Continuing Education Activity

Prednisone is a synthetic, anti-inflammatory glucocorticoid that derives from cortisone. It is biologically inert and converted to prednisolone in the liver. Prednisone is an FDA-approved, delayed-release corticosteroid indicated as an anti-inflammatory or immunosuppressive agent to treat a broad range of diseases, including immunosuppressive/endocrine, rheumatic, collagen, dermatologic, allergic states, ophthalmic, respiratory, hematologic, neoplastic, edematous, gastrointestinal, acute exacerbations of multiple sclerosis, and as an anti-inflammatory and an antineoplastic agent. Prednisone is a corticosteroid (cortisone-like medicine or steroid). It works on the immune system to help relieve swelling, redness, itching, and allergic reactions. This activity will also highlight the mechanism of action, adverse event profile, and other key factors (e.g., dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the interprofessional team who are involved in the administration of prednisone to patients.

Objectives:

• Identify the mechanism of action of prednisone.
• Summarize the approved and off-label indications for prednisone.
• Outline the contraindications for using prednisone.
• Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients who can benefit from therapy with prednisone.

Indications

Prednisone is a synthetic, anti-inflammatory glucocorticoid that derives from cortisone. It is biologically inert and converted to prednisolone in the liver. Prednisone is an FDA-approved, delayed-release corticosteroid indicated as an anti-inflammatory or immunosuppressive agent to treat a broad range of diseases, including immunosuppressive/endocrine, rheumatic, collagen, dermatologic, allergic states, ophthalmic, respiratory, hematologic, neoplastic, edematous, gastrointestinal (GI, acute exacerbations of multiple sclerosis, and as an anti-inflammatory and an antineoplastic agent. Prednisone is a corticosteroid (cortisone-like medicine or steroid). It works on the immune system to help relieve swelling, redness, itching, and allergic reactions. This medication is available only by prescription.[1]

It is common for prednisone to be prescribed for other indications or in a different dosage than shown in the label information. These are called off-label prescribing or non-FDA-approved indications. Other countries may mention "approved" or "licensed" indications that do not apply in the United States.[2]

Mechanism of Action

Prednisone decreases inflammation via suppression of the migration of polymorphonuclear leukocytes and reversing increased capillary permeability. It also suppresses the immune system by reducing the activity and the volume of the immune system. The antineoplastic effects may correlate with the inhibition of glucose transport, phosphorylation, or induction of cell death in immature lymphocytes. It may have antiemetic effects by blocking the cerebral innervation of the emetic center via inhibition of prostaglandin.

Prednisone is a prodrug to prednisolone, which mediates its glucocorticoid effects. Prednisone is a synthetic glucocorticoid that has both anti-inflammatory and immunomodulating properties. 

After cell surface receptor attachment and entry into the cell, prednisone enters the nucleus, binds, and activates specific nuclear receptors, resulting in altered gene expression and inhibition of proinflammatory cytokine production. This agent decreases the number of circulating lymphocytes, inducing cell differentiation, and stimulates apoptosis in sensitive tumor cell populations.

The effects of glucocorticoids are subject to mediation by mechanisms that alter DNA replication within the nucleus.

Administration

Prednisone may be administered orally with food or milk to decrease gastrointestinal upset. Maximal adrenal cortex activity occurs between 2:00 AM and 8:00 AM, and it is minimal between 4:00 PM and midnight. Exogenous corticosteroids suppress endogenous adrenocortical activity the least when administered during the time of maximal activity (the morning) for single-dose administration. Therefore, recommendations are that prednisone administration takes place in the morning before 9:00 AM, and when administering large doses, the patient should use antacids between meals to help prevent peptic ulcers. Multiple-dose therapy should have an even dose distribution in evenly spaced intervals throughout the day. Antacids also may be administered between meals to help prevent peptic ulcers.[3]

The delayed-release tablets should be swallowed whole without breaking, dividing, crushing, or chewing. The administration of the oral solution should be with the provided calibrated dropper only. Other forms of steroids may be available if the oral formulation is not well-tolerated, for example, intramuscularly (IM), or subcutaneously (SQ). Depending on the disease process, topical steroids may also be an option. It is best to take this medicine with food. Swallow the medication whole. Store the medicine in a tightly closed container at room temperature, away from heat, moisture, and direct light. Do not freeze the oral liquid. Other routes of administration include liquid, solution, syrup, tablet, delayed-release tablets, nasal, rectal, injection, and intravenous.

