Corticosteroid

Corticosteroid
Drug class
Cortisol (hydrocortisone), a corticosteroid with both glucocorticoid and mineralocorticoid activity and effects.
Class identifiers
SynonymsCorticoid
UseVarious
ATC codeH02
Biological targetGlucocorticoid receptor, Mineralocorticoid receptor
Chemical classSteroids
Legal status
In Wikidata

Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, and also their synthetic analogues. The two main classes of corticosteroids – glucocorticoids and mineralocorticoids – are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

Some common naturally occurring steroid hormones are cortisol (C
21H
30O
5), corticosterone (C
21H
30O
4), cortisone (C
21H
28O
5) and aldosterone (C
21H
28O
5) (cortisone and aldosterone are isomers). The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone.

In medical usage, corticosteroid is often used as a synonym for glucocorticoids, the most widely used class of corticosteroid medication.

Etymology

The etymology of the cortico- part of the name refers to the adrenal cortex, which makes these steroid hormones. Thus a corticosteroid is a "cortex steroid".

Classes

Cortisol
Cortisone
Corticosterone
Aldosterone

Medical uses

Synthetic pharmaceutical drugs with corticosteroid-like effects are used in a variety of conditions, ranging from hematological neoplasms to brain tumors or skin diseases. Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone (Florinef) is a synthetic mineralocorticoid. Hydrocortisone (cortisol) is typically used for replacement therapy, e.g. for adrenal insufficiency and congenital adrenal hyperplasia.[citation needed]

Medical conditions treated with systemic corticosteroids (this list applies to glucocorticoids):

Topical formulations are also available for the skin, eyes (uveitis), lungs (asthma), nose (rhinitis), and bowels. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists (e.g., ondansetron).[citation needed]

Corticosteroids have been widely used in treating people with traumatic brain injury. A systematic review identified 20 randomised controlled trials and included 12,303 participants, then compared patients who received corticosteroids with patients who received no treatment. The authors recommended people with traumatic head injury should not be routinely treated with corticosteroids.

Pharmacology

Corticosteroids act as agonists of the glucocorticoid receptor and/or the mineralocorticoid receptor.

In addition to their corticosteroid activity, some corticosteroids may have some progestogenic activity and may produce sex-related side effects.

Adverse effects

Lower arm of a 47-year-old female showing skin damage caused by topical corticosteroid (glucocorticoid) use.

Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome. Typical mineralocorticoid side-effects are hypertension (abnormally high blood pressure), steroid induced diabetes mellitus, psychosis, poor sleep, hypokalemia (low potassium levels in the blood), hypernatremia (high sodium levels in the blood) without causing peripheral edema, metabolic alkalosis and connective tissue weakness. Wound healing or ulcer formation may be inhibited by the immunosuppressive effects.[citation needed]

A variety of steroid medications, from anti-allergy nasal sprays (Nasonex, Flonase) to topical skin creams, to eye drops (Tobradex), to prednisone have been implicated in the development of central serous retinopathy (CSR).

Use of corticosteroids has numerous side-effects, some of which may be severe:

