Pharmacology of Corticosteroids

Introduction/Overview

Corticosteroids represent a cornerstone class of therapeutic agents with profound and diverse physiological effects. These synthetic analogues of endogenous adrenal cortex hormones are among the most widely prescribed drugs globally due to their potent anti-inflammatory and immunosuppressive properties. The clinical utility of corticosteroids spans nearly every medical specialty, from rheumatology and pulmonology to dermatology, hematology, and oncology. Their introduction into clinical practice in the mid-20th century revolutionized the management of numerous inflammatory and autoimmune conditions, though their potent efficacy is counterbalanced by a significant and often dose-limiting profile of adverse effects. A thorough understanding of their pharmacology is therefore essential for safe and effective clinical application.

The clinical relevance of corticosteroids cannot be overstated. They serve as first-line therapy for conditions such as asthma exacerbations, systemic lupus erythematosus, and acute transplant rejection, and as critical adjuncts in the management of septic shock and certain malignancies. Their importance is further underscored by their role in replacement therapy for adrenal insufficiency, a potentially life-saving intervention. Mastery of corticosteroid pharmacology involves not only knowing when and how to initiate therapy but, perhaps more critically, understanding the strategies for dose minimization, tapering, and monitoring to mitigate long-term toxicity.

Learning Objectives

• Classify corticosteroids based on their relative glucocorticoid and mineralocorticoid activity and their duration of action.
• Explain the genomic and non-genomic molecular mechanisms underlying the anti-inflammatory, immunosuppressive, and metabolic effects of corticosteroids.
• Compare and contrast the pharmacokinetic properties, including absorption, distribution, metabolism, and elimination, of major systemic and topical corticosteroids.
• Identify the major therapeutic indications for corticosteroids across organ systems and describe the principles of dosing and administration for specific conditions.
• Analyze the spectrum of adverse effects associated with corticosteroid use, categorizing them by system and relating them to dose and duration of therapy, and develop monitoring strategies to detect and manage these effects.

Classification

Corticosteroids are systematically classified according to their origin, chemical structure, biological activity, and duration of action. The primary categorization is based on their predominant physiological effect, which mirrors the functions of the two major zones of the adrenal cortex: the zona glomerulosa and the zona fasciculata.

Classification by Biological Activity

The two principal classes are glucocorticoids and mineralocorticoids. Glucocorticoids, such as cortisol (hydrocortisone), primarily influence carbohydrate, protein, and fat metabolism and possess potent anti-inflammatory and immunosuppressive actions. Mineralocorticoids, such as aldosterone, mainly regulate electrolyte and water balance by promoting sodium reabsorption and potassium excretion in the distal renal tubules. Most synthetic agents are designed to maximize glucocorticoid effects while minimizing undesirable mineralocorticoid activity, though the degree of separation varies.

Chemical Classification and Structural Modifications

All corticosteroids share a cyclopentanoperhydrophenanthrene (steroid) nucleus. Strategic chemical modifications to the cortisol structure have yielded compounds with enhanced potency, altered receptor affinity, and modified pharmacokinetic profiles. Key modifications include:

• Introduction of a double bond between C1 and C2 (as in prednisone and prednisolone): This increases glucocorticoid potency approximately four-fold.
• Addition of a fluorine atom at C9 (as in triamcinolone, dexamethasone, and betamethasone): This dramatically increases both glucocorticoid and mineralocorticoid receptor affinity, though subsequent modifications can mitigate the mineralocorticoid effect.
• Addition of a methyl group at C16 (as in dexamethasone and betamethasone): This virtually eliminates mineralocorticoid activity while further enhancing glucocorticoid potency.
• Addition of a hydroxyl or methyl group at C16 (as in triamcinolone): This also reduces mineralocorticoid activity.

Classification by Duration of Action

This practical classification, based on the biological half-life of the hypothalamic-pituitary-adrenal (HPA) axis suppression, guides dosing frequency and clinical use.