Ask a patient if they are taking the following medications: aminoglutethimide, amphotericin B, carbamazepine, cholestyramine, cyclosporine, digoxin, isoniazid, ketoconazole, phenobarbital, phenytoin, or rifampin, a blood thinner (such as warfarin), NSAID pain or arthritis medicine (such as aspirin, diclofenac, ibuprofen, naproxen celecoxib), diuretic (water pill), diabetes medicine, a macrolide antibiotic (such as azithromycin, clarithromycin, erythromycin), estrogen (including birth control pills or hormone replacement therapy).

Adverse Effects

The primary adverse effects of prednisone include hyperglycemia, insomnia, increased appetite, hypertension, osteoporosis, edema, adrenal suppression, cataracts, and delayed wound healing.

Adverse effects are common in patients receiving glucocorticoids in high doses or over a long period. High-dose prednisone is 40 mg/d or more. Potential adverse effects include skin fragility, weight gain, increased risk of infections, and fractures. Significant cardiovascular and metabolic effects are hypertension, hyperglycemia, and dyslipidemia.[4]

Other adverse reactions include adrenal insufficiency, particularly when undergoing stressful procedures or during sepsis; this is typically diagnosable when the patient is hypotensive and not responsive to fluids, vasopressors, or cardiogenic medications. Once suspicion of adrenal insufficiency exists, treatment should be administered right away with a dose of 100 mg of hydrocortisone every eight hours. 

Patients on high doses of glucocorticoids for 5 days or more should be tapered off the medication.

Contraindications

Prednisone is contraindicated in patients with documented hypersensitivity to the drug or components of the formulation. Contraindications to the administration of prednisone include the presence of systemic fungal infections.[5] Administering live or live-attenuated vaccines is also contraindicated with the administration of immunosuppressive prednisone doses.

Monitoring

It is essential to monitor for allergic reactions (itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing), dark freckles, skin color changes, coldness, weakness, tiredness, nausea, vomiting, weight loss, rapid weight gain, depression, unusual thoughts, feelings, or behaviors, trouble sleeping, fever, chills, cough, sore throat, and body aches, muscle pain or weakness, swelling in your hands, ankles, or feet, severe stomach pain, red or black stools, skin changes or growths, trouble seeing, eye pain, or headache.

Clinicians must monitor patients with giant cell arteritis because increased cumulative glucocorticoid exposure was associated with an increased risk of glucocorticoid-related adverse effects.[6]

Doctors can opt to track serum glucose, blood pressure, electrolytes, weight, bone mineral density, hemoglobin, occult blood loss, growth in pediatric patients, and infections. The HPA axis suppression should also undergo an assessment by morning cortisol test, adrenocorticotropic hormone stimulation test, and by measuring urinary free cortisol test.

When monitoring, it is essential to remember that the elimination half-life of prednisone is 3 to 4 hours in adults and 1 to 2 hours in children.

More common symptoms to monitor are aggression, agitation, blurred vision, a decrease in the amount of urine, dizziness, irregular heartbeat or pulse, headache, irritability, mood changes, irregular breathing, numbness or tingling in the arms or legs, pounding in the ears, shortness of breath, swelling of the fingers, hands, feet, or lower legs, trouble thinking, speaking, or walking, difficulty with breathing at rest, or weight gain.

Toxicity

Like any anti-inflammatory agent, steroid toxicity is treated similarly to any non-steroidal anti-inflammatory drug overdose or toxicity. Although the frequency of life-threatening complications from steroids and NSAID overdose is low, the overdose response ranges from no symptoms to death despite intensive-care treatment. Most symptoms are an excess of the pharmacological action of steroids and NSAIDs and include abdominal pain, nausea, vomiting, drowsiness, dizziness, headache, ear ringing, and nystagmus. A significant dose-response relationship occurs with the long-term use of systemic corticosteroids and the development of systemic corticosteroid-related complications for patients with severe asthma, resulting in an increased burden and costs on the health care system.[7]