Neuropsychiatric
steroid psychosis, and anxiety, depression. (This applies mainly to glucocorticoids as they mimic the effect of cortisol. The mineralocorticoid receptor also plays a role in fear extinction, but is not as pronounced in its effects.)
Therapeutic doses of glucocorticoids may cause a feeling of artificial well-being known as "steroid euphoria". Rare case reports of corticosteroid (mainly glucocorticoid) misuse, addiction, and dependence due to euphoria exist.
The neuropsychiatric effects are partly mediated by sensitization of the body to the actions of adrenaline. Therapeutically, the bulk of corticosteroid dose is given in the morning to mimic the body's diurnal rhythm; if given at night, the feeling of being energized will interfere with sleep. An extensive review is provided by Flores and Gumina.
Cardiovascular
Corticosteroids (mineralocorticoids) can cause sodium retention through a direct action on the kidney, in a manner analogous to aldosterone. This can result in fluid retention and hypertension.
Metabolic/Endocrine
Corticosteroids (glucocorticoids) cause a movement of body fat to the face and torso, resulting in "moon face", "buffalo hump", and "pot belly" or "beer belly", and cause movement of body fat away from the limbs. This has been termed corticosteroid-induced lipodystrophy. Due to the diversion of amino-acids to glucose, they are considered anti-anabolic, and long term therapy can cause muscle wasting (muscle atrophy). Besides muscle atrophy, steroid myopathy includes muscle pains (myalgias), muscle weakness (typically of the proximal muscles), serum creatine kinase normal, EMG myopathic, and some have type II (fast-twitch/glycolytic) fibre atrophy.
By increasing the production of glucose from amino-acid breakdown and opposing the action of insulin, corticosteroids (glucocorticoids) can cause hyperglycemia, insulin resistance and diabetes mellitus.
Skeletal
Steroid-induced osteoporosis may be a side-effect of long-term corticosteroid (glucocorticoid) use. Use of inhaled corticosteroids among children with asthma may result in decreased height.
Gastro-intestinal
While cases of colitis have been reported, corticosteroids (glucocorticoids) are often prescribed when the colitis, although due to suppression of the immune response to pathogens, should be considered only after ruling out infection or microbe/fungal overgrowth in the gastrointestinal tract. While the evidence for corticosteroids causing peptic ulceration is relatively poor except for high doses taken for over a month, the majority of doctors as of 2010 still believe this is the case, and would consider protective prophylactic measures.
Eyes
chronic use may predispose to cataract and glaucoma. Clinical and experimental evidence indicates that corticosteroids can cause permanent eye damage by inducing central serous retinopathy (CSR, also known as central serous chorioretinopathy, CSC). This should be borne in mind when treating patients with optic neuritis. There is experimental and clinical evidence that, at least in optic neuritis, speed of treatment initiation is important.
Vulnerability to infection
By suppressing immune reactions (which is one of the main reasons for their use in allergies), glucocorticoids may cause infections to flare up, notably candidiasis.
Severe amoebic colitis
Fulminant amoebic colitis is associated with high case fatality and can occur in patients infected with the parasite Entamoeba histolytica after exposure to glucocorticoid medications.
Pregnancy
Corticosteroids have a low but significant teratogenic effect, causing a few birth defects per 1,000 pregnant women treated. Corticosteroids are therefore contraindicated in pregnancy.
Habituation
Topical steroid addiction (TSA) or red burning skin has been reported in long-term users of topical steroids (glucocorticoids), users who applied topical steroids to their skin over a period of weeks, months, or years. TSA is characterised by uncontrollable, spreading dermatitis and worsening skin inflammation which requires a stronger topical steroid to get the same result as the first prescription. When topical steroid medication is lost, the skin experiences redness, burning, itching, hot skin, swelling, and/or oozing for a length of time. This is also called 'red skin syndrome' or 'topical steroid withdrawal' (TSW). After the withdrawal period is over the atopic dermatitis can cease or is less severe than it was before.
Children
In children the short term use of steroids (glucocorticoids) by mouth increases the risk of vomiting, behavioral changes, and sleeping problems.
Dysphonia
Inhaled corticosteroids (glucocorticoids) are used for treatment of asthma as a standard treatment. This can cause local adverse effects like vocal cord dysfunction.

Biosynthesis

Steroidogenesis, including corticosteroid biosynthesis.

The corticosteroids are synthesized from cholesterol within the adrenal cortex. Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase).[citation needed]

Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions), but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona fasciculata and zona glomerulosa.[citation needed]

Classification

By chemical structure

In general, corticosteroids are grouped into four classes, based on chemical structure. Allergic reactions to one member of a class typically indicate an intolerance of all members of the class. This is known as the "Coopman classification".

The highlighted steroids are often used in the screening of allergies to topical steroids.

Group A – Hydrocortisone type

Hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone, methylprednisolone, and prednisone.

Amcinonide, budesonide, desonide, fluocinolone acetonide, fluocinonide, halcinonide, triamcinolone acetonide, and Deflazacort (O-isopropylidene derivative)

Group C – Betamethasone type

Beclometasone, betamethasone, dexamethasone, fluocortolone, halometasone, and mometasone.

