Prednisone

Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant. It's used to treat certain inflammatory diseases (such as moderate allergic reactions), some autoimmune diseases, and (at higher doses) some types of cancer, but it has significant side effects.
==Medical uses==
Prednisone is used for many different autoimmune diseases and inflammatory conditions, including: asthma, COPD, CIDP, rheumatic disorders, allergic disorders, ulcerative colitism Crohn's disease, adrenocortical insufficiency, hypercalcemia due to cancer, thyroiditis, laryngitis, severe tuberculosis, hives, lipid pneumonitis, pericarditis, multiple sclerosis, nephrotic syndrome, sarcoidosis, to relieve the effects of shingles, lupus, myasthenia gravis, poison oak exposure, Ménière's disease, autoimmune hepatitis, the Herxheimer reaction that is common during the treatment of syphilis, Duchenne muscular dystrophy, uveitis, and as part of a drug regimen to prevent rejection after transplant.
Prednisone has also been used in the treatment of migraine headaches and cluster headaches and for severe aphthous ulcers. Prednisone is used as an anti-tumor drug. It's important in the treatment of acute lymphoblastic leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, and other hormone-sensitive tumors, in combination with other anticancer drugs.
Prednisone can be used in the treatment of decompensated heart failure to increase renal responsiveness to diuretics, especially in heart failure patients with refractory diuretic resistance with large dose of loop diuretics. In terms of the mechanism of action for this purpose: prednisone can improve renal responsiveness to atrial natriuretic peptide by increasing the density of natriuretic peptide receptor type A in the renal inner medullary collecting duct, inducing a potent diuresis.
Patients on prednisone therapy require frequent medical attention, generally to perform blood tests and to check blood pressure. Prednisone is only available with a prescription. Patients usually recognize improvement on prednisone without tests, such as reduction in swelling or pain. However, their condition should still be monitored even if improvement seems obvious.
==Contraindications and other relevant considerations==
*Patients with an infection, particularly a fungal infection (including skin fungus)
*Live virus vaccinations (before or after starting the drug)
*Any illness causing diarrhea
*Liver or kidney illness
*Heart disease
*High blood pressure
*Hypocalcemia
*Thyroid disorders
*Diabetes
*Malaria
*Tuberculosis
*Osteoporosis
*Glaucoma, cataracts, or herpes infection in the eyes
*Ulcer
*Clinical depression or other mental illness
*Pregnancy
*Alcohol
In addition, patients should wear a medic alert bracelet and inform any new treating physician they are on prednisone.
Prednisone overdoses are usually not dangerous, but the patient should seek immediate medical attention if, for example, they take more than the recommended dose in error. However, immediate medical attention should also be obtained if any of the following symptoms appear:
*Blurred vision, eye pain, or seeing halos around lights
*Swelling, rapid weight gain, shortness of breath
*Severe depression or sudden extreme mood changes, any change in personality or behavior
*Bloody or dark colored stool, or coughing up blood
*Pancreatitis
*Symptoms of hypocalcemia such as confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling
*Symptoms of very high blood pressure such as severe headache, blurred vision, tinnitus, anxiety, confusion, chest pain, shortness of breath, uneven heart rate or seizure.
Immediate medical attention is also required if a patient discontinues the drug and starts showing signs of withdrawal.
==Dosage==
Prednisone is usually taken orally, either in pill form or as a liquid. The medication should be stored at room temperature in a dry place. Dosage depends on the individual needs of the patient, but is taken on a regular basis according to the physician's instructions. A typical starting dose is 2 mg per kg of body weight with a maximum of 80mg per day, usually in 3-4 portions per day. After four weeks, the dose is usually reduced 25-50%. The dose is reduced further and only given every other day to prevent relapse when weaning a patient off the drug.
Pills come in several sizes: 1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg, and 50 mg. Time-released pills are only available in smaller doses: 1 mg, 2 mg, and 5 mg. Prednisone syrups are consistently prepared so that 1 ml of syrup contains 1mg of the drug. Concentrated liquid preparations can be taken with other liquids or soft food such as apple sauce. If a dose is missed, it should be taken as soon as the patient remembers unless it's almost time for the next dose. There are also preparations that can be delivered nasally, into the colon and intravenously.
Dosage may change due to other factors affecting the patient's health, such as developing an infection. Due to the possibility of stomach upset, it should be taken with food. If only a single daily dose is required, it should preferably be taken in the morning. Pills should be swallowed whole. Because of of dependency issues, prednisone should never be discontinued except under a doctor's orders.
Persons over the age of 65 are usually given smaller doses than other adults as their livers tend to process the drug more slowly. A normal adult dose will most likely result in higher than intended levels of the drug in the bloodstream.
When travelling with prednisone, it can be kept in carry-on luggage and X-rays will not affect it.