Enhancing Healthcare Team Outcomes

Managing drug adverse effects requires an interprofessional team of healthcare professionals, including a nurse, laboratory technologists, pharmacists, and several physicians in different specialties. Without proper management, the adverse effects of prednisone overdose are high. Systemic corticosteroids have extensive use in the treatment of a variety of autoimmune and inflammatory disorders. Prolonged use, especially at high doses of 40 mg/day, can cause serious adverse effects. The most common systems involved include musculoskeletal, endocrine, cardiovascular, and central nervous system (CNS) and gastrointestinal (GI) tract. Prednisone's side effects can be minimized by monitoring the patient and putting preventative measures in place. Some of these preventative measures include using lower potency dosages and starting patients on the lowest effective dosage per guidelines. The patient needs to be informed of the adverse effects so they may understand and be aware of making the proper lifestyle modifications to help reduce the risk of adverse effects. Patients should receive counsel to seek medical attention if they experience any of these known adverse effects. A steroid treatment card can be recommended to show to all healthcare professionals involved in their care and management. Adults versus children monitoring and care should be noted, particularly regarding growth curve complications, adrenal suppression, and osteoporosis.[8]

To accomplish the above, interprofessional collaboration is crucial. Clinicians prescribe the drug and need to inform the patients about the adverse event profile; this is often the task of the nursing staff. They can also assess patient compliance and let the prescribing clinician know about any possible issues. Pharmacists can counsel the patient on proper administration, as well as reinforce the adverse events. Pharmacists must also perform medication reconciliation and report to the prescribing office regarding any potential interactions. Only through this type of interprofessional communication can prednisone therapy achieve its optimal results. [Level 5]

Review Questions

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References

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Bunte K, Smith DJ, Chappell MJ, Hassan-Smith ZK, Tomlinson JW, Arlt W, Tiňo P. Learning pharmacokinetic models for in vivo glucocorticoid activation. J Theor Biol. 2018 Oct 14;455:222-231. [PubMed: 30048717]

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Puckett Y, Zhang K, Blasingame J, Lorenzana J, Parameswaran S, Brooks Md Facs SE, Baronia BC, Griswold J. Safest Time to Resume Oral Anticoagulation in Patients with Traumatic Brain Injury. Cureus. 2018 Jul 03;10(7):e2920. [PMC free article: PMC6122643] [PubMed: 30186725]

4.

Bergmann TK, Barraclough KA, Lee KJ, Staatz CE. Clinical pharmacokinetics and pharmacodynamics of prednisolone and prednisone in solid organ transplantation. Clin Pharmacokinet. 2012 Nov;51(11):711-41. [PubMed: 23018468]

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Ryu RJ, Easterling TR, Caritis SN, Venkataramanan R, Umans JG, Ahmed MS, Clark S, Kantrowitz-Gordon I, Hays K, Bennett B, Honaker MT, Thummel KE, Shen DD, Hebert MF. Prednisone Pharmacokinetics During Pregnancy and Lactation. J Clin Pharmacol. 2018 Sep;58(9):1223-1232. [PMC free article: PMC6310475] [PubMed: 29733485]

6.

Gale S, Wilson JC, Chia J, Trinh H, Tuckwell K, Collinson N, Dimonaco S, Jick S, Meier C, Mohan SV, Sarsour K. Risk Associated with Cumulative Oral Glucocorticoid Use in Patients with Giant Cell Arteritis in Real-World Databases from the USA and UK. Rheumatol Ther. 2018 Dec;5(2):327-340. [PMC free article: PMC6251855] [PubMed: 29752705]

7.

Dalal AA, Duh MS, Gozalo L, Robitaille MN, Albers F, Yancey S, Ortega H, Forshag M, Lin X, Lefebvre P. Dose-Response Relationship Between Long-Term Systemic Corticosteroid Use and Related Complications in Patients with Severe Asthma. J Manag Care Spec Pharm. 2016 Jul;22(7):833-47. [PMC free article: PMC10397753] [PubMed: 27348284]

8.

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Disclosure: Yana Puckett declares no relevant financial relationships with ineligible companies.

Disclosure: Aishah Gabbar declares no relevant financial relationships with ineligible companies.

Disclosure: Abdullah Bokhari declares no relevant financial relationships with ineligible companies.