While it is not necessary to understand the exact biochemical reactions of drugs people take, I still wonder whether sometimes it does make sense for patients to understand how a drug exactly works in a human body. Simply so people don't have the feeling that they are taking a "black box" pill that does something mysterious, which often creates fear in people's minds of what else it could do. I am not saying that understanding the biochemistry of how a drug interacts with a human body also explains potential side effects (it does not), but at least for me I like to know what the effects of a drug are that I actually take.
So, I start, here are the explanations of how I understand the drugs I take work on a biochemical level (It would be great if people could correct this understanding, if it is not a fair description of what is going on):
1. Azathioprine
Azathioprine is a prodrug of mercaptopurine (which we know as 6mp - the 6 comes from where the "mercapto"-subgroup is added to the purine molecule - the thing is actually called 6-[(1-Methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-7H-purine). A prodrug is a drug that is converted to another in the human body. Or in other words, aza and 6mp are effectively the same thing just that aza is converted later on into 6mp, which can have some benefits in terms of how people's bodies tolerate aza vs. 6mp.
Azathioprine, once converted into 6mp, is a structural analog to several of the various purines we have in our body. Purines are rather simple molecules, basically two 5-carbon atom rings put together. There are various purines in our body, they notably differ in what subgroups are bound to the core purine structure. For instance adenine (one of the 4 purines used in the base pair structure that make up DNA) has an amino-subgroup (NH2) and a hydrogen atom added at the second and sixth position.
Anyway, we need purines for DNA and RNA synthesis. No purines in the blood would mean cells could not duplicate. 6mp in our blood inhibites the DNA and RNA synthesis as it also has a molecule subgroup at its sixth position (a much larger molecule that is). In chemistry, this means 6mp and purines such as adenine are competing for the same function/"spots to dock" in the blood. Unlike other purines such as adenine or guanine, 6mp doesn't work for DNA/RNA synthesis. Once a certain 6mp concentration is added to the body, the synthesis process would thus need a much higher percentage of the actually working purines in the blood to keep the rate of DNA and RNA synthesis at the level as before 6mp is added. That reduces the growth rate of ALL cells. However, most notably it reduces the growth rate of certain cells with shorter lifetimes such as white blood cells (as cells with a shorter lifetimes have to be produced more often - at least this is how I understood it).
As white blood cells reduce in number, inflammation from an overreacting immune system gets less likely (the biochemistry of that effect is of course much more complex than the initial effect described above and isn't the focus of this thread). This also explains why azathioprine takes several weeks to be effective as the lifetime of a white blood cell is several weeks and only if you inhibit the creation of new white blood cells for about the same length as the average white blood cell life do you end up with a real immunosuppressive effect.
2. Iron supplement (I take iron (II) sulfate - FeSO4 orally)
As most people know, iron is relevant for hemoglobin synthesis and thus the capacity of transporting oxygen through blood (how the O2 to the heme group binding works chemically is more complicated, I understand it's a redox reaction plus several other factors... but that I think is not relevant here).
Iron is principally "stored" in larger molecules in the body - if iron were not bound by other larger molecules, it would have a toxic effect on the human body (by being a catalyst for the creation of free radical). Most notably, ferritin is the long time storage molecule for iron (another less known long term iron storage molecules is hemosiderin). Then there is transferrin which only binds very little of the totally available iron (0.1%) in the body, but is the protein that provides readily available iron for the synthesis of hemoglobin (basically an intermediary between the long-term storage and daily absorbed iron and hemoglobin). As a percentage 65% of the iron in the body is bound up in hemoglobin molecules in red blood cells, about 4% is bound up in myoglobin molecules (a hemoglobin variant in muscles) and around 30% of the iron in the body is stored as ferritin or hemosiderin in the spleen, the bone marrow and the liver.
Having described the above, the obvious reason why one would take FeSO4 in oral form is to increase the intake to increase the levels of both short term available iron and long-term storage iron. It is however interesting to know the biochemistry involved because of the following things:
A. when looking at your blood test, you will usually encounter several iron related tests: the ferritin level and the transferritin level (usually indicated by the total iron binding capacity (TIBC), an indirect measure of transferritin and/or by the measure called "serum iron" which isn't the actual iron in the serum, but is once again the transferritin level). Ferritin levels correlate quite well with anemia, that is in untreated anemia patients where the anemia is caused by iron deficiency, ferritin levels are low while transferritin/TIBC levels are actually usually elevated.
B. iron infusions/injections into the veins is actually not FeSO4 (toxic in blood) or ferritin, but a substitute bound Fe complex, such as iron sucrose, iron polymaltose or ferric carboxymaltose, none of which exist in blood naturally (at least not that I know). They are broken down in blood gradually. One reason why some people do not tolerate iron infusion well is exactly that the iron injected is not in the form the body stores it and needs to be converted first, which can have various side effects and strain the body's metabolism (leading to sickness, fever etc.).
