July/August 2014

Steroid-Related Risks
By Mark D. Coggins, PharmD, CGP, FASCP
Today’s Geriatric Medicine
Vol. 7 No. 4 P. 8

Glucocorticoids (GCs), often referred to as corticosteroids, systemic steroids, or steroids, primarily are synthetic, biologically active derivatives of the cortisol secreted by the adrenal cortex. They should not be confused with muscle-building anabolic steroids (eg, testosterone).

The effects of GCs are widespread and include alterations in carbohydrates (increased blood glucose levels), stimulation of amino acid release, maintenance of fluid and electrolyte balance, preservation of normal cardiovascular system function, immune system suppression, and decreased bone formation.

Indications
GCs possess potent anti-inflammatory properties and are used to treat a variety of inflammatory and autoimmune disorders, placing them among the most frequently prescribed classes of drugs. In the United States, GCs are prescribed to 1 million patients per year, with approximately 2.5% of patients between the ages of 70 and 79 estimated as using them.1

Conditions commonly treated with steroids include asthma; arthritis (eg, rheumatoid arthritis); autoimmune disorders such as irritable bowel syndrome, lupus, and multiple sclerosis; skin conditions such as eczema and rashes; some types of cancer; and Addison’s disease (insufficient cortisol production) as well as the prevention of organ rejection in transplant recipients.2

Steroid Formulations
The American Academy of Allergy, Asthma, and Immunology website provides useful online drug guides that include information on many of the most commonly available steroid products and formulations (www.aaaai.org/conditions-and-treatments/drug-guide.aspx).

Oral formulations of steroids, such as prednisone (Deltasone), prednisolone (Prelone), dexamethasone (Decadron), and methylprednisolone (Medrol), typically are used to treat inflammation and pain associated with chronic conditions such as rheumatoid arthritis and lupus.3

Some steroids formulated for injection or IV infusion include methylprednisolone (Solu-Medrol) and dexamethasone (Dexasone). Steroids also may be injected directly into affected joints to reduce inflammation (synovitis). A long-acting steroid, such as triamcinolone hexacetonide (Aristocort), often is used for intra-articular steroid injections.3

Inhaled steroids often are used to help control inflammation associated with asthma. Patients should be educated on proper inhaler technique to maximize therapeutic effects and minimize local side effects, including oral candidiasis (thrush) and dysponia (hoarseness). Patients can use a spacer or holding chamber with inhalers and should be advised to rinse their mouths after each use to reduce the amount of inhaled steroid deposited in the mouth and throat.

Nasal steroids such as fluticasone propionate (Flonase), mometasone furoate monohydrate (Nasonex), and triamcinolone acetonide (Nasacort AQ), are widely used for nasal allergies. Proper administration technique is essential because failing to use intranasal corticosteroids correctly can lead to nasal septum perforation. The medication must be sprayed away from the nasal septum, and trauma to nasal mucosa from the canister’s delivery tip should be avoided. These drug administration concerns may be problematic when dealing with frail and cognitively impaired older adults.4

Topical steroid formulations are used to treat numerous skin conditions and vary widely in their potency.5

Dosing Equivalencies and Length of Therapy
The beneficial effects of GCs as well as their potential for side effects are proportional to the dose administered. In general, doses of individual steroids are classified as being low dose (7.5 mg/day or less), medium dose (between 7.5 and 30 mg/day), or high dose (greater than 30 mg/day).6 Steroid doses often are described in terms of equivalent doses of prednisone (eg, 5 mg of prednisone is equivalent to 4 mg of methylprednisolone) and also in terms of their duration of action, such as short, intermediate, or long acting. (This table from the University of Missouri Kansas City provides additional information: http://med.umkc.edu/docs/em/Corticosteroid_Table.pdf.)

Short-term GC treatment typically lasts fewer than one to three months. Treatment extending longer than three months is considered long term and results in the majority of severe side effects. When steroids are used for short durations of a few days or weeks, they are relatively safe. It is important for patients to be informed of the risks associated with steroid therapy, with prescribers giving careful consideration to assessing the expected benefits vs. the associated risks.

