Theories of anaesthesia



Theories of anaesthesia

·         The mode of action of general anaesthetics has been studied for many decades but still there is no clear explanation regarding the mechanism of action.
·         Anaesthetics appear to act principally on the cell membrane; therefore, theories of anaesthesia focus primarily on the interaction of anaesthetics with two main membrane components namely lipids and proteins.

Lipid theory / Meyer and Overton theory
·         Meyer (1899) and Overton (1901) in separate studies identically postulated that anaesthetic potency varies with the lipid solubility of the drug.
·         The more lipid soluble a drug is, the greater its anaesthetic potency.
·         But it is now known that all highly lipid soluble substances are not anaesthetics and some potent anaesthetics are not lipid soluble.

Pauling and Miller theory / Hydrate theory
·         Pauling and Miller in 1961 postulated that when anaesthetic agents are administered, simple molecules like water may be linked together by hydrogen bonding to form ice- like cages / structures which are occupied by anaesthetic agents and form anaesthetic hydrate crystals (ice burgs) or calthrates.
·         These calthrates disturbs function of membrane proteins and also interfere with ionic movements.
·         It gives poorer correlation of anaesthetic potency with hydrate formation.

Membrane expansion theory
·         This theory postulates that anaesthetic molecules penetrate into hydrophobic region of the cell membrane and causes its expansion
·         Here, the mechanism of expansion has not been fully explained

Membrane fluidization theory
·         This theory postulates that anaesthetic agents by dissolving in the membrane lipids cause loosing or fluidization of lipid bilayer region of the membrane.
·         The increase in fluidity or disordering restricts the mobility of protein molecules surrounding the ionic channels, thereby impeding opening up of the ion channels
·         But this theory also fails to explain the mechanism of fluidization.

Biochemical theory
·         A number of biochemical theories have also been postulated and reviewed.
·         These include inhibition of glucose metabolism in brain cells, interference in ATP production, cellular respiration etc.,
·         But there are no conclusive evidence for such mechanisms occurs in the intact brain when general anaesthetics are administered.

Protein theory
·         There is increasing evidence that anaesthetics exert their effect probably by direct interactions with proteins at molecular levels, rather than by disturbing the matrix of lipid bilayer as postulated earlier.
·         Structural changes in protein conformation are induced by anaesthetic compounds results in altering receptor or channel function.
·         Eg: Many inhalation anaesthetics, barbiturates, benzodiazepines and Propofol potentiate action of the inhibitory neurotransmitter GABA at GABAA and GABAB receptor.

In summary, recent evidence tends to argue more in favour of a protein site.

Comments

Post a Comment

Popular posts from this blog

Skeletal muscle relaxants

Image
Skeletal muscle relaxants Physiology of SKM Contraction 1. Motor nerve impulse à 2. Release of ACh à 3. Binds with N M receptors at NMJ à 4. Depolarization & development of EPP at motor end plate (Mainly due to influx of Na + ) à 5. Muscle action potential (MAP) – contraction of SKM à 6. ACh is rapidly inactivated by ChE leading to repolarization à 7. Muscle is ready for a fresh nerve impulse. MECHANISM OF ACTION OF MUSCLE RELAXANTS Centrally acting muscle relaxants -           Reduce SKM tone by a selective action in the cerebrospinal axis, without altering consciousness. -           They selectively depress spinal and supraspinal polysynaptic reflexes involved in the regulation of muscle tone without significantly affecting monosynaptically mediated stretch reflex. -           Polysynaptic pathways in ascending reticula...
Read more

CNS Stimulants

CNS Stimulants The CNS stimulants are classified into three major categories a.        Cortical stimulants b.       Medullary stimulants c.        Spinal stimulants Cortical stimulants These are further divided into three types 1.        Classical cortical stimulants – Cocaine, Xanthines, Ephedrine and Amphetamine 2.        Psychotomimetics – Lysergic acid 3.        Antidepressants (Thymoleptics) – Imipramine , tranylcypramine and Isoniazid. Classical cortical stimulants ·          Cocaine, Amphetamine, Ephedrine and Xanthine are cortical stimulants. ·          These drugs affect mainly the sensory cortex but the motor cortex is also stimulated with high dose. Cocaine ·     ...
Read more

Pharmacokinetics - Drug absorption and Transport of drugs across biological membranes

Transport of drugs across biological membranes All pharmacokinetic processes involved transport of the drug across biological membranes. Biological Membrane Biological membranes may be viewed as mosaics of functional units composed of lipoprotein complex. Most membranes are composed of a fundamental structure called the unit membrane or plasma membrane. This boundary, which is 80 to 100 A° thick, surrounds single cell and nuclei. More complex barriers such as the intestinal epithelia and the skin are composed of multiples of this functional structure. The plasma membrane consists of a bilayer of amphipathic lipids with their hydrocarbon chains oriented inward to form a continuous hydrophobic phase and their hydrophilic heads oriented outward. Individual lipid molecules in the bilayer can move laterally, endowing the membrane with fluidity, flexibility, high electrical resistance and relative impermeability to highly polar molecules. The known fluidity of the phospholipids i...
Read more