 Hello everyone welcome back to another session in dentistry and more. So we are continuing local anesthesia part 4. So this session is about classification and the concept of dissociation of local anesthetic and the most important Hansen-Hasselbach equation. Okay so let's start with the classification. So the first classification category is biological site and mode of action. So biological site of action. So in this category we have A, B, C, D. So the class A. So agents acting at receptor sites on external surface of nerve membrane. So this is acting on the external surface. So the most common example is biotoxins. So which is acting on the external surface. So the class B, okay so this is class A, class B, class C and class D. So in class B so it is the acting agents which is acting on receptor sites on internal surface of nerve membrane, internal surface. Example is lidocaine and scorpion, corpion venom, lidocaine. Lidocaine is quaternary ammonium analogues of lidocaine whereas class C. So the agents acting by receptor independent of physiochemical mechanism which is benzo okay which is the receptor independent of physiochemical mechanism and class D agents acting by combination of receptors and receptor independent mechanism. So most common examples are the lidocaine, prilocaine and mypivocaine. So here also we have one lidocaine that is nothing but quaternary ammonium analogues. So this is class A, B, C, D based on the biological site and mode of action. Next we have based on the source. So from where it is obtained that is natural, synthetic and others okay. Next based on the mode of application can be topical or injectable. Next based on the duration of action. So ultra short that is very, very lesser duration then short then medium and long. So based on the onset of action short we have intermediate long. So that's all about classification now let's see what is dissociation of local anesthetics. So local anesthetics are available as salts usually hydro chlorides for clinical use. Also the salts both water soluble and stable is dissolved in either sterile water or saline. So in this solution it exists simultaneously as unchanged molecule. So this is an unchanged molecule without any charge which is called as base and positively charged molecule which is known as cations. So this is the equation. So the relative concentration of each ionic form in the solution varies in the pH of the solution or surrounding tissues. So in the presence of high concentration of hydrogen ion that is low pH we have very high concentration of hydrogen ions. So what happens is the equilibrium shifts to left and most of the anesthetic solution exists in cationic form. So this will become there will be shifting equilibrium shifting to left okay. Whereas the hydrogen ion concentration decreases that is a higher pH when this is decreases that means high pH. The equilibrium shift towards a free base form that is more number of free base form will be available. So that is depending upon the pH. So when there is a low pH the more of cationic form will be present when there is high pH more of base form will be available. So the relative proportion of this ionic form also depends on the dissociation constant which is known as dissociation, dissociation constant that is pKa. So this pKa is nothing but measure of molecules affinity for H plus ions what is the affinity towards H plus ions is what meant by pKa. So when the pH of the solution has the same value as pKa of local anesthetics exactly half of the drug will exist as RNH plus and the other half will be in RN form okay. So this RNH will be equal to RN that is when pH of the solution pH of the solution has the same value as pKa of the local anesthetic. So this ionic form will be equal to as base form when pH is equal to pKa of that is the dissociation constant of local anesthetic. So the percentage of drug exist in either form can be determined. So in which form the drug or percentage of drug existing in the solution can be determined by an equation which is known as Handterson-Hasselbach equation okay. So this equation actually determines how much of a local anesthetic will be in a non-ionized versus ionized form based on the tissue pH and the pKa of local anesthetic. So the injectable local anesthetics are weak bases. So injectable local anesthetic weak bases though dissociation constant will be around 7.5 to 9.5. So when a local anesthetic is injected into tissues it is neutralized and part of the ionized form is converted to non-ionized. So part of the ionized form will be converted to non-ionized and this non-ionized base this is what diffused into the nerve. So this is what diffused into the nerve okay. So when we inject the local anesthetics into the tissues it is neutralized and part of the ionized form is converted to non-ionized form and the non-ionized base is what diffuses into nerve. So hence if the tissue is infected. So many cases we might face a patient has infection okay in that case why the LA is not working properly because when the tissue is infected the pH is lower the pH is very low because it is more acidic because it has infection. So according to this equation there will be less of the non-ionized form okay the presence of this non-ionized form will be very less when there is an infection. So this RN is very less to cross the nerve membrane okay. So now the less number of non-ionized form of local anesthetic tract to cross into the nerve membrane so the LA will be less effective. So that is why in acidic condition or in infection cases the LA will not work that is the reason because if the infection is there it will be more acidic the pH is very low and as per the equation there will be very less amount of non-ionized form to cross the nerve membrane. So this is what actually crossing the nerve membrane. So less number of RN for the base form to cross the membrane that will be less effective. So next part is mechanism of action of local anesthetic LA mechanism okay. So we already learned it. So LA mechanism so these are the sequence the first thing is displacement of calcium ion from the sodium channel receptor site. So we have this receptor site okay. So this is a receptor site receptor site this is sodium channel sodium channel. So what happens is the calcium ion is displaced from sodium channel receptor site. So calcium ions will be displaced from this receptor site. So the binding of local anesthetic molecule to this receptor site. So the our RN molecule will be binding here. First thing is calcium displacement then the RN molecule the local anesthetic molecule binds to the receptor site. So it blocks the sodium channel. So what it does is it blocks the sodium channel okay. So that is the ultimate aim. So once the sodium enters there will be depolarization but we want repolarization. So there will be decrease sodium conductance. So it depress the rate of electrical depolarization and there will be failure to achieve the threshold potential level because there is no sodium going inside and lack of propagated action potential and there will be conduction blockade conduction blockade. So this is what is happening okay. So from receptor site calcium will be displaced the LA molecule will be attached to this receptor site the sodium channel the conduct the conduction will be reduced the sodium channel will be blocked and there will be decrease sodium conductance decrease rate of electrical depolarization and failure to achieve threshold potential level and lack of development of propagated action potential. So that is what is happening the sodium ion channel is blocked in pain neurons okay. So that is all about this session. So we discussed the classification of local anaesthesia then about the dissociation how the LA molecule is changing from cation to base form and the famous equation and finally the mechanism how the LA molecules blocks the sodium channel. So I will come up with another topic in all surgery thank you.