57-556: Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma , COPD , and rheumatologic diseases . It is also used to treat high blood calcium due to cancer and adrenal insufficiency along with other steroids . It is taken by mouth . Common side effects may include cataracts , bone loss , easy bruising , muscle weakness, and thrush . Other side effects include weight gain, swelling, high blood sugar , increased risk of infection, and psychosis . It
114-599: A synthetic pregnane corticosteroid and derivative of cortisone and is also known as δ-cortisone or 1,2-dehydrocortisone or as 17α,21-dihydroxypregna-1,4-diene-3,11,20-trione. 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
171-477: A class of corticosteroids , which are a class of steroid hormones . Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell. The name "glucocorticoid" is a portmanteau ( gluco se + cort ex + ster oid ) and is composed from its role in regulation of glucose metabolism , synthesis in the adrenal cortex , and its steroidal structure (see structure below). Glucocorticoids are part of
228-427: A dose that provides approximately the same glucocorticoid effects as normal cortisol production; this is referred to as physiologic, replacement, or maintenance dosing. This is approximately 6–12 mg/m /day of hydrocortisone (m refers to body surface area (BSA), and is a measure of body size; an average man's BSA is 1.9 m ). Glucocorticoids cause immunosuppression , and the therapeutic component of this effect
285-445: A few days begins to produce suppression of the patient's adrenal glands suppressing hypothalamic corticotropin-releasing hormone (CRH) leading to suppressed production of adrenocorticotropic hormone (ACTH) by the anterior pituitary. With prolonged suppression, the adrenal glands atrophy (physically shrink), and can take months to recover full function after discontinuation of the exogenous glucocorticoid. During this recovery time,
342-643: A glucocorticoid, 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, thereby inducing a potent diuresis. At high doses it may be used to prevent rejection following organ transplant. 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
399-436: A lesser extent, after treatment, a condition known as " steroid dementia ". Glucocorticoids could act centrally, as well as peripherally, to assist in the normalization of extracellular fluid volume by regulating body's action to atrial natriuretic peptide (ANP). Centrally, glucocorticoids could inhibit dehydration-induced water intake; peripherally, glucocorticoids could induce a potent diuresis. Glucocorticoids bind to
456-600: A multitude of less-dramatic physiologic roles for glucocorticoids. Glucocorticoids have multiple effects on fetal development. An important example is their role in promoting maturation of the lung and production of the surfactant necessary for extrauterine lung function. Mice with homozygous disruptions in the corticotropin -releasing hormone gene (see below) die at birth due to pulmonary immaturity. In addition, glucocorticoids are necessary for normal brain development, by initiating terminal maturation, remodeling axons and dendrites, and affecting cell survival and may also play
513-491: A role in hippocampal development . Glucocorticoids stimulate the maturation of the Na /K /ATPase, nutrient transporters, and digestion enzymes, promoting the development of a functioning gastro-intestinal system. Glucocorticoids also support the development of the neonate's renal system by increasing glomerular filtration. Glucocorticoids act on the hippocampus , amygdala , and frontal lobes . Along with adrenaline , these enhance
570-892: A significant impact on vigilance ( attention deficit disorder ) and cognition (memory). This appears to follow the Yerkes-Dodson curve , as studies have shown circulating levels of glucocorticoids vs. memory performance follow an upside-down U pattern, much like the Yerkes-Dodson curve. For example, long-term potentiation (LTP; the process of forming long-term memories) is optimal when glucocorticoid levels are mildly elevated, whereas significant decreases of LTP are observed after adrenalectomy (low-glucocorticoid state) or after exogenous glucocorticoid administration (high-glucocorticoid state). Elevated levels of glucocorticoids enhance memory for emotionally arousing events, but lead more often than not to poor memory for material unrelated to
627-424: A wide range of effects, including, for example: The opposite mechanism is called transcriptional repression, or transrepression . The classical understanding of this mechanism is that activated glucocorticoid receptor binds to DNA in the same site where another transcription factor would bind, which prevents the transcription of genes that are transcribed via the activity of that factor. While this does occur,
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#1732775423041684-458: Is absorbed in the gastrointestinal tract and has a half-life of 2–3 hours. it has a volume of distribution of 0.4–1 L/kg. The drug is cleared by hepatic metabolism using cytochrome P450 enzymes. Metabolites are excreted in the bile and urine. "Lodotra" is the brand name of an oral formulation, which releases prednisone four hours after ingestion. It is indicated for rheumatoid arthritis with morning stiffness. Taken at 10 p.m., it releases
