Methylprednisolone


Article Author:
Antonio Ocejo


Article Editor:
Ricardo Correa


Editors In Chief:
Kranthi Sitammagari
Mayank Singhal


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Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
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Hajira Basit
Phillip Hynes
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Sandeep Sekhon


Updated:
8/21/2019 7:41:34 PM

Indications

Methylprednisolone is a systemic synthetic corticosteroid, which, just as the naturally occurring glucocorticoids, exerts a wide range of physiologic effects. Clinical use of methylprednisolone is mainly due to its anti-inflammatory and immunosuppressive activity in the human body.

Labeled indications of methylprednisolone subcategorize by its use in different organ systems:

  • In dermatology, it has utility in the management of atopic dermatitis,[1] contact dermatitis,[2] pemphigus vulgaris and foliaceus.[3] bullous pemphigus,[4] erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.[5]
  • In endocrinology, it is used in the management of congenital adrenal hyperplasia,[6] hypercalcemia associated with cancer,[7] and as a second-line treatment in conjunction with mineralocorticoids for primary or secondary adrenocortical insufficiency.
  • In gastroenterology, methylprednisolone its use is for acute exacerbations of inflammatory bowel disease.[8]
  • In hematology, it serves in the treatment of autoimmune hemolytic anemia,[9] congenital (erythroid) aplastic anemia,[10] and immune thrombocytopenia.[11]
  • In neurology, it is the mainstay therapy in acute exacerbations of multiple sclerosis.[12]
  • In ophthalmology, it is a therapeutic choice in severe allergic and inflammatory processes of the eye and its adnexa, such as uveitis, scleritis, chorioretinitis, iritis and iridocyclitis, keratitis, optic neuritis, retinal vasculitis, and allergic conjunctivitis.[13]
  • In nephrology, it is helpful in the management of nephrotic syndrome, idiopathic type,[14] or secondary to lupus nephritis.[15]
  • In pulmonology, its indications include aspiration pneumonitis,[16] asthma,[17] chronic beryllium disease, as an adjunct to antituberculous chemotherapy in disseminated pulmonary tuberculosis, in eosinophilic pneumonia,[18] and symptomatic sarcoidosis.[19]
  • In rheumatology, it has indications for the management of acute rheumatic carditis,[20] acute gout,[21] ankylosing spondylitis,[22] dermatomyositis and polymyositis,[23] psoriatic arthritis,[24] and rheumatoid arthritis, including the juvenile type,[25] and systemic lupus erythematosus.[26]

Other miscellaneous labeled indications for methylprednisolone include:

  • Intraarticular and soft tissue administration in acute gouty arthritis, acute and subacute bursitis, acute tenosynovitis, epicondylitis, and synovitis of osteoarthritis.[27][28]
  • Intralesional administration in alopecia areata,[29] discoid lupus erythematosus,[30] keloid disease,[31] and lichen planus.[32]

Off-label indications of methylprednisolone include:

  • Adjunct therapy for acute spinal cord injury
  • Moderate to severe acute distress respiratory syndrome and severe alcoholic hepatitis
  • As a preventive agent in bronchiolitis obliterans syndrome
  • Hormonal resuscitation in cadaveric organ recovery
  • Treatment of acute cellular and antibody-mediated rejection in cardiac transplant
  • Adjunct in the management of acute exacerbation of chronic obstructive pulmonary disease
  • Severe/refractory nausea and vomiting of pregnancy
  • Adjunct treatment of Pneumocystis pneumonia in HIV-infected patients
  • As palliation alternative in castration-resistant metastatic prostate cancer

Mechanism of Action

Methylprednisolone and its derivatives, methylprednisolone acetate succinate, and methylprednisolone sodium, are intermediate-acting, synthetic glucocorticoids used mainly as anti-inflammatory or immunosuppressive agents. Methylprednisolone is five times more potent in its anti-inflammatory properties relative to hydrocortisone (cortisol), with minimal mineralocorticoid activities compared to the latter.[33]

