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.
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
Drugs given to induce general anaesthesia can be 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.
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:
- 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
Intravenous general anesthetics
Intravenously-delivered general anesthetics are typically small and highly lipophilic molecules. These characteristics facilitate their rapid preferential distribution into the brain and spinal cord, which are both highly vascularized and lipophilic. It is here where the actions of these drugs lead to general anesthesia induction.
Following distribution into the central nervous system (CNS), the anesthetic drug then diffuses out of the CNS into the muscles and viscera, followed by adipose tissues. In patients given a single injection of drug, this redistribution results in termination of general anesthesia. Therefore, following administration of a single anesthetic bolus, duration of drug effect is dependent solely upon the redistribution kinetics.
The half-life of an anesthetic drug following a prolonged infusion, however, depends upon both drug redistribution kinetics, drug metabolism in the liver, and existing drug concentration in fat. When large quantities of an anesthetic drug have already been dissolved in the body's fat stores, this can slow its redistribution out of the brain and spinal cord, prolonging its CNS effects. For this reason, the half-lives of these infused drugs are said to be context-dependent. Generally, prolonged anesthetic drug infusions result in longer drug half-lives, slowed elimination from the brain and spinal cord, and delayed termination of general anesthesi
Inhalational general anesthetics
Minimal alveolar concentration (MAC) is the concentration of an inhalational anesthetic in the lungs that prevents 50% of patients from responding to surgical incision. This value is used to compare the potencies of various inhalational general anesthetics and impacts the partial-pressure of the drug utilized by healthcare providers during general anesthesia induction and/or maintenance.
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