Group D – Esters

Group D1 – Halogenated (less labile)

Alclometasone dipropionate, betamethasone dipropionate, betamethasone valerate, clobetasol propionate, clobetasone butyrate, fluprednidene acetate, and mometasone furoate.

Group D2 – Labile prodrug esters

Ciclesonide, cortisone acetate, hydrocortisone aceponate, hydrocortisone acetate, hydrocortisone buteprate, hydrocortisone butyrate, hydrocortisone valerate, prednicarbate, and tixocortol pivalate.

By route of administration

Topical steroids

For use topically on the skin, eye, and mucous membranes.

Topical corticosteroids are divided in potency classes I to IV in most countries (A to D in Japan). Seven categories are used in the United States to determine the level of potency of any given topical corticosteroid.

Inhaled steroids

For nasal mucosa, sinuses, bronchi, and lungs.

This group includes:

There also exist certain combination preparations such as Advair Diskus in the United States, containing fluticasone propionate and salmeterol (a long-acting bronchodilator), and Symbicort, containing budesonide and formoterol fumarate dihydrate (another long-acting bronchodilator). They are both approved for use in children over 12 years old.

Oral forms

Such as prednisone, prednisolone, methylprednisolone, or dexamethasone.

Systemic forms

Available in injectables for intravenous and parenteral routes.

History

Introduction of early corticosteroids
CorticosteroidIntroduced
Cortisone1948
Hydrocortisone1951
Fludrocortisone acetate1954
Prednisolone1955
Prednisone1955
Methylprednisolone1956
Triamcinolone1956
Dexamethasone1958
Betamethasone1958
Triamcinolone acetonide1958
Fluorometholone1959
Deflazacort1969

Tadeusz Reichstein, Edward Calvin Kendall, and Philip Showalter Hench were awarded the Nobel Prize for Physiology and Medicine in 1950 for their work on hormones of the adrenal cortex, which culminated in the isolation of cortisone.

Initially hailed as a miracle cure and liberally prescribed during the 1950s, steroid treatment brought about adverse events of such a magnitude that the next major category of anti-inflammatory drugs, the nonsteroidal anti-inflammatory drugs (NSAIDs), was so named in order to demarcate from the opprobrium.

Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a 36-step process that started with deoxycholic acid, which was extracted from ox bile. The low efficiency of converting deoxycholic acid into cortisone led to a cost of US$200 per gram in 1947. Russell Marker, at Syntex, discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams. His conversion of diosgenin into progesterone by a four-step process now known as Marker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception.

In 1952, D.H. Peterson and H.C. Murray of Upjohn developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone. The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US$6 per gram[when?], falling to $0.46 per gram by 1980. Percy Julian's research also aided progress in the field. The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s.[citation needed]

Corticosteroids were voted Allergen of the Year in 2005 by the American Contact Dermatitis Society.