Steroid-Associated Risks
• Adrenal suppression: Adrenal suppression refers to the body’s inability to produce sufficient cortisol following exposure to high-dose or long-term GC use. Longer-acting GC formulations tend to be associated with a higher risk of adrenal suppression. Systemic absorption of inhaled, topical, and intraocular GCs also may cause adrenal suppression. Morning administration may be less suppressive than evening administration, and alternate day therapy may help reduce adrenal suppression. Patients should be slowly titrated off GCs to help reduce the negative effects of adrenal suppression.2

Signs of adrenal syndrome include weakness/fatigue, malaise, nausea, vomiting, diarrhea, abdominal pain, headache (usually in the morning), fever, anorexia/weight loss, myalgia, arthralgia, and psychiatric symptoms. Signs of adrenal crisis include hypotension, decreased consciousness, lethargy, unexplained hypoglycemia, hyponatremia, seizure, and coma.2

• Weight gain and fat redistribution: Almost all patients taking GCs long term will experience weight gain that may be accompanied by fluid retention and the redistribution of fat from the arms and legs to the face (moon face), back of the neck (buffalo hump), and stomach (truncal obesity).2 Patients should be encouraged to exercise and limit caloric intake to help minimize weight gain.

• Wound healing: Long-term use of steroids may impair wound healing in susceptible individuals. Patients receiving steroids who are at risk of impaired wound healing (eg, pressure ulcers) may benefit from supplementation with vitamin A, which can improve wound healing and counteract some of the negative effects of corticosteroids on skin integrity.7

• Increased blood glucose and diabetes: Patients with existing diabetes who are receiving steroids may experience high blood glucose levels resulting in the need for adjustment of diabetes medications. Additionally, nondiabetic patients receiving higher daily doses of steroids can experience transient or persistent diabetes requiring treatment. Postprandial blood sugars appear to be impacted more significantly than fasting blood sugars. In general, steroid-induced hyperglycemia improves with dose reductions and resolves when steroid therapy is discontinued, although some patients may develop persistent diabetes.2

• Cataracts and glaucoma: The risk of both cataracts and glaucoma is increased in patients using GCs, and this risk appears to be dose dependent. Routine eye examinations are recommended.2

• Atherosclerosis and cardiovascular risk: Patients taking chronic steroids are at increased risk of mortality as a result of atherosclerosis due to increased cholesterol, very low and low density lipoproteins, and reduced cardioprotective high density lipoproteins. These factors lead to increased risk of ischemic heart disease, including angina, heart failure, myocardial infarcts, cerebrovascular accident, and transient ischemic attacks.

Fluid balance is altered with long-term steroid use, causing edema and weight gain. Older patients and other patients at risk of heart or kidney disease are susceptible to sodium and fluid retention, which may lead to hypertension and congestive heart failure. Potassium loss also may occur, causing general weakness.2,8

Increased blood pressure is common, especially with higher doses of steroids (more than 10 mg of prednisone or equivalent daily dose).

• Gastrointestinal ulcers and bleeding: Steroid use increases the risk of gastritis and peptic ulcers, and this risk significantly increases when steroids are taken with NSAIDs such as ibuprofen, aspirin, or naproxen. Patients should be advised to take acid-lowering medications such as proton pump inhibitors or H2 blockers and should take steroids with a meal to help reduce stomach irritation. Patients should call their physician immediately if they experience any severe persisting abdominal pain or black, tarry stools.2

• Mental status changes: Corticosteroids can induce numerous psychiatric and mental status changes, including depression, delirium, psychosis, and mania, which may require assessment and treatment. Patients may experience mood swings, increased energy, excitement, and euphoria.2

