Prednisolone

Not to be confused with Prednisone.
Prednisolone
Systematic (IUPAC) name
(11β)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682794
License data
Pregnancy
category
  • AU: A
  • US: C (Risk not ruled out)
Legal status
Legal status
Pharmacokinetic data
Biological half-life 2-3 hours
Excretion urine
Identifiers
CAS Number 50-24-8 YesY
ATC code A07EA01 (WHO) C05AA04 (WHO), D07AA03 (WHO), H02AB06 (WHO), R01AD02 (WHO), S01BA04 (WHO), S02BA03 (WHO), S03BA02 (WHO)
PubChem CID 5755
IUPHAR/BPS 2866
DrugBank DB00860 YesY
ChemSpider 5552 YesY
UNII 9PHQ9Y1OLM YesY
KEGG D00472 YesY
ChEBI CHEBI:8378 YesY
ChEMBL CHEMBL131 YesY
Synonyms 11,17-Dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydrocyclopenta[a] phenanthren-3-one
Chemical data
Formula C21H28O5
Molar mass 360.444 g/mol
  (verify)

Prednisolone is a synthetic glucocorticoid, a derivative of cortisol, used to treat a variety of inflammatory and autoimmune conditions and some cancers. It is the active metabolite of the drug prednisone[1] and is used especially in patients with liver failure, as these individuals are unable to metabolize prednisone into active prednisolone; it is primarily metabolized via the liver enzyme, 11-β-hydroxydehydrogenase.[2] Adverse effects are not generally seen with short term therapy, but weight gain, impaired immune response, and behavioral disturbances commonly occur with longer durations of treatment.[2]

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[3]

Medical uses

Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and autoimmune conditions[4] such as asthma,[5] uveitis, pyoderma gangrenosum, rheumatoid arthritis, ulcerative colitis, pericarditis, temporal arteritis and Crohn's disease, Bell's palsy, multiple sclerosis,[6] cluster headaches, vasculitis, acute lymphoblastic leukemia and autoimmune hepatitis,[7] systemic lupus erythematosus, Kawasaki disease,[8] dermatomyositis,[9] and sarcoidosis.[10]

Prednisolone acetate ophthalmic suspension (eye drops) is an adrenocortical steroid product, prepared as a sterile ophthalmic suspension and used to reduce swelling, redness, itching, and allergic reactions affecting the eye.[11][12]

Prednisolone can also be used for allergic reactions ranging from seasonal allergies to drug allergic reactions.[13]

Prednisolone can also be used as an immunosuppressive drug for organ transplants.[9][14]

Prednisolone in lower doses can be used in cases of primary adrenal insufficiency (Addison's disease).[15][16]

Corticosteroids inhibit the inflammatory response to a variety of inciting agents and, it is presumed, delay or slow healing.[17] They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation with inflammation.[18]

Adverse effects

There are several adverse reaction from the use of prednisolone:

Nasal septum perforation and bowel perforation are also notable adverse effects that restrict steroids' use in some pathologic conditions.[20][21]

Withdrawal from prednisolone after long term or high dose use can lead to adrenal insufficiency.[19]

Pregnancy and breastfeeding

Although there are no major human studies of prednisolone use in pregnant women, studies in several animals show that it may cause birth defects including increase cleft palate. Prednisolone should be used in pregnant women when benefits outweigh the risks and children born from mothers using prednisolone during pregnancy should be monitored for impaired adrenal function.

Prednisolone is found in breast milk of mothers taking prednisolone.[19]

Mechanism of action

As a synthetic glucocorticoid (GC), its lipophilic structure allows for easy passage through the cell membrane where it then binds to its respective glucocorticoid receptor (GCR) located in the cytoplasm. Upon binding, formation of the GC/GCR complex causes dissociation of chaperone proteins from the glucocorticoid receptor enabling the GC/GCR complex to translocate inside the nucleus. This process occurs within 20 minutes of binding. Once inside the nucleus, the homodimer GC/GCR complex binds to specific DNA binding-sites known as glucocorticoid response elements (GREs) resulting in gene expression or inhibition. Complex binding to positive GREs leads to synthesis of anti-inflammatory proteins while binding to negative GREs block the transcription of inflammatory genes.[22]

Society and culture

Dosage forms

In the United States

Athletics

As a glucocorticosteroid, unauthorized or ad-hoc use of prednisolone during competition via oral, intravenous, intramuscular or rectal routes is banned under WADA anti-doping rules.[25] The drug may be used in competition with a TUE (Therapeutic Use Exemption), in compliance with WADA regulations. Local or topical use of prednisolone during competition as well as any use out of competition is not regulated.[25]

