C11 Chemistry 151 Whitesell The Provisional Progress of Prednisone “This is my family, minus one. I know, I know… ‘Mitch is still with us.’ But he is not. Not the way he used to be and not the way I want him to be. And for those who grieve, absence is all that matters. Absence is why we grieve.” As Mitchell’s mother glanced over a family portrait, tears rolled down her cheek, her heart aching over the loss of her youngest son. In due time, she did not sulk anymore as slowly but surely, she turned her grief into determination. She made it a personal goal to share her story to the world: the tearful retellings reiterated her family’s hardships, strife and ultimate loss. Why? As an effort to educate the public about a horrid disease that took her son’s life in 2013: Duchenne Muscular Dystrophy. Diagnosed in 2005, the prognosis of Mitchell’s disease was to be wheelchair-bound for the next four to five years. However, Duchenne Muscular Dystrophy (abbreviated DMD) is known to be the irreversible deterioration of one’s muscles. The disease is progressive over time and ultimately terminal. Although Mitchell passed away last year at the age of ten, his family still continues to make a valiant effort in order to raise awareness for this rare disease, hoping other families will be blessed with a cure. There is no known cure for Duchenne Muscular Dystrophy, yet one drug has been proven to be very effective with minimal side effects. Prednisone is a corticosteroid better known as its brand names Deltasone® or PredniSONE Intensol®. It is the most commonly prescribed oral corticosteroid, known for its variety of medical uses against a wide range of diseases and health conditions which include asthma, rheumatic disorders, allergy reactions, Crohn’s disease, laryngitis, multiple sclerosis, lupus, and much more. Corticosteroids represent a class of chemicals including a steroid hormone that may be naturally produced in the body. They have similar chemical mechanisms in the human body and mimic the effects of hormones the human body produces naturally in the adrenal glands. When prescribed in doses that exceed one’s body's typical levels, Prednisone has the ability to suppress one’s own immune system, resulting in a patient being less prone to infections. This aids in the control of conditions in which an immune system mistakenly attacks its own tissues, thinking it to be a threat. This universal drug is particularly effective as an immunosuppressant and its effects vary based upon the dosage amount given to the patient (ranging from lower doses to treat mild allergic reactions to higher doses to treat certain types of cancer). Deltasone 20mg Tablet and PredniSONE Intensol Oral Solution Two-Dimensional and Three-Dimensional Structures of Prednisone In 1950, Arthur Nobile completed the very first isolation and structure identification of prednisone and prednisolone. However, it was not until five years later that the laboratories of Schering Corporation began to commercially produce Prednisone, by Nobile himself along with his team of chemists. After discovering the oxidative use of the bacterium Corynebacterium simplex, Nobile and his team were able to synthesis prednisone from cortisone, which is the exact same process used to synthesize prednisolone (active form of prednisone) from hydrocortisone. In 1955, Schering Corporation first introduced prednisone under its brand name DeltaCortef, serving as a replacement to cortisone. In 1948 when cortisone was first discovered to regenerate muscle movement in crippled patients, the “miracle drug” had harmful side effects when taken in large doses. Therefore, prednisone was utilized as a corticosteroid in high doses at a short period of time, in order to decrease the risks of dangerous side effects. The FDA first approved prednisone in 1955. It is prescribed to Duchenne Muscular Dystrophy patients in its pill or tablet form to be taken orally multiple times a day for a few weeks. This high dose is intended to reduce inflammation in the body. Prednisone has minimal side effects, dependent on how high or low the dosage prescribed to the patient. Common side effects are excess stomach acid secretion, trouble sleeping, increased hunger, and anxiety. Infrequent side effects of this drug include small red skin lesions, irregular periods, dry skin, puffy face (from water retention) and high blood sugar. Additional infrequent side effects may cause severe conditions such as osteoporosis, diabetes, and Cushing’s Syndrome. Although severe, these conditions are very rare and unlikely to occur. Relative to hydrocortisone, prednisone is about four times as potent as a glucocorticoid, which control cortisol levels in the body. Prednisone is an intermediate between hydrocortisone and dexamethasone in duration of action. Although the exact chemical mechanism of how prednisone works in one’s body, it is known that prednisone is rapidly absorbed across the gastrointestinal membrane following oral administration. Peak effects can be observed after one to two hours. The circulating drug binds extensively to the plasma proteins: albumin and transcortin, with only the unbound portion of a dose active. Systemic prednisone is quickly distributed into the kidneys, intestines, skin, liver and muscle. The drug is metabolized in the liver to its active form, prednisolone. Two-Dimensional and Three-Dimensional Structures of Prednisolone The active metabolite, prednisolone, is then further metabolized to inactive compounds. These inactive metabolites, as well as a small portion of unchanged drug, are excreted in the urine. The plasma elimination half-life is one hour whereas the biological half-life of prednisone is eighteen to thirty-six hours. Blood muscle enzymes tend to return to normal about four to six weeks after treatment starts. Patients aim to regain muscle strength in two to three months. Despite the fact that there is still no cure for Duchenne Muscular Dystrophy, Prednisone has a lot of potential to improve the lives of many. It is unfortunate for his family that Mitchell could not be saved. Yet may his young soul and his everlasting story still live on. If prednisone was discovered from basis of cortisone, there is high hope that another molecular discovery, branching from prednisone, may serve as a better medicine with lesser side effects. Prednisone is only the start of a new medicinal era where diseases such as Duchenne Muscular Dystrophy do not stand a chance. 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