See also

References

  1. 1 2 3 Nussey S, Whitehead S (2001). "The adrenal gland". Endocrinology: An Integrated Approach. Oxford: BIOS Scientific Publishers.
  2. 1 2 3 4 5 6 7 Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, et al. (August 2013). "A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy". Allergy, Asthma, and Clinical Immunology. 9 (1) 30. doi:10.1186/1710-1492-9-30. PMC 3765115. PMID 23947590.
  3. ↑ Faggiano A, Mazzilli R, Natalicchio A, Adinolfi V, Argentiero A, Danesi R, et al. (December 2022). "Corticosteroids in oncology: Use, overuse, indications, contraindications. An Italian Association of Medical Oncology (AIOM)/ Italian Association of Medical Diabetologists (AMD)/ Italian Society of Endocrinology (SIE)/ Italian Society of Pharmacology (SIF) multidisciplinary consensus position paper". Critical Reviews in Oncology/Hematology. 180 103826. doi:10.1016/j.critrevonc.2022.103826. hdl:10447/582211. PMID 36191821. S2CID 252663155.
  4. ↑ Mohamadi A, Chan JJ, Claessen FM, Ring D, Chen NC (January 2017). "Corticosteroid Injections Give Small and Transient Pain Relief in Rotator Cuff Tendinosis: A Meta-analysis". Clinical Orthopaedics and Related Research. 475 (1): 232–243. doi:10.1007/s11999-016-5002-1. PMC 5174041. PMID 27469590.
  5. ↑ Alderson P, Roberts I. "Plain Language Summary". Corticosteroids for acute traumatic brain injury. The Cochrane Collaboration. p. 2.
  6. ↑ Alderson P, Roberts I (January 2005). Alderson P (ed.). "Corticosteroids for acute traumatic brain injury". The Cochrane Database of Systematic Reviews. 2005 (1) CD000196. doi:10.1002/14651858.CD000196.pub2. PMC 7043302. PMID 15674869.
  7. ↑ Diego Alvarez de la Rosa, Zuleima Ramos-Hernández, Julián Weller-Pérez, Thomas A. Johnson, Gordon L. Hager, The impact of mineralocorticoid and glucocorticoid receptor interaction on corticosteroid transcriptional outcomes, Molecular and Cellular Endocrinology, Volume 594, 2024, 112389, ISSN 0303-7207
  8. ↑ Lumry WR (October 1999). "A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis". The Journal of Allergy and Clinical Immunology. 104 (4 Pt 1): S150–S158. doi:10.1016/s0091-6749(99)70311-8. PMID 10518812.
  9. ↑ Brook EM, Hu CH, Kingston KA, Matzkin EG (March 2017). "Corticosteroid Injections: A Review of Sex-Related Side Effects". Orthopedics. 40 (2): e211–e215. doi:10.3928/01477447-20161116-07. PMID 27874912.
  10. ↑ Luzzani F, Gallico L, Glässer A (1982). "In vitro and ex vivo binding to uterine progestin receptors of the rat as a tool to assay progestational activity of glucocorticoids". Methods and Findings in Experimental and Clinical Pharmacology. 4 (4): 237–242. PMID 7121132.
  11. ↑ Cunningham GR, Goldzieher JW, de la Pena A, Oliver M (January 1978). "The mechanism of ovulation inhibition by triamcinolone acetonide". The Journal of Clinical Endocrinology and Metabolism. 46 (1): 8–14. doi:10.1210/jcem-46-1-8. PMID 376542.
  12. ↑ Werner R (2005). A massage therapist's guide to Pathology (3rd ed.). Pennsylvania: Lippincott Williams & Wilkins.
  13. ↑ Carvalho-Recchia CA, Yannuzzi LA, Negrão S, Spaide RF, Freund KB, Rodriguez-Coleman H, et al. (October 2002). "Corticosteroids and central serous chorioretinopathy". Ophthalmology. 109 (10): 1834–1837. doi:10.1016/S0161-6420(02)01117-X. PMID 12359603.
  14. ↑ "The New York Times :: A Breathing Technique Offers Help for People With Asthma". buteykola.com. Archived from the original on 2012-07-24. Retrieved 2012-11-30.