Methylprednisolone diffuses passively across the cellular membrane and binds to the intracellular glucocorticoid receptor. This complex translocates into the nucleus, where it interacts with specific DNA sequences, resulting in either enhancement or suppression of transcription of particular genes. The methylprednisolone-glucocorticoid receptor complex binds and blocks promoter sites of proinflammatory genes,[34] promotes expression of anti-inflammatory gene products,[35] and inhibits the synthesis of inflammatory cytokines, mainly by blocking the function of transcription factors, such as nuclear factor-kappa-B (NF-kB).[36]

Methylprednisolone, like the rest of the corticosteroids, also suppresses the synthesis of cyclooxygenase (COX)-2, responsible for the production of prostaglandins in damaged tissue, leading to the inflammation cascade.[37]

By reversing capillary permeability, suppressing the migration of fibroblasts and polymorphonuclear leukocytes, controlling the rate of protein synthesis, and stabilizing lysosomes, at the cellular level, methylprednisolone may control or prevent inflammation through these actions as well.

Methylprednisolone inhibits cell-mediated immunologic functions, especially those dependent on lymphocytes. Glucocorticoid administration results in a neutrophilic leukocytosis, smaller elevations in monocytes, dramatic reductions in circulating eosinophils, and lesser reductions in lymphocytes. The use of methylprednisolone and other glucocorticoids results in a reduced ability of leukocytes to adhere to vascular endothelium and exit from the circulation. Glucocorticoids impair a variety of T cell functions, and moderate-to-high doses induce T cell apoptosis while keeping B cell function and antibody production preserved.[38]

Tissue-specific responses to steroids can occur by the presence in each tissue of specific protein regulators controlling the interaction between the hormone-receptor complex and particular DNA response elements. This activity leads to a wide array of gene expression and physiological responses by corticosteroids.

Some of the most important effects of methylprednisolone and the rest of the corticosteroids are the result of homeostatic responses by insulin and glucagon. Glucocorticoids stimulate gluconeogenesis, which results in elevated blood glucose, catabolism of muscle protein, and stimulation of insulin secretion. Both lipolysis and lipogenesis become stimulated, with a net increase of fat deposition in certain areas (e.g., face, shoulders, and back).[39]

Methylprednisolone and the rest of the glucocorticoids cause muscle protein catabolism. Also, lymphoid and connective tissue, fat, and skin undergo wasting under the influence of high concentrations of these steroids. Catabolic effects on the bone can lead to osteoporosis. In children, growth inhibition takes place.

Administration

Methylprednisolone may be administered orally with food or milk to decrease gastrointestinal adverse effects. Administration may also be intramuscularly or intravenously. When administered intramuscularly (in the form of methylprednisolone acetate or succinate), administration should not be into the deltoid muscle due to evidence of subcutaneous atrophy. Injections into the dermis should be avoided, and injection should not be into areas that have evidence of acute local infection.

Intravenous administration of methylprednisolone (in the form of methylprednisolone succinate) is rate dependent upon the dose and severity of the condition. Most commonly, with intermittent infusion, methylprednisolone is administered over 15 to 60 minutes. The administration of large doses should be over at least 30 to 60 minutes. 

There are reports of hypotension, cardiac arrhythmias, and sudden death when methylprednisolone administration occurs under 30 minutes in doses greater or equal than 250 mg.[40]

The onset of action of intravenous methylprednisolone succinate is within 1 hour, while intra-articular administration of IV acetate is of 1 week, with a duration of 1 to 5 weeks. Methylprednisolone has an oral bioavailability of 88% approximately. The half-life elimination of intravenous methylprednisolone is of 0.25 hours, with an oral half-life of 2-5 hours. It has hepatic metabolism and undergoes urinary excretion.[41][42]

Adverse Effects

The significant undesirable effects of glucocorticoids result from their hormonal actions, which lead to the clinical picture of iatrogenic Cushing syndrome. Facial rounding, puffiness, fat deposition, and plethora usually appear (moon facies). Fat tends to redistribute from the extremities to the trunk, the back of the neck, and the supraclavicular fossae. There is increased growth of fine hair on the face, thighs, and trunk.  Steroid-induced punctate acne may appear, and insomnia and increased appetite are also effects.

