Insulin preparations and classification

Various types of insulin preparations can be obtained from modification of amino acids in Human insulin particularly at B chain. In this vide we will discuss classification of insulin preparations based on their pharmacokinetics.

Hi everyone today in this video we are going to discuss about insulin preparations what are the different types of insulin preparations how they are modified in the amino acid sequence and what are their pharmacokinetic parameters we will discuss in this video first of all let us see the sites of modification within the human insulin structure now within this

Human insulin structure particularly the b chain is a one of good site for modification the c terminal of b chain consisting of 5 amino acids starting from 26 to the 30 so b 26 to b 30 is one good site of modification to produce various types of insulin preparations with different pharmacokinetic parameters because this site is not responsible for firm classical

Action of insulin so it can be safely modified to produce various insulin preparations with different onset and duration of action similarly another site of modification is on the a chain so a 20 amino acid can also be modified to produce few of the insulin preparations and third side of modification is on the b chain that is the b3 amino acid so all these are

The various sites of modification within the structure of human insulin but the main site of modification is falling at the c terminal of b chain which is from b 26 to b 30 so most of the insulin preparations are obtained by modification of amino acids at this site so now we have different types of insulin preparations such as glycine glue lysine dtmer lispro

Big glue deck aspart in this way we have so many types of insulin preparations but it is not an easy task to remember these drugs because all these preparations are not equal in their pharmacokinetics if you are short acting fewer rapid acting and fewer long-acting insulin preparations so we may be confused to remember these insulin preparations but still we can

Remember in easy way by carefully observing what is a modification within the insulin structure so now let us discuss one by one the different types of insulin preparations and what is their modification within the structure first let us discuss with the regular insulin this regular insulin is also called as short acting insulin so this is one of the limitation

Of this regular insulin which shows a short duration of action even onset of action is also 30 minutes so when this regular insulin is given by subcutaneous route at the site of injection the insulin can form hexamers these hexamers are not readily absorbed and they should be cleaved into monomers and dimers so after some time this is cleaved into monomers and

Dimers which are absorbed into the systemic circulation so it requires some time for absorption so there will be delay in the onset of action so one of the limitation of regular insulin is that this preparation should be given 30 minutes before the meal in order to show a better therapeutic action but this reduce the patient compliance because administration

Of insulin before the 30 minutes of mail is not always practically possible so when this insulin is administered just before the male it may not control the postprandial glucose which reduce its therapeutic efficacy in order to minimize this limitation different types of insulin preparations are going to be derived which are rapid acting and they can be given

Within five to 15 minutes before the male now the short acting insulin can be modified to produce rapid acting insulins intermediate acting insulins long-acting insulins and ultra-long-acting insulins first of all let’s see the rapid acting insulin preparations we have three types of insulin preparations insulin aspart insulin lispro and insulin glu lysine

Within the name we can easily identify what is the modification in the amino acid sequence the insulin aspect is derived from replacement of one of the amino acid with aspartic acid at b 28th position similarly in the list pro two amino acids are switched one is the lysine signal is the proline so it is obtained from switching of lysine and proline at 29 and 28

Positions and third one is the glue lysine here we can clearly absorb two amino acids glutamic acid and lysine in this insulin preparation two amino acids are modified so glutamic acid is added at the 28th position and lysine at third portion of the b chain where they replace the original amino acids so these are the three rapid acting insulin preparations so now

These rapid acting insulin preparations are having onset of action variable from 5 to 15 minutes so these preparations can be given just 5 to 15 minutes before the meal and the duration of action of these insulin preparations is variable from two to four hours so these preparations can reduce the postprandial glucose with better efficacy with less hypoglycemic

Effect compared with regular insulin so now it is the first one in the rapid acting insulins insulin as part so within the structure of insulin this is the 28th position within the b chain at this portion aspartic acid is going to be incorporated now aspartic acid can replace the proline at b-28 position to produce insulin aspart so this is a fast acting insulin

Preparation with onset of action within 5-15 minutes so just before the meal it can be given to control postprandial glucose levels second one is the insulin list pro this is obtained from modification of amino acid sequence at b 28 and 29 position at the b 28th position proline is present and 29th position lysine is present when their sequence is modified we

Can produce insulin less pro so these amino acids are switched at 28th and 29 position to produce insulin least pro third one is the insulin glue lysine in this insulin preparation we can observe two modifications one is at the 29th position and second one is at the third portion of the b chain at the 29th position glutamic acid is going to be replacing so glutamic

Acid can replace the lysine and the third portion lysine is going to replace aspartame so again this is a rapid acting insulin that can be given 5-15 minutes before the meal second one is the intermediate acting insulin preparations we have one of the insulin preparation nph insulin so here the letter n indicates neutral p indicates protomine and the letter h

