Endogenous anesthetic

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Endogenous anesthetics are analogs of anesthetics the body makes that have the properties and similar mode of action of general anesthetics. [1]

Contents

Types of endogenous anesthetics

Carbon dioxide

Carbon dioxide (CO2) is an abundant gas produced as the final product of glucose metabolism in animals. CO2 anesthesia is most frequently used for anesthetizing flies. [2] But it has also been considered as a fast acting anesthetic in small laboratory animals. [3]

In the 1900s, CO2 anesthesia, known as CO2 therapy was used by psychiatrists for the treatment of anxiety. The patients would receive 70% CO2 in combination with 30% oxygen causing rapid and reversible loss of continuousness. [4]

Ammonia

Ammonia has also been shown to have anesthetic properties. [5]

Mechanism of action

The most abundant endogenous anesthetics are small hydrophobic gaseous metabolites of catabolism and likely work through a membrane-mediated mechanism of general anesthesia.

In the 1800s anoxia was considered the mechanism of CO2 anesthesia. [6] However, studies in humans showed the opposite, oxygenation of the brain tissue increases with increase CO2 in the lung. [7] More recent studies have shown in bees that anoxia is also not the mechanism. [8]

In humans, CO2 raises the threshold of stimulation of the nerve cell, decreases the speed of conduction of impulses along the nerve, and increases the height and prolonged duration of the action potential. [9]

While the endogenous anesthetics appear to have a similar mechanism of action to inhaled anesthetics, their rapid endogenous metabolism complicates their use in humans. Apart from flies, exogenous compounds have proven more useful for maintaining general anesthesia.

History

The first private demonstration of an anesthetic was carbon dioxide by Henry Hill Hickman in a dog cerca 1823.

Related Research Articles

General anaesthetics 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 encompass multiple biological targets involved in the control of neuronal pathways. The precise workings are the subject of some debate and ongoing research.

<span class="mw-page-title-main">Nitrogen narcosis</span> Reversible narcotic effects of respiratory nitrogen at elevated partial pressures

Narcosis while diving is a reversible alteration in consciousness that occurs while diving at depth. It is caused by the anesthetic effect of certain gases at high pressure. The Greek word νάρκωσις (narkōsis), "the act of making numb", is derived from νάρκη (narkē), "numbness, torpor", a term used by Homer and Hippocrates. Narcosis produces a state similar to drunkenness, or nitrous oxide inhalation. It can occur during shallow dives, but does not usually become noticeable at depths less than 30 metres (98 ft).

<span class="mw-page-title-main">Sodium thiopental</span> Barbiturate general anesthetic

Sodium thiopental, also known as Sodium Pentothal, thiopental, thiopentone, or Trapanal, is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog of pentobarbital, and an analog of thiobarbital. Sodium thiopental was a core medicine in the World Health Organization's List of Essential Medicines, but was supplanted by propofol. Despite this, thiopental is listed as an acceptable alternative to propofol, depending on local availability and cost of these agents. It was previously the first of three drugs administered during most lethal injections in the United States, but the US manufacturer Hospira stopped manufacturing the drug in 2011 and the European Union banned the export of the drug for this purpose. Although thiopental abuse carries a dependency risk, its recreational use is rare.

<span class="mw-page-title-main">Lidocaine</span> Local anesthetic

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, lidocaine typically begins working within several minutes and lasts for half an hour to three hours. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area. It is often used mixed with a small amount of adrenaline (epinephrine) to prolong its local effects and to decrease bleeding.

<span class="mw-page-title-main">Sevoflurane</span> Inhalational anaesthetic

Sevoflurane, sold under the brand name Sevorane, among others, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. After desflurane, it is the volatile anesthetic with the fastest onset. While its offset may be faster than agents other than desflurane in a few circumstances, its offset is more often similar to that of the much older agent isoflurane. While sevoflurane is only half as soluble as isoflurane in blood, the tissue blood partition coefficients of isoflurane and sevoflurane are quite similar. For example, in the muscle group: isoflurane 2.62 vs. sevoflurane 2.57. In the fat group: isoflurane 52 vs. sevoflurane 50. As a result, the longer the case, the more similar will be the emergence times for sevoflurane and isoflurane.