  15. ↑ Hall R. "Psychiatric Adverse Drug Reactions: Steroid Psychosis". Director of Research Monarch Health Corporation Marblehead, Massachusetts. Archived from the original on 2013-07-17. Retrieved 2013-06-23.
  16. ↑ Korte SM (March 2001). "Corticosteroids in relation to fear, anxiety and psychopathology". Neuroscience and Biobehavioral Reviews. 25 (2): 117–142. Bibcode:2001NBRev..25..117K. doi:10.1016/S0149-7634(01)00002-1. PMID 11323078. S2CID 8904351.
  17. ↑ Swinburn CR, Wakefield JM, Newman SP, Jones PW (December 1988). "Evidence of prednisolone induced mood change ('steroid euphoria') in patients with chronic obstructive airways disease". British Journal of Clinical Pharmacology. 26 (6): 709–713. doi:10.1111/j.1365-2125.1988.tb05309.x. PMC 1386585. PMID 3242575.
  18. ↑ Kenna HA, Poon AW, de los Angeles CP, Koran LM (October 2011). "Psychiatric complications of treatment with corticosteroids: review with case report". Psychiatry Clin Neurosci. 65 (6): 549–560. doi:10.1111/j.1440-1819.2011.02260.x. PMID 22003987. Rarely, corticosteroids have been abused for their euphoria-producing effects, producing drug dependency.31–33
  19. ↑ Warrington TP, Bostwick JM (October 2006). "Psychiatric adverse effects of corticosteroids". Mayo Clin Proc. 81 (10): 1361–1367. doi:10.4065/81.10.1361. PMID 17036562. CORTICOSTEROID ABUSE: Several case reports describe corticosteroid abuse or dependence driven by the euphoria these medications can induce. These cases typically involve high-dose oral or intravenous formulations, but at least 1 case of dexamethasone nasal spray abuse has been reported.33 Most cases of corticosteroid abuse have been described in patients with a premorbid history of either psychiatric illness or drug or alcohol dependence.34
  20. ↑ Jacobson L (April 2014). "Hypothalamic-pituitary-adrenocortical axis: neuropsychiatric aspects". Compr Physiol. 4 (2): 715–738. doi:10.1002/cphy.c130036. PMID 24715565. Glucocorticoids can also have mood-elevating effects, whose loss might fit better into a model of GR-impaired depression (392). Such effects are manifested in psychiatrically normal subjects as euphoria after exogenous administration, as depression after steroid withdrawal, and in a few cases, as steroid abuse (50, 210, 394). Mood improvements after glucocorticoid treatment occur before significant amelioration of the diseases for which the steroids were prescribed (373, 394), making it unlikely that euphoric effects were due to relief of disease symptoms. [...]
  21. ↑ Benjamin H. Flores and Heather Kenna Gumina (November 30, 2003). "The Neuropsychiatric Sequelae of Steroid Treatment".
  22. ↑ Hasselgren PO, Alamdari N, Aversa Z, Gonnella P, Smith IJ, Tizio S (July 2010). "Corticosteroids and muscle wasting: role of transcription factors, nuclear cofactors, and hyperacetylation". Current Opinion in Clinical Nutrition and Metabolic Care. 13 (4): 423–428. doi:10.1097/MCO.0b013e32833a5107. PMC 2911625. PMID 20473154.
  23. ↑ Rodolico C, Bonanno C, Pugliese A, Nicocia G, Benvenga S, Toscano A (September 2020). "Endocrine myopathies: clinical and histopathological features of the major forms". Acta Myologica. 39 (3): 130–135. doi:10.36185/2532-1900-017. PMC 7711326. PMID 33305169.
  24. ↑ Donihi AC, Raval D, Saul M, Korytkowski MT, DeVita MA (2006). "Prevalence and predictors of corticosteroid-related hyperglycemia in hospitalized patients". Endocrine Practice. 12 (4): 358–362. doi:10.4158/ep.12.4.358. PMID 16901792.
