Glucocorticoids

Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. These medications are also used for conditions requiring physiologic glucocorticoid replacement. Despite their extensive use, glucocorticoids can produce many and varied adverse effects and should be used judiciously. Because of their immunosuppressive effect, these medications may predispose individuals to infection and should be avoided in those with uncontrolled infections. In addition, long-term therapy can lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis, so discontinuation of therapy should be done carefully to avoid adrenal insufficiency Adrenal Insufficiency Adrenal insufficiency (AI) is the inadequate production of adrenocortical hormones: glucocorticoids, mineralocorticoids, and adrenal androgens. Primary AI, also called Addison’s disease, is caused by autoimmune disease, infections, and malignancy, among others. Adrenal insufficiency can also occur because of decreased production of adrenocorticotropic hormone (ACTH) from disease in the pituitary gland (secondary) or hypothalamic disorders and prolonged glucocorticoid therapy (tertiary). Adrenal Insufficiency and Addison’s Disease.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

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Chemistry and Pharmacodynamics

Chemical structure

  • Glucocorticoids are synthetic analogs of cortisol and cortisone.
  • Alterations may include:
    • Fluorination (dexamethasone, betamethasone)
    • Methylation (methylprednisolone)

Physiology

  • Endogenous glucocorticoids are secreted from the zona fasciculata.
  • Effects: respond to immediate stressors
    • ↑ Immediate available energy through: 
      • Fat and protein catabolism → ↑ blood amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids and lipid levels
      • Gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis
      • Appetite stimulation
    • ↑ RBCs
    • ↑ Serum calcium from bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones resorption (leads to ↓ bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones mineral density over time)
    • Antiinflammatory effects:
      • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
      • ↓ Blood vessel permeability
      • Long-term exposure suppresses the immune system
  • Regulated by the hypothalamic-pituitary-adrenal (HPA) axis
Hypothalamic-pituitary-adrenal cortex axis flowchart

Flowchart showing the hypothalamic-pituitary-adrenal cortex axis:
Stresses may be physical (e.g., exercise), mental (e.g., fear), or biochemical (e.g., low blood glucose). Biologic rhythms include circadian rhythms as well as longer rhythms associated with growth and development.
ACTH: adrenocorticotropic hormone
CRH: corticotropin-releasing hormone

Image by Lecturio.

Mechanism of action

  • Glucocorticoids enter cell → bind to glucocorticoid receptors 
  • Translocation to the nucleus → bind to specific DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure sequences (glucocorticoid response elements) → result in either:
    • Activation of transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription
    • Repression of transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription
  • Results in metabolic effects (similar to normal physiology)
  • Specific genomic immune system effects include:
    • Blocking promotor sites for proinflammatory genes
    • Promoting transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription of antiinflammatory gene products
    • Diminish synthesis of inflammatory cytokines
  • Additional effects:
    • ↓ Inflammatory cytokine secretion
    • ↑ ACE synthesis → bradykinin degradation
      • ↓ Capillary permeability
      • ↓ Vasodilation
    • ↓ Synthesis of phospholipase A2 and COX-2 → ↓ prostaglandin and leukotriene synthesis
    • ↓ Migration of PMNs 
    • ↓ Histamine release

Classification

By use

  • Systemic (see below) 
  • Topical:
    • Betamethasone
    • Clobetasol
    • Fluocinomide
    • Fluticasone
    • Hydrocortisone
    • Mometasone
    • Triamcinolone
  • Inhaled:
    • Beclomethasone 
    • Budesonide
    • Fluticasone 
    • Mometasone

By duration of action

Systemic glucocorticoids can be divided into:

  • Short-acting:
    • Cortisone
    • Hydrocortisone
  • Intermediate-acting:
    • Methylprednisolone
    • Prednisolone
    • Prednisone
    • Triamcinolone
  • Long-acting:
    • Betamethasone
    • Dexamethasone

By potency

Topical steroids are classified as classes I–VII based on their potency.

