Prednisolone

Adverse effects

Adverse reactions from the use of prednisolone include:

• Increased appetite, weight gain,
• nausea,
• malaise,
• Increased risk of infection
• Cardiovascular events
• Dermatological effects including reddening of the face, bruising/skin discoloration, impaired wound healing, skin atrophy, skin rash, edema, 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
• Gastrointestinal system effects: swelling of the 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
• Psychosocial behavioral and emotional disturbances with aggression being one of the most common cognitive symptoms, especially with oral use.
• Nasal septum perforation and bowel perforation (in some pathologic conditions).

Discontinuing prednisolone after long-term or high-dose use can lead to adrenal insufficiency.

Mania and hypomania are known possible side effects of prednisolone.

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 increased likelihood of cleft palate.

Prednisolone is found in the breast milk of mothers taking prednisolone.

Local adverse effects in the eye

When used topically on the eye, the following are potential side effects:

• Cataracts: Extended usage of corticosteroids may cause clouding at the back of the lens, also known as posterior subcapsular cataract. This type of cataract reduces the path of light reaching the eye, which interferes with a person's reading vision. Consumption of prednisolone eye drops post-surgery may also retard the healing process.
• Corneal thinning: When corticosteroids are used in the long term, corneal and scleral thinning is also one of the consequences. When not ceased, thinning may ultimately lead to perforation of the cornea.
• Glaucoma: Prolonged use of corticosteroids has a chance of causing a raised intraocular pressure (IOP), injuring the optic nerve and weakening visual awareness. Corticosteroids should be used cautiously in patients with concomitant conditions of glaucoma. Doctors track patients' IOP if they are using corticosteroid eye drops for more than 103 days.

Pharmacology

Pharmacodynamics

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, the 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 the synthesis of anti-inflammatory proteins while binding to negative GREs blocks the transcription of inflammatory genes. They inhibit the release of signals that promote inflammation such as nuclear factor-Kappa B (NF-κB), Activator protein 1 (AP-1), nuclear factor of activated T-cells (NFAT), and stimulate anti-inflammatory signals such as the interleukin-10 gene. All of them will collectively cause a sequence of events, including the inhibition of prostaglandin synthesis and additional inflammatory mediators. Glucocorticoids also inhibit neutrophil cell death and demargination. As well as phospholipase A2, which in turn lessens arachidonic acid derivative genesis.

Pharmacokinetics

Prednisolone has a relatively short half-life, ranging 2–4 hours. It also has a large therapeutic window, considering the dosage required to produce a therapeutic effect is a few times higher than what the body naturally produces.

Prednisolone is 70–90% plasma protein bound, it binds to proteins such as albumin.

Both prednisolone phosphate and prednisolone acetate go through ester hydrolysis in the body to form prednisolone. It subsequently undergoes the usual metabolism of prednisolone. Concomitant use of prednisolone and strong CYP3A4 inhibitors such as ketoconazole is shown to cause a rise in plasma prednisolone concentrations by about 50% owing to a diminished clearance.

Prednisolone predominantly undergoes kidney elimination and is excreted in the urine as sulphate and metabolites of glucuronide conjugate.

Prednisone

Prednisone is a prodrug that is activated in the liver. When it enters the body, prednisone is triggered by the liver and body chemicals to turn into its active form, prednisolone.

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.

Interactions

Co-administration of prednisolone eye drops with ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) may perhaps exacerbate its effects, causing unwanted side effects such as toxicity. The wound healing process may also be hindered.

Drug interactions of prednisolone include other immunosuppressants like azathioprine or ciclosporin, antiplatelet drugs like clopidogrel, anticoagulants like dabigatran or warfarin, or NSAIDs such as aspirin, celecoxib, or ibuprofen.

Special populations

Children

Prolonged use of prednisolone eye drops in children may lead to raised intraocular pressure. While this phenomenon is dose-dependent, it is shown to have a greater effect, especially in children under 6 years of age.

Pregnancy and breastfeeding

Research on animal reproduction has indicated that there is a trace of teratogenicity when doses are reduced by 10 times the human recommended dose. There is no sufficient information on human pregnancy at this moment. Use is only recommended when the potential benefits outweigh the potential risks for the pregnant mother and the fetus.

Prednisolone when delivered systemically can be found in the mother's breast milk, however, there is no data provided for the extent of prednisolone found in the system after administering eye drops. However, the presence of corticosteroids is recorded when they are administered systemically, and it could affect the fetus' growth. Therefore, the use of prednisolone during breastfeeding is not advocated.

Society and culture

Dosage forms

Prednisolone is supplied as oral liquid, oral suspension, oral syrup, oral tablet, and oral disintegrating tablet. It may be a generic medication or supplied as brands Flo-Pred (prednisolone acetate oral suspension), Millipred (oral tablets), Orapred (prednisolone sodium phosphate oral dissolving tablets), Pediapred (prednisolone sodium phosphate oral solution), Veripred 20, Prelone, Hydeltra-T.B.A., Hydeltrasol, Key-Pred, Cotolone, Predicort, Medicort, Predcor, Bubbli-Pred, Omnipred, P-Pred (prednisolone acetate ophthalmic suspension), Pred Mild, Pred Forte, and others.

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.

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 considered off-label use. Many drugs are commonly prescribed for off-label use in veterinary medicine." 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.

It is used in a broad spectrum of diseases, for example, inflammation of scleral tissues, cornea, and conjunctiva in dogs. In horses, prednisolone acetate suspensions are priorly used to treat inflammation in the middle layer of the eye, also known as anterior uveitis and equine recurrent uveitis (ERU), which is the leading cause of visual impairment in horses. Prednisolone acetate eye drops are not to be used in other animals such as birds.

Prednisolone acetate eye drops are also prescribed to dogs and cats to lessen swelling, redness, burning, and pain sensations after surgeries of the eye.

Cats with conjunctivitis usually are required to avoid using ophthalmic preparations of corticosteroids and its derivatives. The most typical infections are caused by herpes virus.