Ok, that was a long post. I'd be interested in the biochemical explanations of other drugs people take or additions to the above.
So, I start, here are the explanations of how I understand the drugs I take work on a biochemical level (It would be great if people could correct this understanding, if it is not a fair description of what is going on):
1. Azathioprine
Azathioprine is a prodrug of mercaptopurine (which we know as 6mp - the 6 comes from where the "mercapto"-subgroup is added to the purine molecule - the thing is actually called 6-[(1-Methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-7H-purine). A prodrug is a drug that is converted to another in the human body. Or in other words, aza and 6mp are effectively the same thing just that aza is converted later on into 6mp, which can have some benefits in terms of how people's bodies tolerate aza vs. 6mp.
Azathioprine, once converted into 6mp, is a structural analog to several of the various purines we have in our body. Purines are rather simple molecules, basically two 5-carbon atom rings put together. There are various purines in our body, they notably differ in what subgroups are bound to the core purine structure. For instance adenine (one of the 4 purines used in the base pair structure that make up DNA) has an amino-subgroup (NH2) and a hydrogen atom added at the second and sixth position.
Anyway, we need purines for DNA and RNA synthesis. No purines in the blood would mean cells could not duplicate. 6mp in our blood inhibites the DNA and RNA synthesis as it also has a molecule subgroup at its sixth position (a much larger molecule that is). In chemistry, this means 6mp and purines such as adenine are competing for the same function/"spots to dock" in the blood. Unlike other purines such as adenine or guanine, 6mp doesn't work for DNA/RNA synthesis. Once a certain 6mp concentration is added to the body, the synthesis process would thus need a much higher percentage of the actually working purines in the blood to keep the rate of DNA and RNA synthesis at the level as before 6mp is added. That reduces the growth rate of ALL cells. However, most notably it reduces the growth rate of certain cells with shorter lifetimes such as white blood cells (as cells with a shorter lifetimes have to be produced more often - at least this is how I understood it).
As white blood cells reduce in number, inflammation from an overreacting immune system gets less likely (the biochemistry of that effect is of course much more complex than the initial effect described above and isn't the focus of this thread). This also explains why azathioprine takes several weeks to be effective as the lifetime of a white blood cell is several weeks and only if you inhibit the creation of new white blood cells for about the same length as the average white blood cell life do you end up with a real immunosuppressive effect.
2. Iron supplement (I take iron (II) sulfate - FeSO4 orally)
As most people know, iron is relevant for hemoglobin synthesis and thus the capacity of transporting oxygen through blood (how the O2 to the heme group binding works chemically is more complicated, I understand it's a redox reaction plus several other factors... but that I think is not relevant here).
Iron is principally "stored" in larger molecules in the body - if iron were not bound by other larger molecules, it would have a toxic effect on the human body (by being a catalyst for the creation of free radical). Most notably, ferritin is the long time storage molecule for iron (another less known long term iron storage molecules is hemosiderin). Then there is transferrin which only binds very little of the totally available iron (0.1%) in the body, but is the protein that provides readily available iron for the synthesis of hemoglobin (basically an intermediary between the long-term storage and daily absorbed iron and hemoglobin). As a percentage 65% of the iron in the body is bound up in hemoglobin molecules in red blood cells, about 4% is bound up in myoglobin molecules (a hemoglobin variant in muscles) and around 30% of the iron in the body is stored as ferritin or hemosiderin in the spleen, the bone marrow and the liver.
Having described the above, the obvious reason why one would take FeSO4 in oral form is to increase the intake to increase the levels of both short term available iron and long-term storage iron. It is however interesting to know the biochemistry involved because of the following things:
A. when looking at your blood test, you will usually encounter several iron related tests: the ferritin level and the transferritin level (usually indicated by the total iron binding capacity (TIBC), an indirect measure of transferritin and/or by the measure called "serum iron" which isn't the actual iron in the serum, but is once again the transferritin level). Ferritin levels correlate quite well with anemia, that is in untreated anemia patients where the anemia is caused by iron deficiency, ferritin levels are low while transferritin/TIBC levels are actually usually elevated.
B. iron infusions/injections into the veins is actually not FeSO4 (toxic in blood) or ferritin, but a substitute bound Fe complex, such as iron sucrose, iron polymaltose or ferric carboxymaltose, none of which exist in blood naturally (at least not that I know). They are broken down in blood gradually. One reason why some people do not tolerate iron infusion well is exactly that the iron injected is not in the form the body stores it and needs to be converted first, which can have various side effects and strain the body's metabolism (leading to sickness, fever etc.).
Ok, that was a long post. I'd be interested in the biochemical explanations of other drugs people take or additions to the above.
Last edited:
