Prednisone- Glucocorticosteroids
Brooks Waite
Chemistry 263

Prednisone is a glucocorticosteroid. Glucocorticosteroids also called corticosteroids or even steroids are within our bodies naturally. The body uses these types of steroids primarily in carbohydrate, protein and fat metabolism. The other function they provide is with immune system response functions, specifically, anti-inflammatory responses from injury and allergies. One of our body’s innate immune responses is to swell at a site of infection or trauma. When properly used, corticosteroids can inhibit inflammation that the body is trying to induce. Prednisone is a specific glucocorticosteroid derived from cortisone. Cortisone is the basis for many types of steroids, including prednisone, which we have been able to synthesize to take advantage of their individual reactions and responses.
Many synthesized steroids that we have developed are still a precursor to the actual effective molecule that the body will convert into another more useful form that the body can take advantage of effectively. Prednisone will be converted into prednisolone and cortisone is converted to cortisol. There is a method to the madness of this approach of providing the necessary steroids to the body in specific forms. Because their effectiveness can be maximized by allowing the body's enzymes to convert specific molecules to the active molecules necessary for specific and most efficient uses, along with trying to minimize side products and side effects.

In 1950 Arthur Nobile developed a method to create prednisone and prednisolone through the oxidation of cortisone with the use of bacteria. Nobile opened the door to a multi-billion dollar industry of chemical synthesis of drugs with the use of microbes.
Originally, there were very few treatments for illnesses like rheumatoid arthritis, asthma, skin disorders, ulcerative colitis and cerebral edema caused by cancer. Cortisone was the primary treatment for most disorders that included any kind of inflammation.National Inventors Hall of Fame, 2007)
It wasn't until 1954 that a cost effective method for manufacturing was developed by Herschel Herzog of the Schering Corporation. The same methods of using a bacterium to oxidize cortisone to prednisone were utilized, just as did Arthur Nobile. Using this method Schering Corporation was able to synthesize other steroids as well such as hydrocortisone to prednisolone.

Medical uses of Prednisone and other corticosteroids and tissue specificity
Increased or extended inflammation within the body as a result of illness or trauma can cause detrimental effects beyond the actual illness or trauma. Inflammation is one of the body’s initial immune responses. As an example, if you were to bump into a sharp object and cut yourself, the skin around the site of the puncture can swell to isolate the injury. Swelling also triggers enzymes to initiate clotting, along with white blood cells to attack any foreign substance that may have entered the body. To a normal healthy body these responses do a great job of protection, but what happens if these responses happen within a body of the person that has an illness like asthma? Asthmatics lungs become less effective if the body’s immune response creates excessive swelling in the lungs and airway; so much so that it limits the ability of the alveoli absorb oxygen. In this case, corticosteroids inhaled directly into the lungs can limit the swelling and even reduce the swelling and allow the asthmatic to breathe freely again.
There is a long list of illnesses that glucocorticosteroids can help. I have already mentioned asthma, but also rheumatoid arthritis, Crohn's disease, hypercalcemia due to cancer, multiple sclerosis and in my case organ transplant. The list is too long to just lay out in a list because it continues to grow.
I briefly touched on the subject of tissue specificity and use of the corticosteroids. Within the advantages of these corticosteroids there are also a lot of side effects to consider. Side effects are one of the major considerations when choosing to use a corticosteroid or any type of steroid. Tissue specificity is a strong factor in deciding how to treat an illness. The example given above, the asthmatic would use an inhaler to deliver medication directly to the effected tissue like the lungs. The reason this is a much better delivery system is beyond just the obvious. It's true we would like to treat the swollen tissue quickly and directly with an inhaler, but it doesn't mean we can't use another means of delivery like oral medication. In some cases both will be prescribed, but if you are able to be specific, we can minimize the side effects. The oral medication must be broken down and metabolized and work its way throughout the body to the affected area to do its job. In some cases the medication must build up to a necessary level of saturation before it will start to work. In doing so, side effects may occur so aggressively that they could be worse than the illness itself. In these cases we keep in mind the specificity of steroids for specific tissue and illnesses. For example, a skin rash calls for a topical cream or when the asthmatic has an attack, an inhaler is used. For each treatment a specific corticosteroid may be prescribed. This specificity will be looked at in the next section.
Effective Conversion of synthesized prednisone to prednisolone and Cortisone to cortisol.
In the last section I introduced the idea of specificity of medication for the specific application. This idea is even more obvious when we look at the mechanisms and effects different medications have within the body.
The exact mechanisms of glucocorticosteroid synthesis are still not known. In Fact, for over 50 years scientists have been studying these mechanisms. However, there has been a great amount of studies on treatments using corticosteroids. This is where specific treatments with specific steroids have been confirmed. With the help of Jennie Mayer, I have found two articles that support each other. The first is from 1967 and gives great data on efficiency of the conversion of cortisone and prednisone to their active counter parts in the body (²Jenkins, 1967). The second article takes a 2009 view of the enzymes used to activate the steroids within the body including the specificity in use of the steroids as it relates to cardiovascular disease (³Hadoke, 2009). These articles support each other even though they are 40 years apart.
The way cortisone converts to cortisol and prednisone converts to prednisolone in the body is a perfect example of the efficiency of the body and the specificity that the body prefers.
In the article by Jenkins in 1967 it describes the use of synthesized cortisol from cortisone and then given to study subjects to compare the effective use of the synthesized cortisol compared to the cortisol that the body synthesizes from cortisone. The study also recognizes side products that can be created by the enzyme activity and conversion in the body. It was found that cortisone was more efficiently converted to cortisol for use by the body’s enzymes, in fact, 4 times more efficient. The lack of efficiency in the synthesized cortisol taken orally primarily in large doses was due to the reduction to tetra hydrocortisone. The side product is always a concern when chemical reactions are present.
The efficiency of prednisone and prednisolone and the body was also studied, but less drastic inefficiencies were found. Synthesized prednisolone was not so drastically reduced. The possible added cost to synthesize prednisolone or cortisol may be a consideration we have to look at if we are considering a commercial endeavor or added cost to a patient.
The article by Hadoke in 2009 focuses primarily on the enzyme function and the activation of the genes that turn on or off inflammation responses in the body. This concept ties in the idea of specificity of the type of glucocorticosteroid to use for specific tissues and treatments. Simply put, if you get an allergic skin rash a topical medication will work fine, but if you have chronic issues like transplantation of an organ that requires long-term treatment like immunosuppression where high levels of steroid saturation within the entire body would be necessary.