741-403: Is complicated. Dexamethasone decreases IFN-gamma stimulated Fc gamma RI expression in neutrophils while conversely causing an increase in monocytes . Glucocorticoids may also decrease the expression of Fc receptors in macrophages, but the evidence supporting this regulation in earlier studies has been questioned. The effect of Fc receptor expression in macrophages is important since it
798-405: Is generally considered safe in pregnancy and low doses appear to be safe while the user is breastfeeding . After prolonged use, prednisone must be stopped gradually. Prednisone is a prodrug and must be converted to prednisolone by the liver before it becomes active. Prednisolone then binds to glucocorticoid receptors , activating them and triggering changes in gene expression . Prednisone
855-412: Is mainly the decreases in the function and numbers of lymphocytes , including both B cells and T cells . The major mechanism for this immunosuppression is through inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells ( NF-κB ). NF-κB is a critical transcription factor involved in the synthesis of many mediators (i.e., cytokines) and proteins (i.e., adhesion proteins) that promote
912-673: Is more prominent in immature T cells still inside in the thymus, but peripheral T cells are also affected. The exact mechanism regulating this glucocorticoid sensitivity lies in the Bcl-2 gene. Glucocorticoids also suppress the humoral immunity , thereby causing a humoral immune deficiency . Glucocorticoids cause B cells to express smaller amounts of IL-2 and of IL-2 receptors . This diminishes both B cell clone expansion and antibody synthesis. The diminished amounts of IL-2 also cause fewer T lymphocyte cells to be activated. The effect of glucocorticoids on Fc receptor expression in immune cells
969-662: Is necessary for the phagocytosis of opsonised cells. This is because Fc receptors bind antibodies attached to cells targeted for destruction by macrophages. Glucocorticoids are potent anti-inflammatories, regardless of the inflammation's cause; their primary anti-inflammatory mechanism is lipocortin-1 (annexin-1) synthesis. Lipocortin-1 both suppresses phospholipase A2 , thereby blocking eicosanoid production, and inhibits various leukocyte inflammatory events ( epithelial adhesion , emigration , chemotaxis , phagocytosis , respiratory burst , etc.). In other words, glucocorticoids not only suppress immune response, but also inhibit
1026-669: Is released when a glucocorticoid binds to glucocorticoid receptor, and phosphorylates a protein that in turn displaces an adaptor protein from a receptor important in inflammation, epidermal growth factor , reducing its activity, which in turn results in reduced creation of arachidonic acid – a key proinflammatory molecule. This is one mechanism by which glucocorticoids have an anti-inflammatory effect. A variety of synthetic glucocorticoids, some far more potent than cortisol, have been created for therapeutic use. They differ in both pharmacokinetics (absorption factor, half-life, volume of distribution, clearance) and pharmacodynamics (for example
1083-740: Is the name used for pharmaceutical preparations of cortisol. The data below refer to oral administration. Oral potency may be less than parenteral potency because significant amounts (up to 50% in some cases) may not reach the circulation. Fludrocortisone acetate and deoxycorticosterone acetate are, by definition, mineralocorticoids rather than glucocorticoids, but they do have minor glucocorticoid potency and are included in this table to provide perspective on mineralocorticoid potency. Glucocorticoids may be used in low doses in adrenal insufficiency . In much higher doses, oral or inhaled glucocorticoids are used to suppress various allergic , inflammatory , and autoimmune disorders. Inhaled glucocorticoids are
1140-436: Is unlikely to relapse and have: Systemic corticosteroids may be stopped abruptly in those whose disease is unlikely to relapse and who have received treatment for three 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
1197-438: Is used as an antitumor drug . Prednisone is often also prescribed as a form of treatment for sudden sensorineural hearing loss (SSNHL). 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 doses of loop diuretics. In terms of the mechanism of action for this purpose: prednisone,
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#17327754230411254-477: Is why it is 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 , truncal weight gain, glaucoma and cataracts , diabetes mellitus type 2 , and depression upon dose reduction or cessation. Long-term steroids can also increase
1311-558: The adrenal cortex ), but is often used as a synonym for "glucocorticoid". Glucocorticoids are chiefly produced in the zona fasciculata of the adrenal cortex , whereas mineralocorticoids are synthesized in the zona glomerulosa . Cortisol (or hydrocortisone) is the most important human glucocorticoid. It is essential for life , and it regulates or supports a variety of important cardiovascular , metabolic , immunologic , and homeostatic functions. Increases in glucocorticoid concentrations are an integral part of stress response and are
