Celokurin" or "celo" for short in Europe)
** [[Decamethonium]]
* Non-depolarizing muscle relaxants
** Short acting
*** [[Mivacurium]]
*** [[Rapacuronium]]
** Intermediate acting
*** [[Atracurium]]
*** [[Cisatracurium]]
*** [[Rocuronium]]
*** [[Vecuronium]]
** Long acting
*** [[Alcuronium]]
*** [[Doxacurium]]
*** [[Gallamine]]
*** [[Metocurine]]
*** [[Pancuronium]]
*** [[Pipecuronium]]
*** [[Tubocurarine]]

A potential complication where neuromuscular blockade is employed is '[[anesthesia awareness]]'.<ref name=":0" /> In this situation, patients paralyzed may awaken during their anesthesia, due to an inappropriate decrease in the level of drugs providing sedation or pain relief. If this is missed by the anesthesia provider, the patient may be aware of their surroundings, but be incapable of moving or communicating that fact. Neurological monitors are increasingly available that may help decrease the incidence of awareness. Most of these monitors use proprietary algorithms monitoring brain activity via evoked potentials. Additionally, anesthesia providers often have steps they follow to help prevent awareness, such as ensuring all equipment is working properly, monitoring that drugs are being delivered during surgery, and asking a series of questions (the Brice questions) to help detect awareness after surgery.<ref name=":0" /> If there is any suspicion of patient awareness, close follow-up and mental health professionals can help manage or avoid any traumatic stress associated with the awareness.<ref name=":0" /> Certain procedures, such as [[Endoscopy|endoscopies]] or [[Colonoscopy|colonoscopies]], are managed a technique called [[conscious sedation]] or [[Procedural sedation and analgesia|monitored anesthesia care]]. These cases are performed with regional anesthetics and a "twilight sleep" achieved through sedation with propofol and analgesics, and patients may remember perioperative events.<ref name=":0" /> When this technique is used, patients should be advised that this is management is distinct from general anesthesia to help combat any belief or fear that they were "awake" during anesthesia.<ref name=":0" />

==Intravenous reversal agents==
* [[Flumazenil]], reverses the effects of benzodiazepines
* [[Naloxone]], reverses the effects of opioids
* [[Neostigmine]], helps to reverse the effects of non-depolarizing muscle relaxants
* [[Sugammadex]], helps to reverse the effects of non-depolarizing muscle relaxants

== References ==
{{reflist}}

==External links==
* [https://www.bbc.co.uk/programmes/b00775zv Anaesthetics], BBC Radio 4 discussion with David Wilkinson, Stephanie Snow & Anne Hardy (''In Our Time'', Mar. 29, 2007)

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