What is the difference of all these corticosteroids if they do a lot of the same things?
Well, they're not on the same, they all look alike but the small changes in their structure make all the difference in how we affect certain tissues in the body or how they are absorbed in the body, or how efficient they work in the body for specific treatments.
Let's look at the small changes of the cortisone molecule that converts to cortisol and prednisone and prednisolone.


Figure 1???

These simple alterations to the molecules are all it takes to change the function of each and there uses. All of the mechanisms are still not totally understood but are accomplished biologically with the help of bacterium to oxidize the cortisone molecule to the desired final product.

¹ National Inventors Hall of Fame, 2007. Hall of Fame/ Inventor Profile,

² Jenkins, J.S., Sampson, P.A., British Medical Journal, April 22, 1967, Pages 205-207. Conversion of cortisone to cortisol and prednisone to prednisolone.
³ Hadoke,P., Iqbal J., Walker,B., British Journal of Pharmacology (2009), 156, 689–712. Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease.
Tsang S., Garovoy, M., Benet, Z., International Journal of Immunopharmacology. Volume 7, Issue 5, 1985, Pages 731-737 Immunosuppressive activity of prednisone and prednisolone and their metabolic interconversion in the mixed lymphocyte reaction.
Hajós,G., Szporny,L.,Tuba, Z., Steroids, Volume 15, Issue 3, March 1970, Pages 449-458 11-Oxido-reduction of some natural and synthetic glucocorticoids in rat tissue in vitro.
Frerichs,V., Tornatore,K., Journal of Chromatography B, Volume 802, Issue 2, 5 April 2004, Pages 329-338.Determination of the glucocorticoids prednisone, prednisolone, dexamethasone, and cortisol in human serum using liquid chromatography coupled to tandem mass spectrometry.
J. Tamm, K. D. Voigt, U. Volkwein, P. Berle. Steroids, Volume 2, Issue 3, September 1963, Pages 279-295. Water soluble steroid conjugates II. Metabolism of prednisone-21-glycinate and of cortisol-21-sulfate in the perfused dog liver : comparison with prednisolone and cortisol .
U.S National Library of Medicine, April, 2011. Prednisone.

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