184: Glucocorticoids Flashcards
What are the three main mechanisms of glucocorticoid action?
- Direct effects on gene expression: Glucocorticoid receptors bind to glucocorticoid-responsive elements, inducing proteins like annexin I and MAPK phosphatase, which reduce phospholipase A2 activity and limit prostaglandin and leukotriene formation.
- Indirect effects on gene expression: Glucocorticoid receptors interact with other transcription factors, inhibiting AP-1 and nuclear factor κB, which decreases the synthesis of proinflammatory molecules such as cytokines and interleukins.
- Receptor-mediated effects on second messenger cascades: This involves nongenomic pathways like the phosphatidylinositol 3′-kinase (PI3K)-Akt-eNOS pathway.
What are the cellular side effects of corticosteroids?
- Monocytopenia, eosinopenia, and lymphocytopenia: Greater effect on T cells than B cells.
- Lymphocytopenia: Caused by redistribution of cells to other lymphoid tissues.
- Increase in circulating polymorphonuclear leukocytes: Related to demargination from the bone marrow.
- Decreased macrophage functions: Including phagocytosis and antigen processing, affecting hypersensitivity responses.
- Suppression of monocyte and lymphocyte function: More than polymorphonuclear leukocyte function, clinically significant in granulomatous diseases.
What are the indications for glucocorticoid use in dermatology?
Short courses of glucocorticoids may be used for:
- Contact dermatitis
- Atopic dermatitis
- Photodermatitis
- Exfoliative dermatitis
- Erythrodermas
The use of glucocorticoids is controversial in treating:
- Erythema nodosum
- Lichen planus
- Cutaneous T-cell lymphoma
- Discoid lupus erythematosus.
What factors determine the dosing regimen for systemic glucocorticoids?
The dosing regimen for systemic glucocorticoids is determined by:
1. Nature of the disease: The specific condition being treated.
2. Extent of the disease: Severity and spread of the lesions.
3. Route of administration: Options include intralesional, oral, intramuscular, and intravenous.
What risks should be considered when prescribing glucocorticoids to a patient with granulomatous tuberculosis?
Glucocorticoids suppress monocyte and lymphocyte function, increasing the risk of exacerbation and relapse of granulomatous infectious diseases like tuberculosis.
Why is the use of glucocorticoids in erythema nodosum controversial?
The use of glucocorticoids in erythema nodosum is controversial due to limited evidence supporting their efficacy in this condition.
What is the likely mechanism for steroid-induced hyperglycemia?
Steroid-induced hyperglycemia occurs due to increased gluconeogenesis and insulin resistance caused by glucocorticoids.
What is the likely mechanism for steroid-induced immunosuppression leading to infection?
Glucocorticoids suppress monocyte and lymphocyte function, reducing the immune response and increasing susceptibility to infections.
What is the major naturally occurring glucocorticoid?
Cortisol (hydrocortisone), synthesized from cholesterol by the adrenal cortex.
What percentage of circulating cortisol is unbound and active?
Less than 5%.
What is the average daily cortisol production?
5 to 7 mg/m2, with a diurnal peak around 8:00 am.
How do glucocorticoids affect macrophage functions?
They decrease macrophage functions, including phagocytosis, antigen processing, and cell killing.
What routes can systemic glucocorticoids be administered?
Intralesionally, orally, intramuscularly, and intravenously.
What is a consideration when using glucocorticoids on the face?
Lower concentrations are used to prevent atrophy of the skin.
What are the two primary situations in which intravenous glucocorticoids are used?
- To provide stress coverage for patients who are acutely ill or undergoing surgery and have adrenal suppression from daily glucocorticoid use.
- For patients with certain diseases such as resistant pyoderma gangrenosum, severe pemphigus, or serious systemic lupus erythematosus, to gain rapid control of the disease and minimize the need for long-term, high-dose oral steroid therapy.
What are the fundamental principles to consider before initiating therapy with glucocorticoids?
- Weigh the expected benefits against potential side effects.
- Consider alternative or adjunctive therapies, especially for long-term treatment.
- Take into account coexisting illnesses such as diabetes, hypertension, and osteoporosis.
