General anaesthetic
A general anaesthetic (or anesthetic, see spelling differences) drug is an anaesthetic drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anesthesia provider in order to induce or maintain general anaesthesia to facilitate surgery.
Mode of administration
Drugs given to induce or maintain general anaesthesia are either given as:
- Gases or vapors (inhalational anaesthetics)
- 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 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 vaporized 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 anesthetics, include halothane, enflurane, and methoxyflurane. Researchers are also actively exploring the use of xenon 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 or subcutaneous injections. Among the most widely used drugs are:
- Propofol
- Etomidate
- Barbiturates such as methohexital and thiopentone/thiopental
- Benzodiazepines such as midazolam and diazepam
- Ketamine is used in the UK as "field anaesthesia", for instance at a road traffic incident, 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).
Method of Action
Lipid theory
Overton and Meyer postulated that 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. [1]
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.[2]
Ion Channels
General anaesthetics inhibit excitatory functions of some CNS receptors, such as glutamate or 5-HT 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.
General anaesthetics may decrease transmitter release pre-synptically or decrease excitability of post-synaptic neuron.
Pharmacokinetics
Induction
The arterial concentration and therefore the induction/recovery phase is governed by numerous factors, including:
- blood:gas partition co-efficient
- inspired air concentrations
- breathing rate
The potency of the drug is governed by the oil:gas partition coefficient, which also influences distribution. High oil:gas coefficients cause quick redistribution into adipose tissue, at the expense of CNS anaesthetic action. It is this redistribution phase into fat which causes the recovery of consciousness. This is why the weight and fat ratio of a patient must be considered when administering. Multiple administrations cause a big rise in concentrations in adipose tissue to maintain the same arterial concentration. In the terminal phase of multiple doses the recovery will take a very long time.
Three redistribution phases exist:
- Fast redistribution phase: drug diffuses into low blood flow tissues
- Intermediate phase:diffusion out of lean tissues and into adipose tissue
- Terminal phase: complete elimination from all tissue.
Elimination
Volatile anaesthetics are eliminated in the terminal phase via the lungs. A low blood:gas coefficient is therefore necessary for quick removal of anaesthetic. When oil:water coefficient is high, there will be little anaesthetic in the blood, so elimination will be slow, giving a prolonged hangover effect.
Some are drugs are metabolised by the liver, and their metabolites are often toxic (e.g. chloroform)
See also
Notes
- ^ Anesthesia UK, http://www.frca.co.uk/article.aspx?articleid=100341, `15 May 08
- ^ The Window that Is Opened by Optical Isomers, I Ueda, Anesthesiology. 90(1):336, January 1999.
- Pharmacology, Rang and Dale, Churchill Livingstone; 6 edition (January 25, 2007), 0443069115