• Short-acting (8–12 hours): Hydrocortisone, cortisone. These have significant mineralocorticoid activity and are often used for physiological replacement.
• Intermediate-acting (18–36 hours): Prednisone, prednisolone, methylprednisolone, triamcinolone. This group forms the mainstay of therapeutic anti-inflammatory and immunosuppressive regimens.
• Long-acting (36–54 hours): Dexamethasone, betamethasone. These are used when minimal mineralocorticoid effect and prolonged action are desired, such as in cerebral edema or antiemetic protocols.

Classification by Route of Administration

Corticosteroids are formulated for diverse routes to maximize local effect and minimize systemic exposure. These include oral, intravenous, intramuscular, intra-articular, inhalational, intranasal, topical (dermatological), ophthalmic, and rectal preparations. The potency of topical and inhalational agents is often described on a standardized scale relative to hydrocortisone.

Mechanism of Action

The pharmacological effects of corticosteroids are mediated through complex and multifaceted mechanisms, broadly divisible into genomic (slow, transcriptional) and non-genomic (rapid, non-transcriptional) pathways. The genomic effects are responsible for most of the therapeutic and chronic adverse effects.

Genomic Mechanisms: Cytosolic Glucocorticoid Receptor Activation

This is the primary and most well-characterized mechanism. Glucocorticoids are lipophilic and passively diffuse across the cell membrane. In the cytoplasm, they bind to the ubiquitously expressed glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. In its inactive state, the GR is complexed with chaperone proteins, including heat shock protein 90 (Hsp90). Ligand binding induces a conformational change, causing dissociation of the chaperone proteins, receptor dimerization, and rapid translocation of the activated GR complex into the nucleus.

Within the nucleus, the GR complex modulates gene transcription through two principal mechanisms:

1. Transactivation: The GR dimer binds to specific DNA sequences known as glucocorticoid response elements (GREs) in the promoter regions of target genes. This binding recruits co-activator proteins and the transcriptional machinery, leading to increased mRNA synthesis and subsequent protein production. Transactivation is generally associated with certain metabolic side effects (e.g., induction of gluconeogenic enzymes like phosphoenolpyruvate carboxykinase) and some anti-inflammatory proteins like annexin-1 (lipocortin-1).
2. Transrepression: This mechanism is considered more critical for the anti-inflammatory and immunosuppressive effects. The activated GR monomer can interact with and inhibit the activity of key pro-inflammatory transcription factors, primarily nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), by direct protein-protein binding. This interaction prevents these factors from binding to their response elements on DNA, thereby repressing the transcription of a vast array of inflammatory mediators, including cytokines (e.g., IL-1, IL-2, IL-6, TNF-α), chemokines, adhesion molecules, and inflammatory enzymes like cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS).

Non-Genomic Mechanisms

These effects occur within seconds to minutes, too rapidly to be explained by gene transcription and protein synthesis. Proposed mechanisms include:

• Interaction with membrane-associated receptors: Some effects may be mediated by specific membrane-bound GR variants or related receptors.
• Non-specific physicochemical interactions: At very high (pharmacological) concentrations, corticosteroids can intercalate into cellular membranes, altering ion channel function and membrane fluidity, which may contribute to rapid effects seen in emergency settings like anaphylaxis.
• Modulation of secondary messenger systems: Rapid inhibition of calcium and potassium ion fluxes and modulation of arachidonic acid release have been observed.

Cellular and Physiological Effects

The molecular mechanisms translate into broad cellular and systemic effects:

• Anti-inflammatory: Suppression of leukocyte recruitment and function (margination, diapedesis, chemotaxis), inhibition of phagocytosis and lysosomal enzyme release, and stabilization of lysosomal and other intracellular membranes.
• Immunosuppressive: Inhibition of T-lymphocyte and B-lymphocyte proliferation and function, reduction in antibody production, and induction of apoptosis in certain lymphocyte subsets.
• Metabolic: Stimulation of gluconeogenesis, antagonism of insulin action (peripheral glucose uptake), promotion of lipolysis and redistribution of adipose tissue, and stimulation of protein catabolism.
• Cardiovascular/Renal: Mineralocorticoid effects (Na⁺ retention, K⁺ and H⁺ excretion) increase blood volume and pressure. Glucocorticoids also enhance vascular sensitivity to catecholamines (permissive effect).
• Other: Effects on bone (inhibition of osteoblast function, stimulation of osteoclast activity), skin (atrophy), CNS (mood alterations), and fibroblasts (inhibition of collagen synthesis).