  25. ↑ Blackburn D, Hux J, Mamdani M (September 2002). "Quantification of the Risk of Corticosteroid-induced Diabetes Mellitus Among the Elderly". Journal of General Internal Medicine. 17 (9): 717–720. doi:10.1046/j.1525-1497.2002.10649.x. PMC 1495107. PMID 12220369.
  26. ↑ Chalitsios CV, Shaw DE, McKeever TM (January 2021). "Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies". Thorax. 76 (1): 21–28. doi:10.1136/thoraxjnl-2020-215664. PMID 33087546. S2CID 224822416.
  27. ↑ Chalitsios CV, McKeever TM, Shaw DE (January 2021). "Incidence of osteoporosis and fragility fractures in asthma: a UK population-based matched cohort study". The European Respiratory Journal. 57 (1). doi:10.1183/13993003.01251-2020. PMID 32764111. S2CID 221078530.
  28. ↑ Chalitsios CV, Shaw DE, McKeever TM (May 2021). "Corticosteroids and bone health in people with asthma: A systematic review and meta-analysis". Respiratory Medicine. 181 106374. doi:10.1016/j.rmed.2021.106374. PMID 33799052. S2CID 232771681.
  29. ↑ Zhang L, Prietsch SO, Ducharme FM (July 2014). "Inhaled corticosteroids in children with persistent asthma: effects on growth". The Cochrane Database of Systematic Reviews. 2014 (7) CD009471. doi:10.1002/14651858.CD009471.pub2. PMC 8407362. PMID 25030198.
  30. ↑ Pecora PG, Kaplan B (1996). "Corticosteroids and ulcers: is there an association?". The Annals of Pharmacotherapy. 30 (7–8): 870–872. doi:10.1177/106002809603000729. PMID 8826575. S2CID 13594804.
  31. ↑ Martínek J, Hlavova K, Zavada F, Seifert B, Rejchrt S, Urban O, Zavoral M (October 2010). ""A surviving myth"--corticosteroids are still considered ulcerogenic by a majority of physicians". Scandinavian Journal of Gastroenterology. 45 (10): 1156–1161. doi:10.3109/00365521.2010.497935. PMID 20569095. S2CID 5140517.
  32. ↑ Abouammoh MA (2015). "Advances in the treatment of central serous chorioretinopathy". Saudi Journal of Ophthalmology. 29 (4): 278–286. doi:10.1016/j.sjopt.2015.01.007. PMC 4625218. PMID 26586979.
  33. ↑ Petzold A, Braithwaite T, van Oosten BW, Balk L, Martinez-Lapiscina EH, Wheeler R, et al. (January 2020). "Case for a new corticosteroid treatment trial in optic neuritis: review of updated evidence". Journal of Neurology, Neurosurgery, and Psychiatry. 91 (1): 9–14. doi:10.1136/jnnp-2019-321653. PMC 6952848. PMID 31740484.
  34. ↑ Fukushima C, Matsuse H, Tomari S, Obase Y, Miyazaki Y, Shimoda T, Kohno S (June 2003). "Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone". Annals of Allergy, Asthma & Immunology. 90 (6): 646–651. doi:10.1016/S1081-1206(10)61870-4. PMID 12839324.
  35. ↑ Shirley DA, Moonah S (July 2016). "Fulminant Amebic Colitis after Corticosteroid Therapy: A Systematic Review". PLOS Neglected Tropical Diseases. 10 (7) e0004879. doi:10.1371/journal.pntd.0004879. PMC 4965027. PMID 27467600.
  36. ↑ Shepard TH, Brent RL, Friedman JM, Jones KL, Miller RK, Moore CA, Polifka JE (April 2002). "Update on new developments in the study of human teratogens". Teratology. 65 (4): 153–161. doi:10.1002/tera.10032. PMID 11948561.
  37. ↑ Nnoruka EN, Daramola OO, Ike SO (2007). "Misuse and abuse of topical steroids: implications". Expert Review of Dermatology. 2 (1): 31–40. doi:10.1586/17469872.2.1.31. Retrieved 2014-12-18.
  38. ↑ Rathi SK, D'Souza P (July 2012). "Rational and ethical use of topical corticosteroids based on safety and efficacy". Indian Journal of Dermatology. 57 (4): 251–259. doi:10.4103/0019-5154.97655. PMC 3401837. PMID 22837556.