1368-435: The feedback mechanism in the immune system , which reduces certain aspects of immune function, such as inflammation . They are therefore used in medicine to treat diseases caused by an overactive immune system , such as allergies , asthma , autoimmune diseases , and sepsis . Glucocorticoids have many diverse effects such as pleiotropy , including potentially harmful side effects . They also interfere with some of
1425-492: 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
1482-416: The abnormal mechanisms in cancer cells , so they are used in high doses to treat cancer. This includes inhibitory effects on lymphocyte proliferation, as in the treatment of lymphomas and leukemias , and the mitigation of side effects of anticancer drugs . Glucocorticoids affect cells by binding to the glucocorticoid receptor . The activated glucocorticoid receptor-glucocorticoid complex up-regulates
1539-638: The action of the kidneys . It is promoted by ventricular and atrial natriuretic peptides as well as calcitonin , and inhibited by chemicals such as aldosterone . Natriuresis lowers the concentration of sodium in the blood and also tends to lower blood volume because osmotic forces drag water out of the body's blood circulation and into the urine along with the sodium. Many diuretic drugs take advantage of this mechanism to treat medical conditions like hypernatremia and hypertension , which involve excess blood volume. Excess natriuresis can be caused by: Endogenous natriuretic hormones include: This
1596-478: The adrenal gland enough time to regain its function and endogenous production of steroids. 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
1653-503: The adrenal glands to begin functioning normally again. Prednisone may start to result in the suppression of the hypothalamic–pituitary–adrenal (HPA) axis if used at doses 7–10 mg or higher for several weeks. This is approximately equal to the amount of endogenous cortisol produced by the body every day. As such, the HPA axis starts to become suppressed and atrophy . If this occurs the patient should be tapered off prednisone slowly to give
1710-502: The advantage of only affecting the targeted area, thereby reducing side effects or potential interactions. In this case, the main compounds used are beclometasone , budesonide , fluticasone , mometasone and ciclesonide . In rhinitis, sprays are used. For asthma, glucocorticoids are administered as inhalants with a metered-dose or dry powder inhaler . In rare cases, symptoms of radiation induced thyroiditis has been treated with oral glucocorticoids. Glucocorticoids can be used in
1767-470: 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. Glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids ) are
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1824-670: The body's immune system. Glucocorticoid effects may be broadly classified into two major categories: immunological and metabolic . In addition, glucocorticoids play important roles in fetal development and body fluid homeostasis. Glucocorticoids function via interaction with the glucocorticoid receptor: Glucocorticoids are also shown to play a role in the development and homeostasis of T lymphocytes . This has been shown in transgenic mice with either increased or decreased sensitivity of T cell lineage to glucocorticoids. The name "glucocorticoid" derives from early observations that these hormones were involved in glucose metabolism . In
1881-447: The capacity of mineralocorticoid activity: retention of sodium (Na ) and water ; renal physiology ). Because they permeate the intestines easily, they are administered primarily per os ( by mouth ), but also by other methods, such as topically on skin . More than 90% of them bind different plasma proteins , though with a different binding specificity. Endogenous glucocorticoids and some synthetic corticoids have high affinity to
1938-531: The cytosolic glucocorticoid receptor , a type of nuclear receptor that is activated by ligand binding. After a hormone binds to the corresponding receptor, the newly formed complex translocates itself into the cell nucleus , where it binds to glucocorticoid response elements in the promoter region of the target genes resulting in the regulation of gene expression . This process is commonly referred to as transcriptional activation, or transactivation . The proteins encoded by these up-regulated genes have
1995-414: The disease may be needed during withdrawal to ensure that relapse does not occur. Prednisone is a synthetic glucocorticoid used for its anti-inflammatory and immunosuppressive properties. Prednisone is a prodrug; it is metabolised in the liver by 11-β-HSD to prednisolone, the active drug. Prednisone has no substantial biological effects until converted via hepatic metabolism to prednisolone . Prednisone
2052-416: 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 Addisonian 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