Pharmacokinetics

The pharmacokinetic properties of corticosteroids vary significantly between agents and are heavily influenced by chemical structure, formulation, and route of administration. Understanding these parameters is crucial for selecting the appropriate drug, dose, and regimen.

Absorption

Most oral corticosteroids (e.g., prednisone, dexamethasone) are well absorbed from the gastrointestinal tract, with bioavailability typically exceeding 70-90%. The presence of food may delay but does not significantly reduce overall absorption. For parenteral administration, water-soluble esters (e.g., sodium succinate, sodium phosphate) are used for intravenous or intramuscular injection, providing rapid onset. Repository or depot formulations (e.g., methylprednisolone acetate, triamcinolone acetonide) are less soluble esters designed for intramuscular or intra-articular injection, resulting in slow absorption and prolonged local or systemic effects lasting weeks. Topical and inhalational absorption is generally low but can become clinically significant with high-potency agents, large surface area application, occlusive dressings, or impaired skin barrier.

Distribution

Corticosteroids are widely distributed throughout body tissues. They are highly protein-bound in plasma, primarily to corticosteroid-binding globulin (transcortin) and, to a lesser extent, albumin. The free, unbound fraction is the pharmacologically active moiety. Synthetic corticosteroids like dexamethasone have lower affinity for transcortin and a higher free fraction. The volume of distribution is moderate, approximating total body water. Corticosteroids readily cross the placenta and appear in breast milk.

Metabolism

Hepatic metabolism is the primary route of biotransformation. The key metabolic pathways include:

• Reduction: The 4,5 double bond and the 3-keto group are reduced by hepatic enzymes (e.g., 5α- and 5β-reductases).
• Hydroxylation: Various cytochrome P450 (CYP) enzymes, particularly CYP3A4, catalyze hydroxylation reactions.
• Conjugation: The resulting metabolites are conjugated with glucuronic acid or sulfate to form water-soluble, inactive compounds ready for excretion.

A critical activation step occurs with prodrugs. Prednisone is an inactive prodrug that must be reduced to prednisolone by hepatic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to exert its effect. This conversion may be impaired in patients with severe liver disease, making prednisolone the preferred agent in such cases.

Excretion

Renal excretion of the conjugated metabolites is the principal route of elimination. Less than 1% of an administered dose is excreted unchanged in the urine. The elimination half-life (t_1/2) in plasma varies considerably and forms the basis for the duration-of-action classification: short-acting (1–2 hours), intermediate-acting (2–5 hours), and long-acting (4–6 hours). It is crucial to distinguish this plasma half-life from the much longer biological half-life (duration of HPA axis suppression), which is determined by the persistence of the drug-receptor complex and its downstream genomic effects.

Dosing Considerations

Dosing is highly individualized based on the disease, severity, treatment goal (induction vs. maintenance), and patient factors. General principles include:

• Using the lowest effective dose for the shortest possible duration.
• Administering intermediate-acting agents in a single morning dose to mimic the physiological diurnal cortisol rhythm and minimize HPA axis suppression.
• Considering alternate-day therapy with intermediate-acting agents for certain chronic conditions to reduce adverse effects while maintaining efficacy.
• Employing “pulse” therapy (very high intravenous doses for a few days) for severe, acute autoimmune flares.
• Always implementing a gradual taper when discontinuing systemic therapy after more than 2-3 weeks of use to avoid adrenal insufficiency and disease flare.

Therapeutic Uses/Clinical Applications

The therapeutic applications of corticosteroids are extensive, reflecting their broad suppressive effects on inflammation and immunity. Their use can be categorized as replacement therapy or pharmacotherapy.

