Introduction
Prednisolone is a glucocorticoid similar to cortisol used for its anti-inflammatory, immunosuppressive, anti-neoplastic, and vasoconstrictive effects.
Uses
Prednisolone is a glucocorticoid used to treat adrenocortical insufficiency, inflammatory conditions, and some cancers.
Prednisolone is indicated to treat endocrine, rheumatic, and hematologic disorders; collagen, dermatologic, ophthalmic, respiratory, and gastrointestinal diseases; allergic and edematous states; and other conditions like tuberculous meningitis.
Associated Conditions
Pharmacodynamics
Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Prednisolone has a short duration of action as the half life is 2.1-3.5 hours. Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.
Mechanism of Action
The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.
Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.
Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.
Absorption
Oral prednisolone reaches a Cmax of 113-1343ng/mL with a Tmax of 1.0-2.6 hours. Oral prednisolone is approximately 70% bioavailable.
Volume of Distribution
A 0.15mg/kg dose of prednisolone has a volume of distribution of 29.3L, while a 0.30mg/kg dose has a volume of distribution of 44.2L.
Protein Binding
Prednisolone's protein binding is highly variable, ranging from 65-91% in healthy patients.
Route of Elimination
Prednisolone is over 98% eliminated in urine.
Half Life
Prednisolone has a plasma half life of 2.1-3.5 hours. This half life is shorter in children and longer in those with liver disease.
Clearance
A 0.15mg/kg dose of prednisolone has a clearance of 0.09L/kg/h, while a 0.30mg/kg dose has a clearance of 0.12L/kg/h.
Toxicity
The intraperitoneal LD50 in rats is 2g/kg and 65mg/kg in mice. The subcutaneous LD50 in rats is 147mg/kg and >3500mg/kg in mice. The oral LD50 in mice is 1680mg/kg. In humans, the oral TDLO in men is 9mg/kg/2W and in women is 14mg/kg/13D.
Patients experiencing an overdose of prednisolone may present with gastrointestinal disturbances, insomnia, and restlessness. Overdose of oral prednisolone may be treated by gastric lavage or inducing vomiting if the overdose was recent, as well as supportive and symptomatic therapy. Chronic overdosage may be treated by dose reduction or treating patients on alternate days. An overdose by the ophthalmic route is not expected to cause problems.
Food Interactions
- Avoid alcohol.
- Take with food. Food reduces irritation.
Dosage
Nephrotic Syndrome:
- Initial: 2 mg/kg/day (maximum 80 mg/day) in divided doses 3 to 4 times/day until urine is protein free for 3 consecutive days (maximum: 28 days); followed by 1 to 1.5 mg/kg/dose given every other day for 4 weeks.
- Maintenance dose: 0.5 to 1 mg/kg/ dose given every other day for 3 to 6 months.
Acute Asthma: 40-60 mg/day PO in single daily dose or divided q12 hr for 3-10 days.
Allergic Conditions:
- Day 1: 10 mg PO before breakfast, 5 mg after lunch and after dinner, and 10 mg at bedtime.
- Day 2: 5 mg PO before breakfast, after lunch, and after dinner and 10 mg at bedtime.
- Day 3: 5 mg PO before breakfast, after lunch, after dinner, and at bedtime.
- Day 4: 5 mg PO before breakfast, after lunch, and at bedtime.
- Day 5: 5 mg PO before breakfast and at bedtime.
- Day 6: 5 mg PO before breakfast.
Pediatric-
Asthma:
- 1 year: Acute: 10 mg orally every 12 hours. Maintenance: 10 mg orally every other day.
- 1 to 4 years: Acute: 20 mg orally every 12 hours. Maintenance: 20 mg orally every other day.
- 5 to 12 years: Acute: 30 mg orally every 12 hours. Maintenance: 30 mg orally every other day.
- 12 years: Acute: 40 mg orally every 12 hours. Maintenance: 40 mg orally every other day.
Immunosuppression: 0.05 to 2 mg/kg/day divided 1 to 4 times/day.