With concurrent use of methylprednisolone, protein catabolism will continue, diverting amino acids to glucose production, thus increasing the need for insulin and over time resulting in weight gain. Myopathy and muscle wasting can occur, as well as thinning of the skin, with striae and bruising. Hyperglycemia and eventually osteoporosis can develop, as well as diabetes and aseptic necrosis of the hip.[43]

A more detailed way to review the adverse effects of methylprednisolone and other corticosteroids is by classifying them based on the different organ systems affected:

  • Dermatologic and side effects in appearance include skin thinning and ecchymoses, Cushingoid features, and weight gain.
  • Ophthalmologic side effects include the formation of cataracts, the increase of intraocular pressure, and the development of exophthalmos.
  • Cardiovascular side effects include fluid retention and hypertension, premature atherosclerotic disease, arrhythmias, and possible hyperlipidemia.
  • Gastrointestinal effects include the increased risk of gastritis, ulcer formation, and gastrointestinal bleeding. 
  • Bone and muscle effects include osteoporosis, osteonecrosis, and myopathy.
  • Neuropsychiatric side effects include mood disorders, psychosis, and memory impairment.
  • Metabolic and endocrine side effects consist of hyperglycemia and hypothalamic-pituitary-adrenal axis suppression.
  • Immune system effects include increased susceptibility of infections.
  • Hematologic side effects include leukocytosis and neutrophilia.

Contraindications

Methylprednisolone contraindications include patients with documented hypersensitivity to the drug or components, systemic fungal infection, intrathecal administration, live or attenuated virus vaccine, idiopathic thrombocytopenia purpura, or in premature infants.[44]

Methylprednisolone, like all other glucocorticoids, must be used with great caution in patients with peptic ulcer, heart disease or hypertension with heart failure, certain infectious illnesses such as varicella and tuberculosis, psychoses, diabetes, osteoporosis, or glaucoma.[45]

Monitoring

Blood pressure, blood glucose, electrolytes, weight, bone mineral density, HPA hypothalamic-pituitary-adrenal (HPA) axis suppression, and intraocular pressure all require monitoring in patients taking methylprednisolone. Growth and development monitoring should be in place for children.

Patients receiving methylprednisolone must be monitored carefully for the development of hyperglycemia, glycosuria, sodium retention with edema or hypertension, hypokalemia, peptic ulcer, osteoporosis, and hidden infections.

The dosage should be as low as possible. Even patients maintained on low doses of methylprednisolone may require supplementary therapy at times of stress, such as during surgery, intercurrent illness, or trauma occurs.

Toxicity

Most of the toxic effects of methylprednisolone and other glucocorticoids are predictable from their impact on the body's physiology. Some are life-threatening and include metabolic effects (growth inhibition, diabetes, muscle wasting, osteoporosis), salt retention (although less common with methylprednisolone), and psychosis.

Methods for minimizing these toxicities include local application, alternate-day therapy (to reduce pituitary suppression), and tapering the dose promptly after attaining a therapeutic response. To prevent adrenal insufficiency in patients who have received long-term treatment with methylprednisolone, additional "stress doses" may be necessary during serious illness or before major surgery.

Enhancing Healthcare Team Outcomes

Methylprednisolone is a widely-used drug in multiple fields of medicine, mainly due to its anti-inflammatory and immunosuppressive properties. Healthcare workers including nurses, pharmacists, and clinicians should be aware of its broad spectrum of clinical applications, both labeled and off-labeled indications; while keeping into consideration its contraindications and individualizing its use based on the patient's comorbidities and tolerance of side effects. Of particular importance, patients receiving methylprednisolone should undergo monitoring for the development of hyperglycemia, hypertension, peptic ulcer, osteoporosis, and hidden infections.

