 Hello everyone, welcome back to another session in Tentistry and more so we are continuing our local anesthesia sessions So this session is about theories of mechanism of action of local anesthetics So there are various theories Which has been put forward over the years to explain the mechanism of action of local anesthetics The first one was acetylcholine theory acetylcholine theory Which stated that acetylcholine was involved in nerve conduction in addition to its role as a neurotransmitter at nerve synapses So it is basically a nerve synapse neurotransmitter, but it has got Role in local anesthesia That is what this theory is saying But there is no scientific evidence To prove that acetylcholine is involved in neural transmission. So it was a rejected in its first place so So the second theory was calcium displacement theory So this theory states that the nerve block or local anesthetic nerve block was produced by Displacement of calcium from some membrane site, which controlled permeability of sodium. So sodium is the key element Which is involved in local anesthesia because we have seen in our last session how sodium is involved in depolarization and repolarization. So when the sodium enters to cell membrane the depolarization starts So sodium is a key element. So calcium displacement theory highlighting the involvement of sodium And next theory we have surface charge repulsion theory surface charge Repulsion theory So it says that local anesthetics acted by binding to nerve membrane and changing the electric Potential at the membrane surface. So if you have the nerve membrane, so it has post-team outside and Negative inside, okay So let it be the outside and this be the inside so negative charge is inside and post-team charge on outside So this local anesthetics will bind to the nerve membrane and changing the electrical Potential at the membrane surface. So the cationic Membrane cationic molecules that is the cationic drug molecules align at the membrane water interface Okay So we have this LMM Post-team charges, which is aligned here so Since the cationic drug molecules aligned at the membrane interface So some of the local anesthetic molecule carried a net post-team charge They made the electrical potential at the membrane surface more positive. So what happens? When it become more positive, it decreases the excitability of nerve by increasing the threshold potential So when we have more Positive charge here, it increases the threshold Potential that means The action potential needs more depolarization potential So it will be in that repolarization phase But the problem is there is no such evidence which indicate that resting potential of nerve membrane Is affected by LA molecules. So this theory was rejected. Okay So there is no concept Scientific evidence says that there is changing in threshold potential by the LA molecules So it was not accepted one Where as a fourth one is membrane expansion theory membrane Expansion theory Membrane expansion theory it states that local anesthetic molecule diffuse to Hydrophobic regions of membranes And produce a disturbance in the bulk membrane structure and expand the membrane and preventing Increasing the permeability to sodium ions. This is the membrane So what happens is? There is the LA molecules enters and this will be changed to Different shape. Okay, or it expands so it prevents Increasing permeability to sodium ions. So lipid soluble LA solutions can easily penetrate Through the lipid portions of cell membrane Changing the configuration of this lipoprotein matrix of nerve membrane Which results in decreased diameter of sodium channels. So, you know, we have channels sodium channels. We have learned in our first session Sodium channels where sodium enters to the cell membrane and causes depolarization. So sometimes As per this membrane expansion theory, it decreases the sodium channel diameter or it Expands the membrane and preventing an increase in permeability of sodium ions So ultimately There'll be inhibition of sodium conduction and thereby novel excitation So the ultimate aim is to Prevent the entry of sodium into nerve membrane. Okay, so that is the key thing when sodium enters to this What happens is there is depolarization So that is a membrane expansion theory And the most accepted theory is specific receptor theory. Okay So this is a entirely different mechanism Compared to all the four other theories. So this theory says that local anesthetics act by binding to specific receptors in the sodium channel. Okay, so we know what is sodium channel So sodium channel will be having a receptors a specific receptor where the local anesthetic molecules will get binded to So that is the mechanism, okay So not the acetylcholine or calcium displacement or surface charge or membrane expansion So this is a real mechanism how the LA works So there will be a receptors which is present on the sodium channel where the LA molecules get Attached to okay So it is not mediated by any change in the general properties of cell membrane But the action of drug is very direct not changing by membrane potential or expanding or anything that sort of This is direct action directly Attaching to this receptors which is on the sodium channel and doing the LA action So once it is attached to this there will be biochemical and electrophysiological changes happening And the mechanism is very simple once the molecule LA molecule is attached to the specific receptors The permeability to sodium ion is decreased Okay, so only when the sodium ions enters into the cell membrane the depolarization happens. So what we want is Repolarization the prolonged repolarization. We don't want depolarization. We just want Continuous repolarization state. So it is not letting the sodium ions to enter into this membrane. So The permeability to sodium ion is decreased or eliminated and the nerve conduction is interrupted. Okay So that is a mechanism. So this is the most acceptable one specific receptor theory So we learned This class was about the theories as a tail coil in calcium displacement surface charge membrane expansion And the most acceptable one that is specific receptor theory So hope you understood this concept of theories of local anesthesia mechanism So i'll come up with next topic. Uh, that is the properties or the components Of local anesthesia What are the components which is present in local anesthesia and its function So i'll come up with that topic. Uh, thank you