Replacement Therapy

Physiological doses are used to correct hormone deficiency.

• Primary adrenal insufficiency (Addison’s disease): Requires combined glucocorticoid (e.g., hydrocortisone 15-25 mg daily in divided doses) and mineralocorticoid (fludrocortisone) replacement.
• Secondary/tertiary adrenal insufficiency: Due to pituitary or hypothalamic disease, requiring glucocorticoid replacement only.
• Congenital adrenal hyperplasia: Glucocorticoids suppress ACTH overdrive and androgen overproduction.

Pharmacotherapeutic Uses (Supraphysiological Doses)

Rheumatology and Autoimmune Diseases: First-line or cornerstone therapy for systemic lupus erythematosus, rheumatoid arthritis (especially during flares), polymyalgia rheumatica, giant cell arteritis, vasculitides (e.g., granulomatosis with polyangiitis), and inflammatory myopathies.

Pulmonary Diseases:

• Asthma: Inhaled corticosteroids are mainstay controller therapy. Systemic corticosteroids are critical for managing moderate-to-severe exacerbations.
• Chronic Obstructive Pulmonary Disease (COPD): Systemic steroids for acute exacerbations.
• Interstitial Lung Diseases: Used in sarcoidosis, idiopathic pulmonary fibrosis (acute exacerbations), and hypersensitivity pneumonitis.
• Prevention of Neonatal Respiratory Distress Syndrome: Administered antenatally to mothers at risk of preterm delivery to accelerate fetal lung maturation (betamethasone or dexamethasone).

Dermatology: Topical corticosteroids are first-line for a wide range of inflammatory skin disorders (eczema, psoriasis, lichen planus). Systemic steroids are used for severe conditions like pemphigus vulgaris, toxic epidermal necrolysis, and severe erythema multiforme.

Gastroenterology: For induction of remission in inflammatory bowel disease (Crohn’s disease, ulcerative colitis), and autoimmune hepatitis.

Hematology/Oncology:

• Component of chemotherapy regimens for lymphomas (e.g., CHOP for non-Hodgkin lymphoma) and leukemias (e.g., ALL).
• Management of complications: Hypercalcemia of malignancy, appetite stimulation in cancer cachexia, prevention of chemotherapy-induced nausea/vomiting (dexamethasone), and management of spinal cord compression from metastatic disease.
• Treatment of autoimmune hemolytic anemia and immune thrombocytopenic purpura.

Neurology: For acute exacerbations of multiple sclerosis, cerebral edema associated with primary or metastatic brain tumors, and bacterial meningitis (adjunctive therapy with dexamethasone).

Infectious Diseases: Adjunctive therapy in specific severe infections to modulate detrimental host inflammatory responses: Pneumocystis jirovecii pneumonia with hypoxemia, severe typhoid fever, and tuberculous meningitis.

Transplantation: A key component of immunosuppressive regimens to prevent and treat acute allograft rejection.

Other: Allergic reactions (anaphylaxis, severe contact dermatitis), septic shock (controversial, may be considered in specific scenarios with ongoing vasopressor requirement), and intra-articular injections for osteoarthritis or inflammatory arthritis.

Adverse Effects

The adverse effect profile of corticosteroids is extensive and correlates strongly with the dose, duration of therapy, and specific agent used. Adverse effects can be grouped into those resulting from withdrawal of therapy and those arising from continued administration.

Effects of Withdrawal

• Adrenal Insufficiency (HPA axis suppression): The most serious withdrawal effect. Chronic exogenous glucocorticoid administration suppresses CRH and ACTH secretion, leading to adrenal atrophy. Abrupt cessation can precipitate an adrenal crisis characterized by hypotension, hyponatremia, hyperkalemia, fever, and death. A slow, graded taper is mandatory.
• Steroid withdrawal syndrome: A poorly understood syndrome of malaise, anorexia, nausea, lethargy, headache, fever, and arthralgias that can occur even with a slow taper, possibly due to relative tissue steroid deficiency despite normal cortisol levels.
• Recrudescence of underlying disease.