==Side effects==
Both the therapeutic and side effects of prednisone are due to the fact it mimics the effect of cortisol, a naturally occurring hormone produced by the adrenal glands. However, prednisone is several times more potent than cortisol for the same dose. First, both encourage the creation of glucose, which raises blood sugar. It they also activate chemical pathways that reduce stress and inflammation by suppressing the chemicals that cause these reactions. In addition, it weakens the response of both B cells and T cells. They both reduce bone formation. They both cause potassium to be released from cells in favor of sodium. It reduces the production of collagen, which also inhibits the formation of protein. They act as a diuretic (most likely to remove the drug through the kidneys). In the stomach, they increase the production of stomach acid. Although both stimulate the formation of memories, both damage cells in the hippocampus, making learning more difficult. Since in a person with normal cortisol production there's a daily cycle of cortisol production, interrupting that cycle often leads to issues with sleep and the production of ACTH, which affects mood.
Short-term side effects, as with all glucocorticoids, include high blood glucose levels (especially in patients with diabetes mellitus or on other medications that increase blood glucose, such as tacrolimus) and mineralocorticoid effects such as fluid retention. The mineralocorticoid effects of prednisone are minor, which is why it's not used in the management of adrenal insufficiency, unless a more potent mineralocorticoid is administered concomitantly.
It can also cause depression or depressive symptoms and anxiety in some individuals.
Long-term side effects include Cushing's syndrome, steroid dementia syndrome, weight gain in the torso, osteoporosis, glaucoma, cataracts, diabetes mellitus, and depression upon dose reduction or cessation.
The drug acts identically in both men and women so no side effect is significantly more common in either sex.
Physicians must always balance the benefits of prednisone or any steroid against its therapeutic effects. Among the strategies used to manage a patient's health are to lower the dose or to give the doses less frequently, to change the method of administering the drug and to encourage lifestyle changes that will assist in offsetting the side effects. Calcium or potassium supplements may be recommended.
===Major===
*Increased blood sugar for diabetics
*Difficulty controlling emotion
*Difficulty in maintaining train of thought
*Weight gain
*Immunosuppression
*Severe facial swelling ("moon face")
*Depression, mania, psychosis, or other psychiatric symptoms
*Unusual fatigue or weakness
*Mental confusion / indecisiveness
*Memory and attention dysfunction (Steroid dementia syndrome)
*Blurred vision
*Abdominal pain
*Peptic ulcer
*Painful hips or shoulders
*Steroid-induced osteoporosis
*Stretch marks
*Osteonecrosis – same as avascular necrosis
*Insomnia
*Severe joint pain
*Cataracts or glaucoma
*Anxiety
*Black stool
*Bloating
*Severe swelling
*Mouth sores or dry mouth
*Avascular necrosis
*Hepatic steatosis
===Minor===
*Anxiety
*Acne
*Skin rash
*Appetite gain
*Hyperactivity
*Increased thirst
*Frequent urination
*Diarrhea
*Reduced intestinal flora
*Leg pain/cramps
*Sensitive teeth
*Headache
*Induced vomiting
===Dependency===
Adrenal suppression will begin to occur if prednisone is taken for longer than seven days. Eventually, this may cause the body to temporarily lose the ability to manufacture natural corticosteroids (especially cortisol), which results in dependence on prednisone. For this reason, prednisone should not be abruptly stopped if taken for more than seven days; instead, the dosage should be gradually reduced. This weaning process may be over a few days if the course of prednisone was short, but may take weeks or months if the patient had been on long-term treatment. Abrupt withdrawal may lead to an Addison crisis. For those on chronic therapy, alternate-day dosing may preserve adrenal function and thereby reduce side effects.
Glucocorticoids act to inhibit feedback of both the hypothalamus, decreasing corticotropin-releasing hormone (CRH), and corticotrophs in the anterior pituitary gland, decreasing the amount of adrenocorticotropic hormone (ACTH). For this reason, glucocorticoid analogue drugs such as prednisone down-regulate the natural synthesis of glucocorticoids. This mechanism leads to dependence in a short time and can be dangerous if medications are withdrawn too quickly. The body must have time to begin synthesis of CRH and ACTH and for the adrenal glands to begin functioning normally again.
Long-term use often leads to atrophy of the adrenal glands.
===Withdrawal===
The magnitude and speed of dose reduction in corticosteroid withdrawal should be determined on a case-by-case basis, taking into consideration the underlying condition being treated, and individual patient factors such as the likelihood of relapse and the duration of corticosteroid treatment. Gradual withdrawal of systemic corticosteroids should be considered in those whose disease is unlikely to relapse and have:
*Received more than 40 mg prednisone (or equivalent) daily for more than 1 week
*Been given repeat doses in the evening
*Received more than 3 weeks' treatment
*Recently received repeated courses (particularly if taken for longer than 3 weeks)
*Taken a short course within 1 year of stopping long-term therapy
*Other possible causes of adrenal suppression
Systemic corticosteroids may be stopped abruptly in those whose disease is unlikely to relapse and who have received treatment for 3 weeks or less and who are not included in the patient groups described above.
During corticosteroid withdrawal, the dose may be reduced rapidly down to physiological doses (equivalent to prednisolone 7.5 mg daily) and then reduced more slowly. Assessment of the disease may be needed during withdrawal to ensure that relapse does not occur.
