Prednisolone

Prednisolone is a steroid medication used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers.[5][6] Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arthritis, dermatitis, eye inflammation, asthma, and multiple sclerosis.[6] It can be taken by mouth, injected into a vein, used topically as a skin cream, or as eye drops.[7][8][6]

Not to be confused with Prednisone.

Prednisolone
Clinical data
Trade namesOrapred, PediaPred, Millipred, others
Other names11,17-Dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydrocyclopenta[a] phenanthren-3-one
AHFS/Drugs.comMonograph
MedlinePlusa615042
License data
Pregnancy
category
Routes of
administration		By mouth, intravenous, topical, eye drop
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life2–3.5 hours[2][3][4]
Excretionurine
Identifiers
IUPAC name
  • (11β)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.020
Chemical and physical data
FormulaC21H28O5
Molar mass360.450 g·mol−1
3D model (JSmol)
  • O=C\1\C=C/[C@]4(/C(=C/1)CC[C@@H]2[C@@H]4[C@@H](O)C[C@@]3([C@@](O)(C(=O)CO)CC[C@@H]23)C)C
  • InChI=1S/C21H28O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h5,7,9,14-16,18,22,24,26H,3-4,6,8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1 Y
  • Key:OIGNJSKKLXVSLS-VWUMJDOOSA-N Y
  (verify)

Side effects with short-term use include nausea and feeling tired.[5] More severe side effects include psychiatric problems, which may occur in about 5% of people.[9] Common side effects with long term use include bone loss, weakness, yeast infections, and easy bruising.[6] While short-term use in the later part of pregnancy is safe, long-term use or use in early pregnancy is occasionally associated with harm to the baby.[1] It is a glucocorticoid made from hydrocortisone (cortisol).[10]

Prednisolone was discovered and approved for medical use in 1955.[10] It is on the World Health Organization's List of Essential Medicines.[11] It is available as a generic medication.[6] In 2019, it was the 139th most commonly prescribed medication in the United States, with more than 4 million prescriptions.[12][13]

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[14] such as asthma,[15] uveitis, pyoderma gangrenosum, rheumatoid arthritis, urticaria,[16] angioedema,[16] ulcerative colitis, pericarditis, temporal arteritis and Crohn's disease, Bell's palsy, multiple sclerosis,[17] cluster headaches, vasculitis, acute lymphoblastic leukemia and autoimmune hepatitis,[18] systemic lupus erythematosus, Kawasaki disease,[19] dermatomyositis,[7] and sarcoidosis.[20]

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.[21][8][22] It has been explored as a treatment option for bacterial keratitis.[23]

Prednisolone can also be used for allergic reactions ranging from seasonal allergies to drug allergic reactions.[24]

Prednisolone can also be used as an immunosuppressive drug for organ transplants.[7][25]

Prednisolone in lower doses can be used in cases of primary adrenal insufficiency (Addison's disease).[26][27]

Corticosteroids inhibit the inflammatory response to a variety of inciting agents and, it is presumed, delay or slow healing.[28] They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation with inflammation.[29]

Adverse effects

Adverse reactions from the use of prednisolone include:[30][7]

  • Increased appetite, weight gain, nausea, and malaise
  • Increased risk of infection
  • Cardiovascular events
  • Dermatological effects including reddening of face, bruising/skin discoloration, impaired wound healing, thinning of skin, skin rash, fluid build up and abnormal hair growth
  • Hyperglycemia; patients with diabetes may need increased insulin or diabetic therapies
  • Menstrual abnormalities
  • Lower response to hormones, especially during stressful instances such as surgery or illness
  • Change in electrolytes: rise in blood pressure, increased sodium and low potassium, leading to alkalosis
  • GI system effects: swelling of stomach lining, reversible increase in liver enzymes, and risk of stomach ulcers
  • Muscular and skeletal abnormalities, such as muscle weakness/muscle loss, osteoporosis (see steroid-induced osteoporosis), long bone fractures, tendon rupture, and back fractures
  • Neurological effects, including involuntary movements (convulsions), headaches, and vertigo
  • Behavioral disturbances[31]
  • Nasal septum perforation and bowel perforation (in some pathologic conditions).[32][33]

Withdrawal from prednisolone after long-term or high-dose use can lead to adrenal insufficiency.[31]

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.[31]

Pharmacology

As a glucocorticoid, the lipophilic structure of prednisolone 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 blocks the transcription of inflammatory genes.[34]

Chemistry

Prednisolone is a synthetic pregnane corticosteroid closely related to its cognate prednisone, having identical structure save for two fewer hydrogens near C11. It is also known as δ1-cortisol, δ1-hydrocortisone, 1,2-dehydrocortisol, or 1,2-dehydrohydrocortisone, as well as 11β,17α,21-trihydroxypregna-1,4-diene-3,20-dione.[35][36]

Society and culture

Dosage forms

In the United States:

  • Prednisolone sodium phosphate oral solution (Pediapred)[31]
  • Prednisolone acetate oral suspension (Flo-Pred)[30]
  • Prednisolone oral tablets (Millipred)[24]
  • Prednisolone sodium phosphate oral dissolving tablets (Orapred ODT)[7]
  • Prednisolone acetate ophthalmic suspension (Omnipred, Pred Forte)[8][21][22]

Athletics

As a glucocorticosteroid, unauthorized or ad hoc use of prednisolone during competition via oral, intravenous, intramuscular or rectal routes is banned under World Anti-Doping Agency (WADA) anti-doping rules.[37]

Veterinary uses

Prednisolone is used in the treatment of inflammatory and allergic conditions in cats, dogs, horses, small mammals such as ferrets, birds, and reptiles. Its usage in treating inflammation, immune-mediated disease, Addison’s disease, and neoplasia is often ‘off label’ or ‘extra label’. Many drugs are commonly prescribed for off label use in veterinary medicine."[38] Studies in ruminating species, such as alpacas, have shown that oral administration of the drug is associated with a reduced bioavailability compared to intravenous administration, however, levels that are therapeutic in other species can be achieved with oral administration in alpacas.[39]

See also

References
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  2. Pickup ME (1979). "Clinical pharmacokinetics of prednisone and prednisolone". Clinical Pharmacokinetics. 4 (2): 111–28. doi:10.2165/00003088-197904020-00004. PMID 378499. S2CID 12218704.
  3. Bergrem H, Grøttum P, Rugstad HE (1983). "Pharmacokinetics and protein binding of prednisolone after oral and intravenous administration". European Journal of Clinical Pharmacology. 24 (3): 415–9. doi:10.1007/BF00610064. PMID 6861855. S2CID 33189235.
  4. Bashar T, Apu MN, Mostaid MS, Islam MS, Hasnat A (2018). "Pharmacokinetics and Bioavailability Study of a Prednisolone Tablet as a Single Oral Dose in Bangladeshi Healthy Volunteers". Dose-response. 16 (3): 1559325818783932. doi:10.1177/1559325818783932. PMC 6073839. PMID 30083083.
  5. World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. pp. 53–54. hdl:10665/44053. ISBN 9789241547659.
  6. "Prednisolone". The American Society of Health-System Pharmacists. Archived from the original on 23 December 2016. Retrieved 8 December 2016.
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  9. "Pevanti 10mg Tablets – Summary of Product Characteristics (SPC) – (eMC)". www.medicines.org.uk. 1 December 2014. Archived from the original on 20 December 2016. Retrieved 13 December 2016.
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  • US patent 2837464, Arthur Nobile, "Process for production of dienes by corynebacteria", published 1958-06-03, issued 1958-06-03, assigned to SCHERING CORP
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