Introduction
Methylprednisolone is a prednisolone derivative glucocorticoid with higher potency than prednisone.
In the outbreak of COVID-19, low dose methylprednisolone-based therapy was successful in treating COVID-19-associated pneumonia in one patient with long-term immunosuppression. The efficacy of methylprednisolone in novel coronavirus pneumonia is being investigated further in clinical trials.
Uses
Methylprednisolone is a corticosteroid used to treat inflammation or immune reactions across a variety of organ systems, endocrine conditions, and neoplastic diseases.
Oral and intramuscular methylprednisolone are indicated for a number of endocrine, rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, gastrointestinal, nervous system, and other disorders. Intra-articular and soft tissue injections are indicated for short term treatment of acute gouty arthritis, acute and subactute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, and synovitis of osteoarthritis. Intralesional injections are indicated for alopecia areata, discoid lupus erythematosus, keloids, lichen planus, lichen simplex chronicus and psoriatic plaques, necrobiosis lipoidica diabeticorum, and localized hypertrophic infiltrated inflammatory lesions of granuloma annulare.
Associated Conditions
Pharmacodynamics
Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Corticosteroids have a wide therapeutic window as patients may 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 methylprednisolone has 89.9% the bioavailability of oral methylprednisolone acetate, while rectal methylprednisolone has 14.2% the bioavailability. Intravitreal methylprednisolone has a Tmax of 2.5h. Approximately 1/10 of an oral or IV dose of methylprednisolone will reach the vitreous humor. Further data regarding the absorption of methylprednisolone are not readily available.
Volume of Distribution
The average volume of distribution of methylprednisolone is 1.38L/kg.
Protein Binding
Methylprednisolone is 76.8% protein bound in plasma and does not significantly bind to corticosteroid binding protein. Methylprednisolone is bound to human serum albumin in plasma.
Route of Elimination
Methylprednisolone and its metabolites have been collected in urine in humans. A study in dogs showed 25-31% elimination in urine and 44-52% elimination in feces.
Half Life
Methylprednisolone has a half life of 2.3h.
Clearance
The average plasma clearance of methylprednisolone is 336mL/h/kg.
Toxicity
The oral LD50 in rats is >4g/kg. The intraperitoneal LD50 in mice is 2292mg/kg and in rats is 100mg/kg.
Data regarding acute overdoses of glucocorticoids are rare. Chronic high doses of glucocorticoids can lead to the development of cataract, glaucoma, hypertension, water retention, hyperlipidemia, peptic ulcer, pancreatitis, myopathy, osteoporosis, mood changes, psychosis, dermal atrophy, allergy, acne, hypertrichosis, immune suppression, decreased resistance to infection, moon face, hyperglycemia, hypocalcemia, hypophosphatemia, metabolic acidosis, growth suppression, and secondary adrenal insufficiency. Treat acute overdoses with symptomatic and supportive therapy, while chronic overdoses will require temporarily reduced dosages.
Food Interactions
- Avoid alcohol.
- Take with food. Food reduces GI irritation.
Dosage
Rheumatoid and Osteoarthritis: The dose for intra-articular administration depends upon the size of the joint and varies with the severity of the condition in the individual patient. The doses in the following table are given as a general guide:
- Large Size of joint (Knees, Ankles, Shoulders): 20 to 80 mg
- Medium Size of joint (Elbows, Wrists): 10 to 40 mg
- Small Size of joint (Metacarpophalangeal, Interphalangeal, Sternoclavicular, Acromioclavicular): 4 to 10 mg.
Dermatological Conditions: 20 to 60mg of the suspension is injected into the lesion. It may be necessary to distribute doses ranging from 20 to 40mg by repeated local injections in the case of large lesions. One to four injections are usually employed, the intervals between injections varying with the type of lesion being treated and the duration of improvement produced by the initial injection.
2. Administration For Systemic Effect: In patients with the adrenogenital syndrome, a single intramuscular injection of 40mg every two weeks may be adequate. For maintenance of patients with rheumatoid arthritis, the weekly intramuscular dose will vary from 40 to 120 mg. The usual dosage for patients with dermatologic lesions benefited by systemic corticoid therapy is 40 to 120 mg of methylprednisolone acetate administered intramuscularly at weekly intervals for one to four weeks. In acute severe dermatitis due to poison ivy, relief may result within 8 to 12 hours following intramuscular administration of a single dose of 80 to 120mg. In chronic contact dermatitis, repeated injections at 5 to 10 day intervals may be necessary. In seborrheic dermatitis, a weekly dose of 80mg may be adequate to control the condition. Following intramuscular administration of 80 to 120 mg to asthmatic patients, relief may result within 6 to 48 hours and persist for several days to two weeks. Similarly in patients with allergic rhinitis (hay fever), an intramuscular dose of 80 to 120mg may be followed by relief of coryzal symptoms within six hours persisting for several days to three weeks.
3. Multiple Sclerosis: In treatment of acute exacerbations of multiple sclerosis, daily doses of 160 mg of methylprednisolone for a week followed by 64mg every other day for 1 month have been shown to be effective (4mg of methylprednisolone is equivalent to 5mg of prednisolone). Or, as directed by the registered physician.