Indicates the name of the scientist has a dawn so nbh insulin is an intermediate insulin preparation this is having an onset of action around two hours and the peak time can be observed from 4 to 12 hours duration of action is variable from 14 to 24 hours this can be obtained by modification of insulin suspension so here the zinc as well as protomine are going

To be added to the insulin now when these are going to be combined with insulin protomine can form a complex with insulin such that it can produce precipitation of insulin in fine structure and the ph of the solution is maintained at the neutral ph so that’s what is called as neutral protomine hazard on insulin preparation now when this insulin preparation is

Given by subcutaneous root at the side of injection it can form few of the crystals these crystals are not easily dissolved but from these crystals insulin is slowly released resulting in the intermediate duration of action third one is a long-acting insulin preparations we have two types of preparations insulin glycine and insulin dtma here the glycine can be

Remembered in easy way here gl indicates glycine orgin indicates arginine so two amino acids are going to be modified glycine and arginine that is the insulin glycine and this glycine cannot be confused with the glue lysine gluolysine is a rapid acting insulin and glycine is a long-acting insulin here within the name large indicates it is having a large duration

Of action so glycine is a long-acting insulin preparation similarly insulin d tumor can be remembered in this way here dt indicates the deletion of terminal so one of the terminal amino acid is going to be deleted in the dtml and another term mirror indicates meristic acid where the menistic acid is going to be added to the terminal so the terminal amino acid

Is removed and myristic acid is going to be added in the insulin dt mirror so these are the two long acting insulin preparations the insulin lotion is having an onset of action around two hours and duration of action is variable from 18 to 24 hours whereas insulin determines having onset of action around 1.5 hours duration of action is around 24 hours both of

These insulin preparations are long acting and they produce a basal release of insulin and particularly insulin d tumor will give no peak in the insulin release so it will give a basal release of insulin so first one is the insulin glycine within the long acting insulin preparations so here the amino acid sequence is going to be modified at two portions first one at

The terminal b 30th position and second one at the a21 position so both the terminals of h and b chain are going to be modified so here at the terminal 30th portion of b chain amino acid is not replaced but it is going to be added so two arginine molecules are going to be added to the b 30th position so that the chain length is going to be increased now b chain is

Having the 32 amino acids that’s what it’s saying the large b chain now at the 21st position glycine is going to replace aspartame so these are the modifications within the glycine glycine at the 21st portion and arginine at the 30th position but here argenini is not replacing it is going to be added to the existing chain now the clad gene is having an isoelectric

Point variable from 5.4 to 6.7 because of these structural modifications now here the ph is maintained at the acetic side within the injection which is responsible for solubilization of the insulin block chain now insulin is solubilized so it is having the clear appearance now when this insulin login is given by subcutaneous root at the site of injection insulin

Glargin is precipitated because of neutral ph when the ph changes from acidic side to the neutral side the solubility is decreased and glycine is going to be precipitated now this insulin is not easily soluble and it is slowly released such that it can produce long duration of action in this way insulin glycogen is designed to adjust the isoelectric point to

The acidic side next one is the insulin dtml insulin demand is modified where one of the amino acid is going to be deleted so this is the terminal amino acid at the 30th position this is going to be deleted and a fatty acid chain is going to be added that is nothing but the meristic acid now the amino acid at the 30th portion is removed and fatty acid is going

To be added such that it produces a long-acting insulin preparation now when this insulin retainer is given by subcutaneous root at the site of injection because of fatty acid it can bind to the albumin so from the albumin it is slowly released and absorbed and even after absorption it binds to the albumin within the plasma from which the drug is slowly released

That’s why insulin d tumor is again a long-acting insulin preparation fourth type of category is ultra acting insulin preparations one of the preparation is insulin deglu deck so here within the structure again the thermal amino acid is going to be modified with the glutamic acid so glutamic acid can replace the 10 ml amino acid and now here glutamic acid acts

As a spacer to bind with a fatty acid chain but now this fatty acid is c16 fatty dye acid it’s having a dicarboxylic acid this dicarboxylic acid can bind to this glutamic acid to form a amide linkage and this preparation acts as ultra long acting insulin now when this deep glue deck is given by subcutaneous root at the site of injection it forms multi hexamers

Which are slowly released to produce long duration of action so these are the various types of insulin preparations rapid acting intermediate acting long acting and ultra long acting insulin preparations in our next video we will discuss the different types of insulin mixtures and how they are administered so that’s for today hope you have enjoyed this video if

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Transcribed from video
Insulin preparations and classification By egpat