  39. ↑ Fukaya M, Sato K, Sato M, Kimata H, Fujisawa S, Dozono H, et al. (2014). "Topical steroid addiction in atopic dermatitis". Drug, Healthcare and Patient Safety. 6: 131–138. doi:10.2147/dhps.s69201. PMC 4207549. PMID 25378953.
  40. ↑ Aljebab F, Choonara I, Conroy S (April 2016). "Systematic review of the toxicity of short-course oral corticosteroids in children". Archives of Disease in Childhood. 101 (4): 365–370. doi:10.1136/archdischild-2015-309522. PMC 4819633. PMID 26768830.
  41. ↑ Galván, César A.; Guarderas, Juan Carlos (September 2012). "Practical Considerations for Dysphonia Caused by Inhaled Corticosteroids". Mayo Clinic Proceedings. 87 (9): 901–904. doi:10.1016/j.mayocp.2012.06.022. PMC 3496982. PMID 22958993.
  42. ↑ Rietschel RL (2007). Fisher's Contact Dermatitis, 6/e. Hamilton, Ont: BC Decker Inc. p. 256. ISBN 978-1-55009-378-0.
  43. ↑ Coopman S, Degreef H, Dooms-Goossens A (July 1989). "Identification of cross-reaction patterns in allergic contact dermatitis from topical corticosteroids". The British Journal of Dermatology. 121 (1): 27–34. doi:10.1111/j.1365-2133.1989.tb01396.x. PMID 2757954. S2CID 40425526.
  44. ↑ Wolverton SE (2001). Comprehensive Dermatologic Drug Therapy. WB Saunders. p. 562.
  45. ↑ "Asthma Steroids: Inhaled Steroids, Side Effects, Benefits, and More". Webmd.com. Retrieved 2012-11-30.
  46. 1 2 3 4 5 6 7 Mayo Clinic Staff (September 2015). "Asthma Medications: Know your options". MayoClinic.org. Retrieved 2018-02-27.
  47. 1 2 "Systemic steroids (corticosteroids). DermNet NZ". . DermNet NZ. 2012-05-19. Retrieved 2012-11-30.
  48. ↑ Khan MO, Park KK, Lee HJ (2005). "Antedrugs: an approach to safer drugs". Current Medicinal Chemistry. 12 (19): 2227–2239. doi:10.2174/0929867054864840. PMID 16178782.
  49. ↑ Calvert DN (August 1962). "Anti-inflammatory steroids". Wisconsin Medical Journal. 61: 403–404. PMID 13875857.
  50. ↑ Alberto Conde-Taboada (2012). Dermatological Treatments. Bentham Science Publishers. pp. 35–36. ISBN 978-1-60805-234-9.
  51. ↑ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1642–1643. ISBN 978-0-8155-1856-3.
  52. ↑ Kim KW, Roh JK, Wee HJ, Kim C (14 November 2016). Cancer Drug Discovery: Science and History. Springer. pp. 169–. ISBN 978-94-024-0844-7.
  53. ↑ Nayak, Surajit; Acharjya, Basanti (December 19, 2008). "Deflazacort versus other glucocorticoids: A comparison". Indian Journal of Dermatology. 53 (4): 167–170. doi:10.4103/0019-5154.44786. PMC 2763756. PMID 19882026.
  54. ↑ Kendall EC (April 1951). "The development of cortisone as a therapeutic agent" (PDF). Antibiotics & Chemotherapy (Northfield, Ill.). 1 (1): 7–15. PMID 24540604. Archived from the original (PDF) on 15 April 2017.
  55. ↑ Buer JK (October 2014). "Origins and impact of the term 'NSAID'". Inflammopharmacology. 22 (5): 263–267. doi:10.1007/s10787-014-0211-2. hdl:10852/45403. PMID 25064056. S2CID 16777111.
  56. ↑ US 2462133, Sarett LH, "Process of Treating Pregnene Compounds", issued 1947
  57. ↑ Marker RE, Wagner RB (September 1947). "Steroidal sapogenins". Journal of the American Chemical Society. 69 (9): 2167–2230. Bibcode:1947JAChS..69.2167M. doi:10.1021/ja01201a032. PMID 20262743.
  58. ↑ Peterson DH, Murray HC (1952). "Microbiological Oxygenation of Steroids at Carbon 11". J. Am. Chem. Soc. 74 (7): 1871–2. Bibcode:1952JAChS..74.1871P. doi:10.1021/ja01127a531.
  59. ↑ US 2752339, Julian L, Cole JW, Meyer EW, Karpel WJ, "Preparation of Cortisone", issued 1956
  60. ↑ "Contact Allergen of the Year: Corticosteroids: Introduction". Medscape.com. 2005-06-13. Retrieved 2012-11-30.