ADVERTISEMENTS:
This article throws light upon the seven main theories of general anaesthesia. The theories are: 1. Lipid Theory 2. Surface Tension Theory (Adsorption Theory) 3. Cell Permeability Theory 4. Neuro Physiological Theory 5. Colloidal Theory 6. Physical Theory 7. Biochemical Theories.
1. Lipid Theory:
This theory was advanced by Meyer (1899,1901) and Overton (1901). This theory propose that there is direct relationship between the affinity of an anaesthetic to lipids and its depressant action. Nerve cell and membranes contains lipids. Anaesthetic is thought to gain access to nerve tissue by virtue of its lipid solubility.
Solubility in Fat/Solubility of Water = Partition Coefficient
ADVERTISEMENTS:
Higher the partition-coefficient, higher is the potency of anesthetics. In other words, higher solubility in fat and lesser in water-more the potency. Wider variety of inhalation anaesthetic, obey this rule.
Phallacies:
(i) These substances were examined in-vitro with vegetable oils rather than with brain lipids and body fluids.
(ii) Alkaloids and many inorganic ions do not comply with the theory.
ADVERTISEMENTS:
(iii) Many lipid soluble substances are not anesthetic rather they produce convulsion.
(iv) It is now known that anaesthetics interact with proteins.
(v) Finally, above proposal explains only in transport of anaesthetic to cells of central nervous system and not the mechanism of narcosis.
2. Surface Tension Theory (Adsorption Theory):
Trambe (1904) and Lillie (1909) proposed the anaesthetic potency of the lower surface tension. Warburg (1921, 1930) proposed that the accumulation of narcotic agents on the cell surface caused alteration of metabolic processes, permeability and neural transmission resulting into anaesthesia.
Elements and Wilson (1962) demonstrated that the nitrous oxide (N2O), cyclopropane, halothane and chloroform lower the surface tension at a fat water interface.
3. Cell Permeability Theory:
Hober (1907), Lillie (1909), Loewe (1913) and Winter Stein (1926) proposed that anaesthetics cause a change in permeability of the cell of CNS. Change in permeability interferes with the ionic movements necessary for membrane depolarization. Shanes (1958) reported that certain agents may physically stabilises the cell membrane by preventing increase in all permeability.
Anaesthetic agents penetrate cell membrane and physically limit cell permeability and thus stabilises against depolarization (ether, chloroform and urethane). Diethyl ether selectively decreases the permeability to sodium ions.
Many other inhalation agents have been shown to influence sodium ions across the toad bladder and frog skin. Increase in R.B.C. permeability to glucose by carbon dioxide (CO2) is inhibited by halothane. However, whether these changes cause anaesthesia and indeed, how these changes are produced remains unexplained.
4. Neuro Physiological Theory:
Chloroform, ether and barbiturates have been shown to inhibit synaptic transmission in cat superior cervical ganglion and at the same time inhibit axonal conduction. It has been postulated that anaesthetics inhibit ascending reticular formation which is important in maintenance of consciousness.
ADVERTISEMENTS:
ADVERTISEMENTS:
Some anaesthetics such as cyclopropane have profound effect on diffuse thalamic projection system in brain while the subject remains quite aware of external stimuli. Thus, the theory gives important information regarding the neural effects of anaesthetics but does not propose a basic fundamental mechanisms by which agents produce these effects.
5. Colloidal Theory:
This theory was initially proposed by Claud Bernard (1875) and collaborated by Bancroft and Ritcher (1931). This theory propose that aggregation of colloids in cells accompanies anaesthesia reversibly and thereby allowing for recovery.
This was derived from putting muscle tissue in chloroform on a result there was increased optical density of muscle tissue. Diethyl ether and halothane inhibit movement of protoplasmic streaming.
6. Physical Theory:
ADVERTISEMENTS:
Attempts have been made to relate anaesthetic potency with thermodynamic activity or the molecular size of the agent. Increased potency has been correlated with increased magnitude of the vander waal forces that relate to molecular volume and at reaction between molecules.
Pauling Theory:
Pauling (1961-64) proposed that anaesthetic agents can form hydrated microcrystals or clathrates with the CNS. This involves an interaction of molecules of anaesthetics with water molecules in brain, rather than with lipids.
The formation of clathrates mainly in synaptic regions increase the impedance of the encephalonic network of conductors. Since, the clathrates are not stable at body temperature or atmospheric pressure, he postulated that they are stabilized by the charged side chains of proteins or CNS solutes.
ADVERTISEMENTS:
Miller Theory:
Miller (1961) pointed that anaesthetic agent within CNS is able to orient water molecules around it similar to Pauling’s microcrystals but of smaller size and paradoxically termed it an “ice-berg”. He postulated that gas filled ice-berg functioned to decrease electrical conductance, stiffen the lipid or other materials within the membrane and plugs the pores of membranes.
These approaches remain attractive but unproven because:
(i) Hydrated microcrystals formation take place at lower temperatures, but experimental evidence is lacking as to its formation during anaesthesia.
ADVERTISEMENTS:
(ii) Hydrate dissociation pressure does not furnish the best correlation with anaesthetic potency.
(iii) It is not possible to prepare hydrates of all anaesthetics in-vitro.
7. Biochemical Theories:
Various workers have sought to explain anaesthesia in terms of biochemical phenomena. It explains that anaesthetic drugs act by modifying or interfering with process of synthesis, storage, release, action, metabolism of one or more of the neurotransmitter agents.
Uncoupling phosphorylation explains the mechanism of action of barbiturates and states that there is decreased synthesis of ATP due to inhibition of oxidative phosphorylation process or enzymes by the anaesthetic drugs. The anaesthetic agents may inhibit the normal activity of one or more of the enzymes of CNS involved in the synthesis of certain neurotransmitter agents.