  • Class I: most potent; includes:
    • Clobetasol propionate
    • Betamethasone dipropionate
    • Diflorasone diacetate
    • Fluocinonide 
  • Class VII: least potent; includes hydrocortisone

Pharmacokinetics

The following summarizes the pharmacokinetics for systemic glucocorticoids:

Absorption

  • Oral absorption is:
    • Rapid
    • Complete
  • Formulations/routes of administration:
    • Oral
    • IV
    • IM
    • Intraarticular

Distribution

  • Protein binding:
    • Natural glucocorticoids are highly protein-bound:
      • Corticosteroid-binding globulin (CBG)
      • Albumin
    • Synthetic steroids are generally less protein-bound.
  • Cross the blood–brain barrier

Metabolism and excretion

  • Metabolism:
    • Hepatic
    • Some by CYP3A4
  • Excretion: primarily in urine

Indications

Systemic

Systemic glucocorticoids are commonly used for the short- and/or long-term management of a variety of conditions, including:

  • Physiologic glucocorticoid replacement
  • Inflammatory diseases
  • Allergic conditions
  • Autoimmune diseases
Table: Common indications for glucocorticoids (list is not exhaustive)
System Indications
Allergic conditions
  • Anaphylaxis
  • Drug hypersensitivity reactions
  • Seasonal allergic rhinitis Rhinitis Rhinitis refers to inflammation of the nasal mucosa. The condition is classified into allergic, nonallergic, and infectious rhinitis. Allergic rhinitis is due to a type I hypersensitivity reaction. Non-allergic rhinitis is due to increased blood flow to the nasal mucosa. Infectious rhinitis is caused by an upper respiratory tract infection. Rhinitis
  • Serum sickness
  • Transfusion reactions Transfusion reactions Transfusion-related complications occur during or after a blood product is given. These complications can be classified as immunologic, non-immunologic and acute, and delayed. Non-immunologic reactions are caused by the transmission of disease in blood products, and immunologic reactions are antigen-antibody-mediated. Transfusion Reactions
Dermatologic
  • Atopic dermatitis Atopic Dermatitis Atopic dermatitis, also known as eczema, is a chronic, relapsing, pruritic, inflammatory skin disease that occurs more frequently in children, although adults can also be affected. The condition is often associated with elevated serum levels of IgE and a personal or family history of atopy. Skin dryness, erythema, oozing, crusting, and lichenification are present. Atopic Dermatitis (Eczema)
  • Contact dermatitis
  • Exfoliative dermatitis and erythroderma
  • Pemphigus vulgaris Pemphigus vulgaris Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In pemphigus vulgaris, autoantibodies attack the desmosomal proteins, which connect the keratinocytes to one another. This attack results in a more severe, potentially fatal condition with fragile, flaccid blisters, usually with significant mucosal involvement. Bullous Pemphigoid and Pemphigus Vulgaris
  • Stevens-Johnson syndrome Stevens-Johnson syndrome Stevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome
  • Severe psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis
Endocrine
  • Congenital adrenal hyperplasia Congenital adrenal hyperplasia Congenital adrenal hyperplasia (CAH) consists of a group of autosomal recessive disorders that cause a deficiency of an enzyme needed in cortisol, aldosterone, and androgen synthesis. The most common subform of CAH is 21-hydroxylase deficiency, followed by 11β-hydroxylase deficiency. Congenital Adrenal Hyperplasia
  • Hypercalcemia Hypercalcemia Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia associated with malignancy
  • Nonsuppurative thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis
  • Primary/secondary adrenocortical insufficiency
  • Septic shock Septic shock Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Septic shock is diagnosed during treatment when vasopressors are necessary to control hypotension. Sepsis and Septic Shock unresponsive to IV fluid resuscitation
GI
  • Inflammatory bowel disease
  • Symptomatic therapy for nausea/vomiting
Hematologic
  • Autoimmune hemolytic anemia Autoimmune Hemolytic Anemia Autoimmune hemolytic anemia (AIHA) is a rare type of hemolytic anemia characterized by antibody production against self RBCs, leading to destruction of these cells in the spleen and other reticuloendothelial tissues. The disease is generally categorized as warm or cold, depending on the thermal reactivity of the autoantibodies. Autoimmune Hemolytic Anemia
  • Congenital (erythroid) hypoplastic anemia
  • Immune thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
  • Lymphomas and leukemias
Neurologic
  • Cerebral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis
Ophthalmic
  • Allergic conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis
  • Allergic corneal marginal ulcers
  • Chorioretinitis Chorioretinitis Chorioretinitis is the inflammation of the posterior segment of the eye, including the choroid and the retina. The condition is usually caused by infections, the most common of which is toxoplasmosis. Some of these infections can affect the fetus in utero and present as congenital abnormalities. Chorioretinitis
  • Diffuse posterior uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea
  • Herpes zoster Herpes Zoster Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Shingles (also known as herpes zoster) is more common in adults and occurs due to the reactivation of VZV. Varicella-Zoster Virus/Chickenpox ophthalmicus
  • Iritis and iridocyclitis
  • Keratitis
  • Optic neuritis
  • Sympathetic ophthalmia
Respiratory
  • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
  • Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)
  • Interstitial lung disease
  • Symptomatic sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
Rheumatologic
  • Acute and subacute bursitis
  • Acute gouty arthritis
  • Acute nonspecific tenosynovitis
  • Ankylosing spondylitis Ankylosing spondylitis Ankylosing spondylitis (also known as Bechterew's disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing Spondylitis
  • Psoriatic arthritis
  • Rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis
  • Synovitis of osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis
  • Exacerbation/maintenance of acute rheumatic carditis
  • Dermatomyositis
  • Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus
  • Vasculitis