Physicians (MDs, DOs, NPs, PAs) will be prescribing or ordering the medication. Nursing will administer if inpatient, and can monitor for adverse effects in both inpatient and outpatient settings. Pharmacists should be involved to verify dosing and perform medication reconciliation. Both pharmacists and nurses need to alert the healthcare team if they encounter any issues of concern. All these members of the interprofessional healthcare team need to communicate and collaborate across interdisciplinary lines to ensure optimal therapeutic results. [Level V]

As with all glucocorticoids, methylprednisolone's adverse effects are both dose- and duration-dependent and can range from non-serious displeasing appearance to those that are life-threatening. Interprofessional coordination and care between healthcare workers are needed to ensure that methylprednisolone dosage remains at a minimum for the shortest period necessary to achieve the treatment goals. Preexisting comorbidities that may become exacerbated when treated with methylprednisolone require management, and that patients under treatment are monitored for adverse effects, identifying who may benefit from additional intervention.


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Methylprednisolone - Questions

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What is the highest cumulative dose of intravenous methylprednisolone for a 12-week course of treatment that is considered safe?



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A 74-year-old female previously diagnosed with rheumatoid arthritis presents to the emergency department with bilateral shoulder pain, left knee pain, and right ankle pain of 3 days of onset. On physical examination, both shoulders are tender, swollen, and warm to the touch, as well as her left knee and right ankle. She is found to have painful vasculitis in her fingertips and the palms of both hands. Which of the following medications would be most beneficial for this patient at the moment?



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A 65-year-old male with a past medical history of left renal transplant 2 months ago secondary to acute polycystic kidney disease is referred from his nephrology clinic to the emergency department due to fever, malaise, oliguria and an acute rise in serum creatinine. He reports that he has not adhered to his immunosuppressive therapy. After a renal biopsy is reviewed, the diagnosis is made for T cell-mediated acute renal allograft rejection. Treatment is initiated with IV methylprednisolone pulses with plans on oral glucocorticoid taper afterward. What complications can the patient develop if the high doses of methylprednisolone are infused in less than 30 minutes?



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A 65-year-old homeless male with a past medical history of multiple asthma exacerbations is admitted to the ICU with hypotension, fever, wheezing, and shortness of breath. Laboratory tests show leukocytosis, hypokalemia, and hyponatremia. The sepsis treatment protocol is initiated along with respiratory support and treatment for his asthma exacerbation. He shows no improvement after 2 days of broad-spectrum antibiotic therapy. On his third day of hospital stay, blood cultures grow Candida albicans. Which of the following is a contraindication for the use of methylprednisolone in this patient?



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A 65-year-old female with a past medical history of open-angle glaucoma comes to the emergency department with a 3-day history of the left arm and leg numbness. She had an episode of trigeminal neuralgia 3 years ago that responded to abortive treatment. On physical examination, sensation to light touch and pinprick is diminished on the left side. MRI of the brain and spinal cord shows hyperintense lesions in the periventricular area and some areas of the spinal cord. IV methylprednisolone is started after she is diagnosed with acute multiple sclerosis exacerbation. Which of the following parameters needs to be monitored in this patient after methylprednisolone infusion?



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A 65-year-old female admitted due to acute hypoxic respiratory failure secondary to extensive interstitial lung disease (IDL) and heart failure exacerbation is currently being treated with furosemide and supplemental oxygen as needed. She was previously treated with oral corticosteroids for her IDL. CT scan of the chest is performed and showed an extensive honey-combing pattern in both lungs. As her shortness of breath and cough do not significantly improve with aggressive diuretic therapy, the decision is made to start IV methylprednisolone to decrease lung parenchyma inflammation. The next day, the patient is found to be anxious, restless and reporting seeing animals roam around her room. What is the most likely cause of this patient's visual hallucinations?



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Methylprednisolone - References

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Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of PA-Hospital Medicine. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for PA-Hospital Medicine, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in PA-Hospital Medicine, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of PA-Hospital Medicine. When it is time for the PA-Hospital Medicine board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study PA-Hospital Medicine.