• Decreased immune response: GCs reduce the effects of T cells, B cells, phagocytes, and cytokines, which are involved in immune response. While this makes GCs effective for controlling a wide range of inflammatory diseases, it also leads to increased susceptibility to infections, especially when high doses are used. Patients may experience increased white blood cell counts due to an increase in circulating neutrophils and may have reduced efficacy and increased risk from live vaccines. However, routine immunizations such as annual influenza vaccinations are safe and recommended.2

• Osteoporosis, fractures, and osteonecrosis: A meta-analysis of more than 80 studies in adults found the use of prednisolone (or equivalent) to be associated with significant reductions in bone mineral density and an increase in fracture risk within three to six months of initiation. An examination of 42,500 patients from seven prospectively reviewed cohort studies found that corticosteroid use increased fracture risk in both adult men and women, regardless of bone mineral density and prior fracture history.2

Osteonecrosis (bone death) develops in between 9% and 40% of adult patients receiving long-term GC therapy, whether from systemic therapy or via intra-articular injections. In one epidemiological study, the fracture risk increased even at low doses of prednisolone (2.5 mg and equivalent doses). Another study demonstrated a significant increase in the risk of vertebral fractures. In patients receiving 10 mg of prednisolone (or its equivalent) daily for three months, the risk of hip fractures increased sevenfold, with the increase of lumbar spine fractures increased by 17-fold.2

To help prevent osteoporosis, the American College of Rheumatology recommends the following2:

• reduce GC dose and therapy duration to the minimum that is clinically effective for specific diseases;

• engage in regular physical activity, including body-weight exercises;

• prevent falls;

• stop smoking;

• limit alcohol intake;

• increase calcium intake to 1,200 to 1,500 mg/day; and

• take a preventive dose of 800 to 1,000 IU/day of vitamin D.

Patients on chronic steroid treatment may require much higher doses of vitamin D3 (cholecaliferol), such as 50,000 IU monthly.

Patients at the highest risk of fractures should be considered for bisphosphonate therapy (eg, alendronate, risedronate, zoledronate). Patients receive the most benefit from bisphosphonate treatment when started at the same time steroid therapy is initiated because most bone loss occurs within the first few months of therapy.

Recommended Monitoring
Monitoring recommendations for GC treatment vary depending on the duration of treatment and dose intensity. Recommended baseline monitoring includes serum glucose, lipid profile, and bone mineral density. After treatment begins, blood pressure, weight gain, visual changes, shortness of breath, edema, and polydipsia (excessive thirst) also should be checked during each physician visit. Additionally, if chronic long-term treatment with steroids is used, bone mineral density should be monitored at least yearly.2

— Mark D. Coggins, PharmD, CGP, FASCP, is a director of pharmacy services for more than 300 skilled nursing centers operated by Golden Living and a director on the board of the American Society of Consultant Pharmacists. He was recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

References
1. Sewerynek E, Stuss M. Steroid-induced osteoporosis. Aging Health. 2012;8(5):471-477.

2. Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30.

3. Glucocorticoids (steroids). RheumatoidArthritis.net website. http://www.rheumatoidarthritis.net/treatment/steroids. Accessed June 4, 2014.

4. Sastre J, Mosges R. Local and systemic safety of intranasal corticosteroids. J Investig Allergol Clin Immunol. 2012;22(1):1-12.

5. Basics of topical corticosteroids. National Eczema Association website. http://nationaleczema.org/eczema/treatment/topical-corticosteroids/basics-of-topical-corticosteroids. Accessed June 2, 2014

6. Steroids. The Johns Hopkins Lupus Center website. http://www.hopkinslupus.org/lupus-treatment/lupus-medications/steroids. Accessed June 1, 2014

7. Wang AS, Armstrong EJ, Armstrong AW. Corticosteroids and wound healing: clinical considerations in the perioperative period. Am J Surg. 2013;206(3):410-417.

8. Ruyssen-Witrand A, Fautrel B.,Saraux A, Le Loët X, Pham T. Cardiovascular risk induced by low-dose corticosteroids in rheumatoid arthritis: A systematic literature review. Joint Bone Spine. 2011;78(1):23-30.