Topical

Topical glucocorticoids can be used for a number of dermatologic conditions, including (list is not exhaustive):

  • Psoriasis 
  • Atopic dermatitis Atopic Dermatitis Atopic dermatitis, also known as eczema, is a chronic, relapsing, pruritic, inflammatory skin disease that occurs more frequently in children, although adults can also be affected. The condition is often associated with elevated serum levels of IgE and a personal or family history of atopy. Skin dryness, erythema, oozing, crusting, and lichenification are present. Atopic Dermatitis (Eczema) 
  • Acute radiation dermatitis
  • Lichen planus Lichen planus Lichen planus (LP) is an idiopathic, cell-mediated inflammatory skin disease. It is characterized by pruritic, flat-topped, papular, purple skin lesions commonly found on the flexural surfaces of the extremities. Other areas affected include genitalia, nails, scalp, and mucous membranes. Lichen Planus
  • Discoid lupus erythematosus 
  • Vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo

Inhaled

  • Persistent asthma (prevent exacerbations)
  • Stable chronic obstructive pulmonary disease (prevent exacerbations)
  • Eosinophilic esophagitis Esophagitis Esophagitis is the inflammation or irritation of the esophagus. The major types of esophagitis are medication-induced, infectious, eosinophilic, corrosive, and acid reflux. Patients typically present with odynophagia, dysphagia, and retrosternal chest pain. Esophagitis (not inhaled, but swallowed)

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Adverse Effects and Contraindications

