Topical prednisolone
# Topical prednisolone

Topical prednisolone is a type of glucocorticoid, mainly used in the ophthalmic pathway as eye drops in numerous eye conditions, such as corneal injuries caused by chemicals, burns and alien objects, inflammation of the eyes, mild to moderate non-infectious allergies, disorders of the eyelid, conjunctiva or sclera, ocular inflammation caused by operation and optic neuritis. Some side effects include glaucoma, blurring of vision, eye discomfort, impaired recovery of injured site, scarring of the optic nerve, clouding of lenses and urticaria. However, their prevalence is not known.

Prednisolone eye drops are contraindicated in individuals who develop hypersensitivity reactions against prednisolone, or individuals with the current conditions, such as tuberculosis of the eye, shingles affecting the eye, raised intraocular pressure, eye infection caused by fungus, diabetes.

Prednisolone eye drops can be either formulated in solutions or suspensions. Solutions, in general, have better performance than suspensions regardless of the amount of time shaken, as suspensions fail to dispense the same amount of corticosteroids each time. Suspension forms are less suitable for corticosteroid delivery into the eye.

The effects of prednisolone may be greater when used in children under 6 years of age. Women who are pregnant are not recommended to consume this product unless the benefits outweigh the risk. Those who are breastfeeding are not suggested to use this product since there is insufficient evidence to prove its safeness. Individuals who are wearing contact lenses should remove them before administering the eye drop.

## Medical uses

Topical prednisolone are normally formulated as sodium phosphate and acetates.

Prednisolone eye drops are used in conjunctiva inflammations, also known as conjunctivitis, caused by allergies and bacteria, marginal keratitis, inflammation of the anterior segment of the eye, choroid and iris. Endophthalmitis, which is an infection of the eye involving the aqueous humor, Graves' Ophthalmopathy, Herpes Zoster ocular infection, inflammation of the eye after surgery, corneal injuries caused by chemicals, radiations and thermal burns, or penetration of foreign objects. It is also used in the prevention of myringosclerosis,Herpes Simplex Stromal Keratitis. Topical prednisolone can also be used after procedures such as Laser Peripheral Iridotomy for patients with primary angle-closure suspects (PACS) to control infalmmations.

Topical corticosteroids are usually administered for once or twice a day. In spite of that, there are no significant differences in efficacy if administered twice, besides, it may increase the systemic exposure to the drug.

Patient's intraocular pressure should be monitored if they are receiving long term ophthalmic treatments.

No dosage reduction is indicated in patients with kidney and hepatic impairment.

In addition, topical prednisolone can also be administered as ear drops.

Examples of Topical Prednisolone Products :

| Eye Drops | Ear Drops |
| - | - |
| Prednisolone Sodium Phosphate Ophthalmic Solution | Prednisolone Sodium Phosphate 0.5% eye/ ear drops |
| Pred Forte Ophthalmic Suspension (Prednisolone acetate ophthalmic suspension) | Prednisolone Sodium Phosphate 0.5% eye/ ear drops |
| Suspension (Prednisolone Mild Ophthalmic) | Prednisolone Sodium Phosphate 0.5% eye/ ear drops |
| Suspension (Prednisolone Acetate Ophthalmic) | Prednisolone Sodium Phosphate 0.5% eye/ ear drops |

### Other information

Prednisolone eye drops should not be shared between individuals under any circumstances.

If a dose is missed, it is recommended to use it as soon as possible. However, if it is almost time to administer another dose, the missed dose should be omitted. A regular dose should be used at all times, regardless of a missed dose. You should never double a dose to make up for the missed dose.

## Mechanism of Action

Once the eye drops are applied, corticosteroids will bind to their target receptors which are located in the cytoplasm of the cell, subsequently being transported into the cell nucleus. The target receptors of corticosteroids are the glucocorticoid receptors (GRs), 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.

When used in low doses, corticosteroids serve as an anti-inflammatory agent. At higher doses, they are considered as immunosuppressives.

## Pharmacodynamics

Prednisolone has a relatively short duration of action, since its half life ranges from 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 renal elimination and is excreted in the urine as sulphate and metabolites of glucuronide conjugate.

## Adverse effects

### Systemic adverse effects

* Immunosuppression: When used at high doses, corticosteroids also act as immunosuppressants. Prolonged use of corticosteroids may increase the risk of encountering secondary infections and may mask symptoms of acute infections such as fungal infections, or lengthen and aggravate infections caused by viruses.
* Systemic absorption: Researches have revealed that ophthalmically administered corticosteroids will be absorbed into the bloodstream by the body, hence being present in the systemic circulation. Which may cause a reduced production of endogenous corticosteroids. Systemic immunosuppression is ought to be advised to patients in long term topical ophthalmic treatment.

### Local adverse 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 from reaching the eye, which interferes with your 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 its consequences. When not ceased, thinning may ultimately lead to perforation of the cornea.
* Glaucoma: Elongated use of corticosteroids has a chance of causing a raised intraocular pressure (IOP), injuring the optic nerve and weakening of visual awareness. Corticosteroids should be used cautiously in patients with concomitant conditions of glaucoma. We should keep track of patients' IOP if they are using corticosteroid eye drops for more than 103 days.

## Contraindications and drug reactions

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

Some drugs may cause an increased risk of certain side effects, for example, aspirin, estradiol, ethinyl estradiol, rifampin.

Patients with the following conditions should notify their physician as it may affect their use of Topical prednisolone:

* Asthma - asthma attacks may be triggered by prednisolone eye drops that contain sulfite.
* Varicella (chicken pox) eye infection.

## Special populations

### Children use

Prolonged use of prednisolone eye drops in children may lead to a 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

Researches on animal reproduction have indicated that there is a trace of teratogenicity when doses are reduced by 10 times of 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 of 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 possibly affect the fetus' growth. Therefore, use of prednisolone during breastfeeding is not advocated.

### Individuals with contact lenses

Individuals who wear contact lenses should be cautious when using formulations that contain acetate and benzalkonium chloride since the contact lenses may absorb the ingredients mentioned above. Hence, contact lenses should be removed prior to administering the eye drops, and you should wait for at least 15 minutes before wearing them again.

## Veterinary use

Prednisolone acetate suspensions are mainly used in small animals such as dogs, cats and large animals like horses. It is used in a broad spectrum of diseases, for example, inflammation of scleral tissues, cornea, 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 the 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.

