Two factors make obtaining a detailed description of how these agents act difficult. The first is that volatile anesthetics, unlike most of the drugs used in medicine, bind only very weakly to their site s of action. As a result, high concentrations, often more than 1, times greater than for typical receptor- or protein-targeting drugs, are needed to achieve an anesthetic state.
This makes it tricky to obtain structural details of anesthetics bound in a specific manner to a protein.
It also affects the function of many proteins in nerve cell membranes, making it challenging to ascertain which of them are the key mediators of anesthetic action. A second problem is that volatile anesthetics tend to partition into lipids and exert their primary effects on synaptic neurotransmission by interacting with proteins in a lipid environment.
It is harder to gain detailed structural information for membrane proteins than it is for water-soluble proteins. Such structural data are essential for understanding how anesthetics interact with proteins and, more importantly, alter their function. Because of the lack of structural data for membrane proteins both in the presence and absence of anesthetics, it remains unclear whether anesthetics exert their primary effects by direct interaction with these proteins, or indirectly via interaction with the lipids surrounding them.
Despite these limitations, researchers are taking advantage of a variety of methods to better discern how anesthetic agents induce an anesthetic "state" at the molecular level. The term state is in quotes, because a wide variety of agents--ranging from single atoms such as xenon to polycyclic hydrocarbons--can produce insensibility to pain and loss of awareness.
The molecular targets for these different agents do not appear to be the same. Thus the notion that there is a single molecular mechanism of action for all anesthetic agents is probably an oversimplification. Genetic tools are providing promising results regarding the molecular mechanism of anesthetic action. For example, researchers can alter specific protein function and then determine whether this protein can be linked to sensitivity or resistance to anesthetic action in lower organisms.
Many anaesthetics are thought to work by making it harder for neurons to fire, but this can have different effects on brain function, depending on which neurons are being blocked.
So brain-imaging techniques such as functional MRI scanning, which tracks changes in blood flow to different areas of the brain, are being used to see which regions of the brain are affected by anaesthetics.
Such studies have been successful in revealing several areas that are deactivated by most anaesthetics. Unfortunately, so many regions have been implicated it is hard to know which, if any, are the root cause of loss of consciousness.
Not according to a leading theory of consciousness that has gained ground in the past decade, which states that consciousness is a more widely distributed phenomenon.
We only become conscious of the experience if these signals are broadcast to a network of neurons spread through the brain, which then start firing in synchrony. This has shown that as consciousness fades there is a loss of synchrony between different areas of the cortex — the outermost layer of the brain important in attention, awareness, thought and memory Science , vol , p This process has also been visualised using fMRI scans.
A team led by Andreas Engel at the University Medical Center in Hamburg, Germany, have been investigating this process in still more detail by watching the transition to unconsciousness in slow motion. Normally it takes about 10 seconds to fall asleep after a propofol injection.
Engel has slowed it down to many minutes by starting with just a small dose, then increasing it in seven stages. We know that upon entering the brain, sensory stimuli first activate a region called the primary sensory cortex, which runs like a headband from ear to ear.
Then further networks are activated, including frontal regions involved in controlling behaviour, and temporal regions towards the base of the brain that are important for memory storage. Engel found that at the deepest levels of anaesthesia, the primary sensory cortex was the only region to respond to the electric shock. What could be causing the blockage? Engel has unpublished EEG data suggesting that propofol interferes with communication between the primary sensory cortex and other brain regions by causing abnormally strong synchrony between them.
The communication between the different regions of the cortex is not just one way; there is both forward and backward signalling between the different areas. EEG studies on anaesthetised animals suggest it is the backwards signal between these areas that is lost when they are knocked out.
Both propofol and the inhaled anaesthetic sevoflurane inhibited the transmission of feedback signals from the frontal cortex in anaesthetised surgical patients. Similar findings are coming in from studies of people in a coma or persistent vegetative state PVS , who may open their eyes in a sleep-wake cycle, although remain unresponsive.
Laureys, for example, has seen a similar breakdown in communication between different cortical areas in people in a coma. Many believe that studying anaesthesia will shed light on disorders of consciousness such as coma. Owen and others have previously shown that people in a PVS respond to speech with electrical activity in their brain. To learn more about Healthwise, visit Healthwise.
Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated. Updated visitor guidelines. You are here Home » General Anesthesia. Top of the page. Topic Overview General anesthesia is a combination of medicines that you inhale or receive through a needle in a vein to cause you to become unconscious.
Risks and complications from general anesthesia Serious side effects of general anesthesia are uncommon in people who are otherwise healthy. Rare but serious risks of general anesthesia include: Heart attack, heart failure, or stroke. Increases or decreases in blood pressure. Pneumonia or other breathing disorders.
Reactions to medicines used in the anesthesia. Muscle damage and a rapid increase in body temperature. Related Information Anesthesia. Credits Current as of: May 27, Top of the page Next Section: Related Information. Previous Section: Related Information Top of the page.
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