==Drug and food interactions==
Prednisone has known medicine interactions with Amphotericin B, Cyclosporin, Digoxin, Digitalis, St. John's Wort, some antibiotics, some anti-fungal medications, the contraceptive pill and other hormone supplements, blood thinners, diuretics, Hepatitis C medications, HIV medications, insulin and other orally taken diabetes mellitus medications, some NSAIDs, anti-seizure medications, and tuberculosis medications. A patient may also have to avoid certain foods, such as grapefruit juice.
==Pharmacology==
Prednisone has no substantial biological effects until converted via hepatic metabolism to prednisolone. It mimics the action of cortisol. It has a half-life of 3-4 hours in adults, and 1-2 hours of children. It's removed by the kidneys and disposed of in the urine.
Prednisone pills have a long shelf life, but syrups should be disposed of if the bottle was opened over 90 days before.
==Industry==
The pharmaceutical industry uses prednisone tablets for the calibration of dissolution testing equipment according to the United States Pharmacopeia (USP).
==Chemistry==
Prednisone is a synthetic pregnane corticosteroid and derivative of cortisone and is also known as δ1-cortisone or 1,2-dehydrocortisone or as 17α,21-dihydroxypregna-1,4-diene-3,11,20-trione. Unlike many drugs, prednisone is a "small molecule". It's built around a matrix of carbon rings (the black hexagons in the diagram) with oxygen (red) and hydrogen (white) atoms. It has the chemical formula C21H26O5.
==History==
The first isolation and structure identifications of prednisone and prednisolone were done in 1950 by Arthur Nobile. The first commercially feasible synthesis of prednisone was carried out in 1955 in the laboratories of Schering Corporation, which later became Schering-Plough Corporation, by Arthur Nobile and coworkers. They discovered that cortisone could be microbiologically oxidized to prednisone by the bacterium Corynebacterium simplex. The same process was used to prepare prednisolone from hydrocortisone.
The enhanced adrenocorticoid activity of these compounds over cortisone and hydrocortisone was demonstrated in mice.
Prednisone and prednisolone were introduced in 1955 by Schering and Upjohn, under the brand names Meticorten and Delta-Cortef, respectively. It was approved by the FDA the same year. These prescription medicines are now available from a number of manufacturers as generic drugs. Generic preparations generally cost about $20 (U.S.) for a month's supply.
==On the Show==
Prednisone is one of the most often mentioned pharmaceuticals on the show. It's House's steroid drug of choice and he frequently uses it as part of a diagnostic trial.
*In the Pilot, he suspects Rebecca Adler has vasculitis and gives her prednisone without confirming. Cuddy is furious when she learns this, but backs off when Rebecca quickly improves. However, the steroids were really treating inflammation related to her neurocysticercosis.
*In Damned If You Do, House prescribes prednisone believing Sister Mary Augustine has Churg-Strauss syndrome. However, when she becomes immunocompromised, Cuddy blames it on the treatment and discontinues the drug.
*In Spin, believing Jeff Forrester has been abusing erythropoietin, he administers prednisone to correct pure red cell aplasia.
*When Kayla McGinley is diagnosed with Behcet's disease in The Mistake, Chase prescribes prednisone. However, he comes to the incorrect conclusion later on that her stomach pain is due to the drug rather than to a bleeding ulcer.
*The most interesting exchange about the use of prednisone is in Frozen. Believing that Dr. Cate Milton is suffering from an autoimmune disease, he suggests that she take prednisone to see if the symptoms improve. She refuses as, being at an Antarctic research station, she has a limited supply which she may need to treat someone with asthma. Instead, she improvises a LE Prep. When that is inconclusive, she collapses before they can see if the intense cold improves her symptoms.
*In Wilson's Heart, House suggests giving Amber Volakis steroids because she might have an autoimmune condition, but Wilson refuses.
*In Big Baby, House treats Sarah's condition with a combination of methotrexate and prednisone.
*In Small Sacrifices, when Ramon Silva doesn't respond to prednisone after his diagnosis of multiple sclerosis, they realize he has a rare and more deadly variant, Marberg's multiple sclerosis.
*In Family Practice, Dr. Marty Kaufman believes Arlene Cuddy has lupus and starts treating her with prednisone. However, House believes that Arlene has endocarditis and wants to treat her with antibiotics as steroids will kill someone with endocarditis. They obtain Lisa Cuddy's help in switching out the meds, but then Arlene develops symptoms of an allergy, leaving Kaufman thoroughly confused. He discontinues the prednisone and starts Arlene on antibiotics himself. Martha M. Masters finally figures out that House is treating Arlene behind Kaufman's back with Cuddy's assistance and, despite House's threat to have her thrown out of med school and sent to jail, she tells Kaufman the truth.
*House first treats Danny Jennings with prednisone at the beginning of Fall From Grace.
*In Twenty Vicodin, House believes Nick has lupus and tries to convince Jessica Adams to treat him with prednisone.
===Links===
*Prednisone at Wikipedia - This article uses content from the Wikipedia article under the Creative Commons license
*Prednisone at drugs.com
*Prednisone at MedicineNet.com
*Prednisone at the Mayo Clinic
*Prednisone at MedlinePlus
This article was the featured article for January, 2018.
Category:Pharmaceuticals
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