<span class="mw-page-title-main">General anaesthesia</span> Medically induced loss of consciousness

General anaesthesia (UK) or general anesthesia (US) is a method of medically inducing loss of consciousness that renders a patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general anaesthetic medications, which often act in combination with an analgesic and neuromuscular blocking agent. Spontaneous ventilation is often inadequate during the procedure and intervention is often necessary to protect the airway. General anaesthesia is generally performed in an operating theater to allow surgical procedures that would otherwise be intolerably painful for a patient, or in an intensive care unit or emergency department to facilitate endotracheal intubation and mechanical ventilation in critically ill patients.

In physiology, respiration is the movement of oxygen from the outside environment to the cells within tissues, and the removal of carbon dioxide in the opposite direction that's to the environment.

<span class="mw-page-title-main">Hypercapnia</span> Abnormally high tissue carbon dioxide levels

Hypercapnia (from the Greek hyper = "above" or "too much" and kapnos = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous product of the body's metabolism and is normally expelled through the lungs. Carbon dioxide may accumulate in any condition that causes hypoventilation, a reduction of alveolar ventilation (the clearance of air from the small sacs of the lung where gas exchange takes place) as well as resulting from inhalation of CO2. Inability of the lungs to clear carbon dioxide, or inhalation of elevated levels of CO2, leads to respiratory acidosis. Eventually the body compensates for the raised acidity by retaining alkali in the kidneys, a process known as "metabolic compensation".

<span class="mw-page-title-main">Soda lime</span> Chemical mixture

Soda lime, a mixture of sodium hydroxide (NaOH) and calcium oxide (CaO), is used in granular form within enclosed breathing environments like general anesthesia and its breathing circuit, submarines, rebreathers, and recompression chambers. Its purpose is to eliminate carbon dioxide from breathing gases, preventing carbon dioxide retention and, eventually, carbon dioxide poisoning. The creation of soda lime involves treating slaked lime with a concentrated sodium hydroxide solution.

The control of ventilation is the physiological mechanisms involved in the control of breathing, which is the movement of air into and out of the lungs. Ventilation facilitates respiration. Respiration refers to the utilization of oxygen and balancing of carbon dioxide by the body as a whole, or by individual cells in cellular respiration.

<span class="mw-page-title-main">Theories of general anaesthetic action</span> How drugs induce reversible suppression of consciousness

A general anaesthetic is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthetist/anesthesiologist to induce or maintain general anaesthesia to facilitate surgery.

<span class="mw-page-title-main">Desflurane</span> Chemical compound

Desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether) is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane, and isoflurane, it is a racemic mixture of (R) and (S) optical isomers (enantiomers). Together with sevoflurane, it is gradually replacing isoflurane for human use, except in economically undeveloped areas, where its high cost precludes its use. It has the most rapid onset and offset of the volatile anesthetic drugs used for general anesthesia due to its low solubility in blood.

<span class="mw-page-title-main">Inhalational anesthetic</span> Volatile or gaseous anesthetic compound delivered by inhalation

An inhalational anesthetic is a chemical compound possessing general anesthetic properties that is delivered via inhalation. They are administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vaporiser and an anesthetic delivery system. Agents of significant contemporary clinical interest include volatile anesthetic agents such as isoflurane, sevoflurane and desflurane, as well as certain anesthetic gases such as nitrous oxide and xenon.

Inert gas asphyxiation is a form of asphyxiation which results from breathing a physiologically inert gas in the absence of oxygen, or a low amount of oxygen, rather than atmospheric air. Examples of physiologically inert gases, which have caused accidental or deliberate death by this mechanism, are argon, helium, nitrogen and methane. The term "physiologically inert" is used to indicate a gas which has no toxic or anesthetic properties and does not act upon the heart or hemoglobin. Instead, the gas acts as a simple diluent to reduce the oxygen concentration in inspired gas and blood to dangerously low levels, thereby eventually depriving all cells in the body of oxygen.

<span class="mw-page-title-main">Methoxyflurane</span> Chemical compound

Methoxyflurane, sold under the brand name Penthrox among others, is an inhaled medication primarily used to reduce pain following trauma. It may also be used for short episodes of pain as a result of medical procedures. Onset of pain relief is rapid and of a short duration. Use is only recommended with direct medical supervision.