See also

References

  1. ↑ Davis M, Williams R, Chakraborty J, et al. (June 1978). "Prednisone or prednisolone for the treatment of chronic active hepatitis? A comparison of plasma availability". British Journal of Clinical Pharmacology 5 (6): 501–5. doi:10.1111/j.1365-2125.1978.tb01664.x. PMC 1429358. PMID 656293.
  2. 1 2 Frey, Brigitte (March 1985). "Pharmacokinetics of 3 prednisolone prodrugs. Evidence of therapeutic inequivalence in renal transplant patients with rejection.". Transplantation 39: 270–4. doi:10.1160/TH11-09-0672. PMID 3883592.
  3. ↑ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
  4. ↑ Czock D, Keller F, Rasche FM, Häussler U (2005). "Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids". Clin Pharmacokinet 44 (1): 61–98. doi:10.2165/00003088-200544010-00003. PMID 15634032.
  5. ↑ Fiel SB, Vincken W (Jun 2006). "Systemic corticosteroid therapy for acute asthma exacerbations". J Asthma 43 (5): 321–31. doi:10.1080/02770900600567163. PMID 16801135.
  6. ↑ Thrower BW (Jan 2009). "Relapse management in multiple sclerosis". Neurologist 15 (1): 1–5. doi:10.1097/NRL.0b013e31817acf1a. PMID 19131851.
  7. ↑ Lambrou GI, Vlahopoulos S, Papathanasiou C, Papanikolaou M, Karpusas M, Zoumakis E, Tzortzatou-Stathopoulou F (2009). "Prednisolone exerts late mitogenic and biphasic effects on resistant acute lymphoblastic leukemia cells: Relation to early gene expression". Leuk Res. 33 (12): 1684–95. doi:10.1016/j.leukres.2009.04.018. PMID 19450877.
  8. ↑ Miura M, Tamame T, Naganuma T, Chinen S, Matsuoka M, Ohki H (2011). "Steroid pulse therapy for Kawasaki disease unresponsive to additional immunoglobulin therapy". Paediatrics & Child Health 16 (8): 479–84. PMC 3202387. PMID 23024586.
  9. 1 2 Product Information: ORAPRED ODT(TM) orally disintegrating tablets, prednisolone sodium phosphate orally disintegrating tablets. Cima Labs Inc, Alpharetta, GA, 2006.
  10. ↑ Gera, Kamal; Gupta, Nitesh; Ahuja, Anuradha; Shah, Ashok (2014-04-30). "Acute alveolar sarcoidosis presenting with hypoxaemic respiratory failure". BMJ Case Reports 2014: bcr2013202247. doi:10.1136/bcr-2013-202247. ISSN 1757-790X. PMC 4024548. PMID 24789154.
  11. ↑ "Pred Forte Package Insert" (PDF).
  12. ↑ Product Information: OMNIPRED(TM) ophthalmic suspension, prednisolone acetate ophthalmic suspension. Alcon Laboratories Inc, Fort Worth, TX, 2005
  13. 1 2 "Millipred tablets package insert" (PDF).
  14. ↑ Vethe, Nils; Midtvedt, Karsten; Åsberg, Anders; Amundsen, Rune; Bergan, Stein. "Legemiddelinteraksjoner og immunsuppresjon hos organtransplanterte". Tidsskrift for Den norske legeforening 131 (20): 2000–2003. doi:10.4045/tidsskr.11.0138.
  15. ↑ Husebye, E. S.; Allolio, B.; Arlt, W.; Badenhoop, K.; Bensing, S.; Betterle, C.; Falorni, A.; Gan, E. H.; Hulting, A.-L. (2014-02-01). "Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency". Journal of Internal Medicine 275 (2): 104–115. doi:10.1111/joim.12162. ISSN 1365-2796.
  16. ↑ AMA Department of Drugs: AMA Drug Evaluations, 6th. American Medical Association, Chicago, IL, 1986.
  17. ↑ Schwiebert, L. M.; Beck, L. A.; Stellato, C.; Bickel, C. A.; Bochner, B. S.; Schleimer, R. P.; Schwiebert, L. A. (1996-01-01). "Glucocorticosteroid inhibition of cytokine production: relevance to antiallergic actions". The Journal of Allergy and Clinical Immunology 97 (1 Pt 2): 143–152. doi:10.1016/s0091-6749(96)80214-4. ISSN 0091-6749. PMID 8568145.
  18. ↑ Lee, Sang Hag (2015). "Mechanisms of Glucocorticoid Action in Chronic Rhinosinusitis". Allergy, Asthma & Immunology Research 7 (6): 534–7. doi:10.4168/aair.2015.7.6.534. PMC 4605925. PMID 26333699.
  19. 1 2 3 4 "PEDIAPRED" (PDF).
  20. ↑ "Bowel Perforation in Steroid-Treated Patients"
  21. ↑ "Intranasal steroids and septum perforation--an overlooked complication?"
  22. ↑ Stahn, Cindy (17 May 2007). "Molecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists" (PDF). Molecular and Cellular Endocrinology 275: 71–78. doi:10.1016/j.mce.2007.05.019.
  23. ↑ "Flo-Pred Package Insert" (PDF).
  24. ↑ "Package Insert for Orapred ODT" (PDF).
  25. 1 2 "The 2011 Prohibited List".
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