2109-597: The drug at around 2 a.m. The plasmic peak level is reached at 4 a.m., which is considered to be the optimal time for relieving morning stiffness. The drug was approved in the European Union , in January 2009. The pharmaceutical industry uses prednisone tablets for the calibration of dissolution testing equipment according to the United States Pharmacopeia (USP). Prednisone is
2166-543: The effects of shingles , lupus , myasthenia gravis , poison oak exposure, Ménière's disease , autoimmune hepatitis , giant cell arteritis , 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 organ transplant . Prednisone has also been used in the treatment of migraine headaches and cluster headaches and for severe aphthous ulcer . Prednisone
2223-646: The elaboration of selectively acting glucocorticoid drugs. Side effects include: In high doses, hydrocortisone (cortisol) and those glucocorticoids with appreciable mineralocorticoid potency can exert a mineralocorticoid effect as well, although in physiologic doses this is prevented by rapid degradation of cortisol by 11β-hydroxysteroid dehydrogenase isoenzyme 2 ( 11β-HSD2 ) in mineralocorticoid target tissues. Mineralocorticoid effects can include salt and water retention, extracellular fluid volume expansion, hypertension , potassium depletion, and metabolic alkalosis . Glucocorticoids cause immunosuppression , decreasing
2280-584: The expression of anti-inflammatory proteins in the nucleus (a process known as transactivation ) and represses the expression of pro-inflammatory proteins in the cytosol by preventing the translocation of other transcription factors from the cytosol into the nucleus ( transrepression ). Glucocorticoids are distinguished from mineralocorticoids and sex steroids by their specific receptors , target cells , and effects. In technical terms, " corticosteroid " refers to both glucocorticoids and mineralocorticoids (as both are mimics of hormones produced by
2337-535: The fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in the blood. Metabolic effects: Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism have effects on many systems. Some examples include inhibition of bone formation, suppression of calcium absorption (both of which can lead to osteoporosis ), delayed wound healing, muscle weakness, and increased risk of infection. These observations suggest
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2394-423: The formation of flashbulb memories of events associated with strong emotions, both positive and negative. This has been confirmed in studies, whereby blockade of either glucocorticoids or noradrenaline activity impaired the recall of emotionally relevant information. Additional sources have shown subjects whose fear learning was accompanied by high cortisol levels had better consolidation of this memory (this effect
2451-426: The function and/or numbers of neutrophils , lymphocytes (including both B cells and T cells ), monocytes , macrophages , and the anatomical barrier function of the skin. This suppression, if large enough, can cause manifestations of immunodeficiency , including T cell deficiency , humoral immune deficiency and neutropenia . In addition to the effects listed above, use of high-dose glucocorticoids for only
2508-704: The function of other transcription factors. This latter mechanism appears to be the most likely way that activated glucocorticoid receptor interferes with NF-κB - namely by recruiting histone deacetylase , which deacetylate the DNA in the promoter region leading to closing of the chromatin structure where NF-κB needs to bind. Activated glucocorticoid receptor has effects that have been experimentally shown to be independent of any effects on transcription and can only be due to direct binding of activated glucocorticoid receptor with other proteins or with mRNA. For example, Src kinase which binds to inactive glucocorticoid receptor,
2565-561: The immune response. Inhibition of this transcription factor, therefore, blunts the capacity of the immune system to mount a response. Glucocorticoids suppress cell-mediated immunity by inhibiting genes that code for the cytokines IL-1 , IL-2 , IL-3 , IL-4 , IL-5 , IL-6 , IL-8 and IFN-γ, the most important of which is IL-2. Smaller cytokine production reduces the T cell proliferation. Glucocorticoids, however, not only reduce T cell proliferation, but also lead to another well known effect - glucocorticoid-induced apoptosis. The effect
2622-538: The management of familial hyperaldosteronism type 1 . They are not effective, however, for use in the type 2 condition. Glucocorticoids could be used in the treatment of decompensated heart failure to potentiate renal responsiveness to diuretics, especially in heart failure patients with refractory diuretic resistance with large doses of loop diuretics. Resistance to the therapeutic uses of glucocorticoids can present difficulty; for instance, 25% of cases of severe asthma may be unresponsive to steroids. This may be
2679-421: The most commonly used biomarkers to measure stress. Glucocorticoids have numerous non-stress-related functions as well, and glucocorticoid concentrations can increase in response to pleasure or excitement. Various synthetic glucocorticoids are available; these are widely utilized in general medical practice and numerous specialties , either as replacement therapy in glucocorticoid deficiency or to suppress
