General anaesthetic
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A general anaesthetic drug is an anaesthetic (or anesthetic AE) drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthetist (BE) (or anesthesiologist AE) in order to induce or maintain general anaesthesia to facilitate surgery.
Drugs given to induce or maintain general anaesthesia are either given as:
- gases or vapors (inhalation anaesthetics) or
- injections (intravenous anaesthetics).
Most commonly these two forms are combined, although it is possible to deliver anaesthesia solely by inhalation or injection.
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 and sevoflurane are the most widely used volatile anaesthetics today. They are often combined with nitrous oxide. Older, less popular, volatile anesthetics, include isoflurane, halothane, enflurane, and methoxyflurane. Researchers are also actively exploring the use of xenon as an anaesthetic.
Injection anaesthetics are used for induction and maintenance of a state of unconsciousness. Anaesthetists prefer to use intravenous injections as they are faster, 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, and
- ketamine.
Mechanism of action
Researchers agree that ion channels are the ultimate site of action of general anaesthetics, and are now determining the exact molecular mechanisms. However, the sites of action of general anaesthetics proved difficult to identify until the last decade. The wide variation in structure, ranging from complex steroids to the inert monatomic gas xenon, led to several now outdated theories of anaesthetic action.
It is now known that general anaesthetics act on the central nervous system by modifying the electrical activity of neurons at a molecular level by modifying the function of ion channels. This may occur by anaesthetic molecules binding directly to ion channels or by their disrupting the function of molecules that maintain ion channels.
Scientists have cloned forms of receptors in the past decade, adding greatly to knowledge of the proteins involved in neuronal excitability. These include:
- voltage-gated ion channels, such as sodium, potassium, and calcium channels
- the ligand-gated ion channel superfamily and
- the G protein-coupled receptor superfamily.