Adverse effects

  • Endocrine:
    • Cushingoid features
    • Cushing syndrome
    • Hyperglycemia and diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
    • Growth suppression in children and adolescents
    • Weight gain
  • Immunologic/infectious:
    • Thrush
    • Immunosuppression → invasive infections
  • Hematologic: neutrophilia from demargination
  • GI:
    • Ulcers
    • Gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis
  • Neurologic:
    • Psychosis
    • Insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia
    • Irritability
    • Anxiety
    • Mood lability
    • ↑ Appetite
  • Ophthalmologic: 
    • Glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma
    • Cataracts
  • Musculoskeletal:
    • Myopathy: 
      • Proximal muscle weakness
      • Myalgias
    • Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
    • Osteonecrosis
  • Dermatologic:
    • Skin atrophy
    • Striae
    • Purpura
    • Impaired wound healing Wound healing Wound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling. Wound Healing
    • Hypertrichosis
  • Withdrawal:
    • Long-term therapy results in HPA-axis suppression
    • Abrupt discontinuation may cause adrenal insufficiency Adrenal Insufficiency Adrenal insufficiency (AI) is the inadequate production of adrenocortical hormones: glucocorticoids, mineralocorticoids, and adrenal androgens. Primary AI, also called Addison’s disease, is caused by autoimmune disease, infections, and malignancy, among others. Adrenal insufficiency can also occur because of decreased production of adrenocorticotropic hormone (ACTH) from disease in the pituitary gland (secondary) or hypothalamic disorders and prolonged glucocorticoid therapy (tertiary). Adrenal Insufficiency and Addison’s Disease

Contraindications and precautions

  • Contraindications:
    • Recent administration of live or live attenuated vaccines
    • Systemic fungal infections
    • Other uncontrolled active infections
  • Use with caution with:
    • Psychosis
    • Uncontrolled hyperglycemia
    • Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
    • Diverticulitis or recent intestinal anastomoses → risk of perforation
    • Severe hepatic or renal impairment
    • Recent acute MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction → risk of wall rupture

Drug interactions

  • ↑ Risk of ulcers and GI bleeding: NSAIDs
  • ↓ Absorption of glucocorticoids:
    • Proton pump inhibitors
    • Antacids
    • Bile acid sequestrants
  • ↑ Metabolism of glucocorticoids due to induction of CYP3A4:
    • Phenobarbital
    • Phenytoin
    • Rifampin
  • ↓ Metabolism of glucocorticoids due to inhibition of CYP3A4:
    • Ritonavir
    • Clarithromycin
    • Voriconazole
  • Dosing adjustment may be necessary for antidiabetic agents.

References

  1. Gabros, S., Nessel, T.A., Zeto, P.M. (2020). Topical corticosteroids. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK532940/
  2. Yasir, M., et al. (2021). Corticosteroid adverse effects. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK531462/
  3. Corticosteroids: drug information. UpToDate, retrieved from https://www.uptodate.com/contents/table-of-contents/drug-information/general-drug-information
  4. Nieman, L.K. (2021). Pharmacologic use of glucocorticoids. UpToDate. Retrieved November 7, 2021, from https://www.uptodate.com/contents/pharmacologic-use-of-glucocorticoids
  5. Saag, K.G., Furst, D.E. (2021). Major side effects of systemic glucocorticoids. UpToDate. Retrieved November 7, 2021, from https://www.uptodate.com/contents/major-side-effects-of-systemic-glucocorticoids
  6. Chatham, W.W. (2021). Glucocorticoid effects on the immune system. UpToDate. Retrieved November 7, 2021, from https://www.uptodate.com/contents/glucocorticoid-effects-on-the-immune-system
  7. Hodgens, A., Sharma, T. (2021). Corticosteroids. StatPearls. Retrieved November 7, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK554612/
  8. Gabros, S., Nessel, T.A., Zito, P.M. (2021). Topical corticosteroids. StatPearls. Retrieved November 7, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK532940/
  9. Liang, T.Z., Chao, J.H. (2021). Inhaled corticosteroids. StatPearls. Retrieved November 7, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK470556/
  10. Chrousos, G.P. (2012). Adrenocorticosteroids & adrenocortical antagonists. In: Katzung, B.G., Masters, S.B., Trevor, A.J. (Eds.), Basic & Clinical Pharmacology, 12th ed. McGraw-Hill, pp. 697–713). https://pharmacomedicale.org/images/cnpm/CNPM_2016/katzung-pharmacology.pdf

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