2736-411: The patient is vulnerable to adrenal insufficiency during times of stress, such as illness. While suppressive dose and time for adrenal recovery vary widely, clinical guidelines have been devised to estimate potential adrenal suppression and recovery, to reduce risk to the patient. The following is one example: Natriuresis Natriuresis is the process of sodium excretion in the urine through
2793-417: The protein transcortin (also called corticosteroid-binding globulin), whereas all of them bind albumin . In the liver, they quickly metabolize by conjugation with a sulfate or glucuronic acid , and are secreted in the urine . Glucocorticoid potency, duration of effect, and the overlapping mineralocorticoid potency vary. Cortisol is the standard of comparison for glucocorticoid potency. Hydrocortisone
2850-500: The result of genetic predisposition, ongoing exposure to the cause of the inflammation (such as allergens ), immunological phenomena that bypass glucocorticoids, pharmacokinetic disturbances (incomplete absorption or accelerated excretion or metabolism) and viral and/or bacterial respiratory infections. Glucocorticoid drugs currently being used act nonselectively, so in the long run they may impair many healthy anabolic processes. To prevent this, much research has been focused recently on
2907-404: The results are not consistent for all cell types and conditions; there is no generally accepted, general mechanism for transrepression. New mechanisms are being discovered where transcription is repressed, but the activated glucocorticoid receptor is not interacting with DNA, but rather with another transcription factor directly, thus interfering with it, or with other proteins that interfere with
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#17327754230412964-555: The risk of osteoporosis , but research has found that few of these people were taking medications to protect bones. Prednisone also results in leukocytosis . Source: Source: 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,
3021-711: The second-line treatment for asthma . They are also administered as post-transplantory immunosuppressants to prevent the acute transplant rejection and the graft-versus-host disease . Nevertheless, they do not prevent an infection and also inhibit later reparative processes . Newly emerging evidence showed that glucocorticoids could be used in the treatment of heart failure to increase the renal responsiveness to diuretics and natriuretic peptides. Glucocorticoids are historically used for pain relief in inflammatory conditions. However, corticosteroids show limited efficacy in pain relief and potential adverse events for their use in tendinopathies . Any glucocorticoid can be given in
3078-408: The source of stress/emotional arousal. In contrast to the dose-dependent enhancing effects of glucocorticoids on memory consolidation, these stress hormones have been shown to inhibit the retrieval of already stored information. Long-term exposure to glucocorticoid medications, such as asthma and anti-inflammatory medication, has been shown to create deficits in memory and attention both during and, to
3135-570: The two main products of inflammation, prostaglandins and leukotrienes . They inhibit prostaglandin synthesis at the level of phospholipase A2 as well as at the level of cyclooxygenase /PGE isomerase (COX-1 and COX-2), the latter effect being much like that of NSAIDs , thus potentiating the anti-inflammatory effect. In addition, glucocorticoids also suppress cyclooxygenase expression. Glucocorticoids marketed as anti-inflammatories are often topical formulations, such as nasal sprays for rhinitis or inhalers for asthma . These preparations have
3192-486: Was more important in men). The effect that glucocorticoids have on memory may be due to damage specifically to the CA1 area of the hippocampal formation. In multiple animal studies, prolonged stress (causing prolonged increases in glucocorticoid levels) have shown destruction of the neurons in the hippocampus area of the brain, which has been connected to lower memory performance. Glucocorticoids have also been shown to have
3249-967: Was patented in 1954 and approved for medical use in the United States in 1955. It is on the World Health Organization's List of Essential Medicines . It is available as a generic medication . In 2022, it was the 30th most commonly prescribed medication in the United States, with more than 18 million prescriptions. Prednisone is used for many different autoimmune diseases and inflammatory conditions, including asthma , gout , COPD , CIDP , rheumatic disorders , allergic disorders, ulcerative colitis and Crohn's disease , granulomatosis with polyangiitis , adrenocortical insufficiency , hypercalcemia due to cancer, thyroiditis , laryngitis , severe tuberculosis , hives , eczema , lipid pneumonitis , pericarditis , multiple sclerosis , nephrotic syndrome , sarcoidosis , to relieve
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