- Assess the patient’s predisposition to side effects as part of the risk evaluation.
What dietary recommendations should be followed for patients on glucocorticoids?
- Diet should be low in calories, fat, and sodium, and high in protein, potassium, and calcium as tolerated.
- Minimize the use of alcohol, coffee, and nicotine.
- Encourage exercise to help manage side effects.
What precautions should be taken regarding infections for patients on glucocorticoids?
- Patients receiving glucocorticoid doses of 15 mg or greater for 1 month or longer should be screened for tuberculosis with a tuberculin skin test.
- Pay special attention to patients on high doses with underlying lung disease or low lymphocyte counts, as they are at increased risk for infections such as Pneumocystis pneumonia.
What considerations should be made when choosing among glucocorticoids?
- Select a preparation with minimal mineralocorticoid effect to decrease sodium retention.
- Prefer long-term use of prednisone or similar drugs with intermediate half-life and weak steroid-receptor affinity to reduce side effects.
- If a patient does not respond to cortisone or prednisone, consider substituting with cortisol or prednisolone.
What is the recommended limit for the total monthly dose of Kenalog to avoid HPA axis suppression?
20 mg.
What serious side effects are associated with intravenous administration of glucocorticoids?
Anaphylactic reactions, seizures, arrhythmias, and sudden death.
What should be monitored before and after pulse therapy with glucocorticoids?
Serum electrolytes.
What is the importance of considering coexisting illnesses before starting glucocorticoid therapy?
To assess the risk of side effects and tailor treatment accordingly.
What should be included in the baseline evaluation before starting glucocorticoid therapy?
A personal and family history with attention to predisposition to diabetes, hypertension, hyperlipidemia, glaucoma, and associated diseases.
What is the role of protein intake in the diet of patients on glucocorticoids?
To reduce steroid-induced nitrogen wasting.
What is the recommendation for immunization with live vaccines for patients on glucocorticoids?
Can be done if glucocorticoid use is less than 2 weeks at any dose or less than 20 mg/day.
What precautions should be taken regarding immunization with live vaccines in patients receiving high doses of glucocorticoids?
Immunization with live vaccines should not be done for at least 1 month after receiving high doses of glucocorticoids (>20 mg/day) for more than 2 weeks.
What is the recommended calcium and vitamin D supplementation for patients on glucocorticoid therapy for 3 months or longer?
Any patient anticipated to be on glucocorticoid therapy for 3 months or longer should receive calcium 1200 mg/day and vitamin D 800 International Units/day through diet and supplements.
What are the symptoms of adrenal insufficiency associated with long-term glucocorticoid therapy?
Symptoms of adrenal insufficiency include lethargy, weakness, nausea, anorexia, fever, orthostatic hypotension, hypoglycemia.
What are the symptoms of adrenal insufficiency associated with long-term glucocorticoid therapy?
Symptoms of adrenal insufficiency include lethargy, weakness, nausea, anorexia, fever, orthostatic hypotension, hypoglycemia, and weight loss.
What is the relationship between glucocorticoid therapy and cardiovascular disease risk?
Increased risk for ischemic heart disease and heart failure is associated with glucocorticoid therapy, particularly in patients with iatrogenic Cushing syndrome, due to mechanisms like hypercortisolism-induced hypertension and structural changes in the heart.
What should be done if a patient on glucocorticoids develops gastrointestinal complications?
If gastrointestinal complications develop, prophylaxis with a proton pump inhibitor should be initiated, especially in patients with 2 or more risk factors for peptic ulcer disease.
What is the significance of tapering glucocorticoids in patients with adrenal suppression?
Patients receiving daily glucocorticoid therapy for longer than 3 to 4 weeks must be assumed to have adrenal suppression, requiring a tapering of glucocorticoids to allow for recovery of the HPA axis.
A patient on long-term glucocorticoid therapy develops osteoporosis. What preventive measures could have been taken?
Patients on long-term glucocorticoid therapy should receive calcium (1200 mg/day) and vitamin D (800 IU/day) supplementation. Vitamin D levels should be checked and repleted before initiating therapy. Patients at high risk for osteoporosis should be evaluated for secondary causes.