The Fink effect, also known as "diffusion anoxia", "diffusion hypoxia", or the "second gas effect", is a factor that influences the pO2 (partial pressure of oxygen) within the pulmonary alveoli. When water-soluble gases such as anesthetic agent N2O (nitrous oxide) are breathed in large quantities they can be dissolved in body fluids rapidly. This leads to a temporary increase in both the concentrations and partial pressures of oxygen and carbon dioxide in the alveoli.

<span class="mw-page-title-main">Flurothyl</span> Chemical compound

Flurothyl (Indoklon) is a volatile liquid drug from the halogenated ether family, related to inhaled anaesthetic agents such as diethyl ether, but having the opposite effects, acting as a stimulant and convulsant. A clear and stable liquid, it has a mild ethereal odor whose vapors are non-flammable. It is excreted from the body by the lungs in an unchanged state.

Equivalent narcotic depth (END) (historically also equivalent nitrogen depth) is used in technical diving as a way of estimating the narcotic effect of a breathing gas mixture, such as nitrox, heliox or trimix. The method is used, for a given breathing gas mix and dive depth, to calculate the equivalent depth which would produce about the same narcotic effect when breathing air.

In some individuals, the effect of oxygen on chronic obstructive pulmonary disease is to cause increased carbon dioxide retention,

Gaseous signaling molecules are gaseous molecules that are either synthesized internally (endogenously) in the organism, tissue or cell or are received by the organism, tissue or cell from outside and that are used to transmit chemical signals which induce certain physiological or biochemical changes in the organism, tissue or cell. The term is applied to, for example, oxygen, carbon dioxide, sulfur dioxide, nitrous oxide, hydrogen cyanide, ammonia, methane, hydrogen, ethylene, etc.

References

  1. Lerner, Richard A. (9 December 1997). "A hypothesis about the endogenous analogue of general anesthesia". Proceedings of the National Academy of Sciences. 94 (25): 13375–13377. doi:10.1073/pnas.94.25.13375. PMC   33784 .
  2. Nilson, Theresa L.; Sinclair, Brent J.; Roberts, Stephen P. (October 2006). "The effects of carbon dioxide anesthesia and anoxia on rapid cold-hardening and chill coma recovery in Drosophila melanogaster". Journal of Insect Physiology. 52 (10): 1027–1033. doi:10.1016/j.jinsphys.2006.07.001. PMC   2048540 .
  3. Kohler, I.; Meier, R.; Busato, A; Neiger-Aeschbacher, G.; Schatzmann, U. (1 April 1999). "Is carbon dioxide (CO2) a useful short acting anaesthetic for small laboratory animals?". Laboratory Animals. 33 (2): 155–161. doi:10.1258/002367799780578390.
  4. LAVERNE, AA (May 1953). "Rapid coma technique of carbon dioxide inhalation therapy". Diseases of the nervous system. 14 (5): 141–4. PMID   13052042.
  5. Brosnan, Robert J.; Yang, Liya; Milutinovic, Pavle S.; Zhao, Jing; Laster, Michael J.; Eger, Edmond I.; Sonner, James M. (June 2007). "Ammonia Has Anesthetic Properties". Anesthesia & Analgesia. 104 (6): 1430–1433. doi: 10.1213/01.ane.0000264072.97705.0f .
  6. Antiquack (1826). "Surgical Humbug". The Lancet. 5 (127): 646.
  7. Moriarty, John D. (April 1954). "EVALUATION OF CARBON DIOXIDE INHALATION THERAPY". American Journal of Psychiatry. 110 (10): 765–769. doi:10.1176/ajp.110.10.765.
  8. Cressman, Anna; Amsalem, Etya (1 January 2023). "Impacts and mechanisms of CO2 narcosis in bumble bees: narcosis depends on dose, caste and mating status and is not induced by anoxia". Journal of Experimental Biology. 226 (1). doi: 10.1242/jeb.244746 .
  9. Moriarty, John D. (April 1954). "EVALUATION OF CARBON DIOXIDE INHALATION THERAPY". American Journal of Psychiatry. 110 (10): 765–769. doi:10.1176/ajp.110.10.765.