<!-- Definition, medical uses, and side effects -->
Methylprednisolone, sold under the brand name Medrol among others, is a synthetic glucocorticoid, primarily prescribed for its anti-inflammatory and immunosuppressive effects. It is either used at low doses for chronic illnesses or used at high doses during acute flares. Methylprednisolone and its derivatives can be administered orally or parenterally.
Regardless of the route of administration, methylprednisolone integrates systemically as exhibited by its effectiveness to quickly reduce inflammation during acute flares. It is associated with many adverse reactions that require tapering off the drug as soon as the disease is under control. Serious side effects include iatrogenic Cushing's syndrome, hypertension, osteoporosis, diabetes, infection, psychosis, and skin atrophy. In 2023, it was the 135th most commonly prescribed medication in the United States, with more than 4 million prescriptions. It is on the World Health Organization's List of Essential Medicines.
Medical uses
The primary use of methylprednisolone is to suppress inflammatory and immune responses. Methylprednisolone achieves this primarily by regulating the number and function of leukocytes, cytokines, and chemokines. The National Asthma Education and Prevention Program (NAEPP) indicates systemic methylprednisolone in both short- and long-term therapies to quickly control and to suppress persistent asthma, respectively. For exacerbations that result in a visit to the emergency department (ED), oral methylprednisolone is preferred over intravenous administration, unless there are issues with adherence or vomiting. Oral methylprednisolone is less invasive and studies have shown equivalent efficacy to intravenous methylprednisolone. In lupus nephritis, a common manifestation of SLE, patients are often prescribed methylprednisolone concomitantly with immunosuppressants. Severe manifestations are often treated with cyclophosphamide or rituximab and three doses of methylprednisolone IV-pulse treatment (as recommended by ACR guidelines) before switching to oral prednisolone and azathioprine for maintenance. It is most commonly injected into the joints of the knees and shoulders.
Primary or secondary adrenocortical insufficiency
Methylprednisolone is not typically recommended for primary or secondary adrenocortical insufficiency compared to other corticosteroids which have a higher affinity for mineralocorticoid receptors and salt-retaining properties. The prevalence varies from 1.3 to 62% of adult treated patients. Clinical features of Cushing's syndrome are inclusive of many adverse effects in glucocorticoid therapy. The World Health Organization (WHO) defines osteoporosis in caucasian postmenopausal women as a bone mineral density (BMD) and a T-score of -2.5 or less. The prevalence of osteoporosis in patients with SLE varies geographically and some attribute it to BMD and T-score diagnostic appropriateness. Prolonged suppression leads to inadequate responses to physical and emotional stresses, such as illness and trauma. Abrupt termination of the drug commonly causes transient non-specific symptoms such as loss of appetite, abdominal pain, vomiting, drowsiness, confusion, headache, fever, joint and muscle pain, peeling skin, and weight loss. However, there was a wide range of prevalence and lack of uniformity in the follow-up timeline. The now active methylprednisolone-GR complex can either transduce non-genomic changes in the cytoplasm or translocate to the nucleus and regulate the transcriptional activity of target genes by direct, tethering or composite mechanisms. PTMs modulate many functions including nuclear translocation, strength and duration of receptor signaling and cofactor interaction. These mechanisms are characterized as having a rapid onset (less than 15 minutes) because they do not rely on time-consuming transcription or translation and are not modified by inhibitors of transcription.
Methylprednisolone-induced non-genomic signaling is classified by three mechanisms: (1) cytoplasmic glucocorticoid receptor (cGR)-mediated non-genomic effects, (2) membrane-bound glucocorticoid receptor (mGR) non-genomic effects, and (3) physiochemical interactions with cellular membranes (non-specific non-genomic effects). It is evidence that dissociated SRC is responsible for inhibiting the release of arachidonic acid (AA) from cell membrane phospholipids. Both methylprednisolone acetate (Depo-Medrol) and methylprednisolone succinate (Solu-Medrol) are approved for intramuscular injection. Depo-Medrol is additionally approved for intralesional, intra-articular, and soft tissue injections. Depo-Medrol is available as sterile aqueous solution in 20 mg/mL, 40 mg/mL, or 80 mg/mL strengths. In contrast to endogenous GCs, methylprednisolone does not bind to the glycoprotein transcortin (corticosteroid-binding globulin, CBG) but does have moderate protein binding to albumin.
Methylprednisolone is primarily eliminated by hepatic metabolism and renal excretion of metabolites; with renal excretion of unchanged methylprednisolone at only 1.3–9.2%. Methylprednisolone acetate suspension (Depo-Medrol) is a 6-methyl derivative of prednisolone that melts at 215 degrees Celsius with some decomposition. A variety of methylprednisolone esters with differing characteristics exist and have been marketed for medical use.