A patient undergoing surgery has been on daily glucocorticoid therapy for 6 weeks. What perioperative management is required?
Patients on daily glucocorticoid therapy for longer than 3-4 weeks are assumed to have adrenal suppression. They should be maintained on their regular glucocorticoid dose, and clinicians should monitor for intraoperative hypotension or adrenal insufficiency.
A patient on glucocorticoids develops peptic ulcers. What could have been done to prevent this?
Patients on glucocorticoids and NSAIDs should receive prophylaxis with a proton pump inhibitor. Prophylaxis is especially important for patients with risk factors like a history of peptic ulcers.
A patient on glucocorticoids for 2 weeks is scheduled for a live vaccine. What should be done?
Live vaccines can be administered if glucocorticoid use is less than 2 weeks at any dose or if the dose is less than 20 mg/day.
A patient develops adrenal insufficiency after stopping glucocorticoids abruptly. What tapering strategy should have been used?
Glucocorticoids should be tapered gradually to allow recovery of the HPA axis. A slower taper or temporarily increasing the dose can help manage symptoms of adrenal insufficiency.
A patient with steroid withdrawal syndrome experiences lethargy and nausea. What is the cause?
Steroid withdrawal syndrome occurs when patients experience symptoms of adrenal insufficiency despite a normal cortisol response. It is due to the body’s adjustment to high glucocorticoid levels.
A patient with steroid-induced hypertension is managed for cardiovascular risk. What should be monitored?
Blood pressure, diet, serum lipids, and glucose levels should be monitored serially. Abnormalities should be treated according to current guidelines.
A patient with steroid-induced osteoporosis is evaluated. What secondary causes should be considered?
Secondary causes like sarcoidosis or renal stones should be evaluated in patients with steroid-induced osteoporosis.
A patient with steroid-induced cataracts is evaluated. What is the likely cause?
Cataracts can develop even with alternate-day dosing of glucocorticoids, likely due to prolonged exposure to the drug.
A patient with steroid-induced adrenal suppression is undergoing surgery. What precautions should be taken?
Patients with adrenal suppression should be maintained on their regular glucocorticoid dose, and clinicians should monitor for signs of adrenal insufficiency during surgery.
A patient with steroid-induced gastrointestinal bleeding is evaluated. What prophylactic measures could have been taken?
Prophylaxis with a proton pump inhibitor should be initiated in patients on glucocorticoids and NSAIDs, especially those with risk factors for GI bleeding.
A patient with steroid-induced avascular necrosis is evaluated. What imaging is recommended?
MRI is recommended for early detection of avascular necrosis, especially if radiographs are normal but suspicion is high.
A patient with steroid-induced HPA axis suppression is evaluated. What is the mechanism?
HPA axis suppression occurs due to the body’s adjustment to exogenous glucocorticoids, leading to reduced endogenous cortisol production.
A patient with steroid-induced hypertension is evaluated. What structural changes may occur?
Structural changes like ventricular hypertrophy and myocardial fibrosis may occur in steroid-induced hypertension.
A patient with steroid-induced osteoporosis is managed. What is the mechanism of bone loss?
Bone loss occurs due to decreased osteoblast activity, increased osteoclast activity, and reduced calcium absorption caused by glucocorticoids.
What should be avoided for at least 1 month after receiving high doses of glucocorticoids?
Immunization with live vaccines.
What is the recommended action for patients receiving glucocorticoid therapy for longer than 3 to 4 weeks?
They must be assumed to have adrenal suppression that requires tapering of the glucocorticoids.
What percentage of individuals treated long-term with systemic glucocorticoids develop osteoporosis?
40%.
What is a significant risk associated with glucocorticoid therapy and nonsteroidal anti-inflammatory agents?
Increased risk for peptic ulcer disease and GI bleeding.
What should patients on glucocorticoid therapy for 3 months or longer receive?
Calcium 1200 mg/day and vitamin D 800 International Units/day.
What is a common symptom of adrenal insufficiency due to glucocorticoid therapy?
Lethargy, weakness, nausea, anorexia, fever, orthostatic hypotension, hypoglycemia, and weight loss.