Effects of Continued Administration

Endocrine/Metabolic:

• Iatrogenic Cushing’s syndrome: Characterized by central obesity, moon facies, dorsal buffalo hump, and supraclavicular fat pads.
• Hyperglycemia and steroid-induced diabetes mellitus due to increased gluconeogenesis and insulin resistance.
• Dyslipidemia (increased triglycerides, altered LDL/HDL profile).
• Suppression of the HPA axis.
• Growth retardation in children.

Musculoskeletal:

• Osteoporosis and increased fracture risk: A major dose-limiting toxicity. Mechanisms include inhibition of osteoblast function, stimulation of osteoclast activity, reduced intestinal calcium absorption, and increased renal calcium excretion.
• Osteonecrosis (avascular necrosis), particularly of the femoral head.
• Myopathy: Proximal muscle weakness, especially with fluorinated steroids.

Cardiovascular: Hypertension (from mineralocorticoid activity and increased vascular reactivity), fluid retention, edema, and accelerated atherosclerosis.

Gastrointestinal: Dyspepsia, peptic ulcer disease (risk is debated but co-therapy with NSAIDs increases risk), pancreatitis, and hepatic steatosis.

Neuropsychiatric: Insomnia, mood disturbances (euphoria, depression, psychosis), cognitive impairment, and increased intracranial pressure with chronic use (pseudotumor cerebri).

Ophthalmic: Posterior subcapsular cataracts, glaucoma (with topical ophthalmic or systemic use).

Dermatological: Skin atrophy, striae, purpura, impaired wound healing, and acne.

Immunological: Increased susceptibility to infections (especially opportunistic infections like candidiasis, pneumocystosis, reactivation of latent tuberculosis or herpes viruses), and potential masking of classic signs of infection (fever, inflammation).

Other: Leukocytosis (demargination of neutrophils), redistribution of body fat, and electrolyte disturbances (hypokalemia, metabolic alkalosis).

Black Box Warnings

Systemic corticosteroids carry a black box warning regarding the risk of serious, potentially fatal infections. Patients on corticosteroids are more susceptible to new infections, may have atypical presentations, and are at risk for reactivation of latent infections. Vaccination with live-attenuated vaccines is generally contraindicated. Additional warnings highlight the potential for adrenal insufficiency upon withdrawal and the multiple serious adverse reactions associated with corticosteroid use across organ systems.

Drug Interactions

Corticosteroids participate in numerous pharmacokinetic and pharmacodynamic drug interactions that can alter their efficacy or toxicity, or the effects of co-administered drugs.

Major Pharmacokinetic Interactions

• Enzyme Inducers: Drugs that induce hepatic CYP3A4 (e.g., phenytoin, phenobarbital, carbamazepine, rifampin, St. John’s wort) can significantly increase the metabolic clearance of corticosteroids (especially prednisolone, methylprednisolone), reducing their therapeutic effect. Dose adjustments may be required.
• Enzyme Inhibitors: Drugs that inhibit CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) can decrease corticosteroid metabolism, potentially increasing both therapeutic and toxic effects.
• Antacids and Bile Acid Sequestrants: May reduce the absorption of orally administered corticosteroids when given concomitantly.

Major Pharmacodynamic Interactions

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Concurrent use significantly increases the risk of gastrointestinal ulceration and bleeding.
• Anticoagulants (Warfarin): Corticosteroids may alter the response to warfarin, variably increasing or decreasing the INR; close monitoring is required.
• Antidiabetic Agents (Insulin, Oral Hypoglycemics): The hyperglycemic effect of corticosteroids antagonizes the action of these drugs, necessitating dose adjustments and frequent glucose monitoring.
• Diuretics (especially potassium-wasting, e.g., thiazides, loop diuretics): Corticosteroids with mineralocorticoid activity can exacerbate hypokalemia.
• Digitalis Glycosides: Hypokalemia induced by corticosteroids can potentiate digitalis toxicity (arrhythmias).
• Vaccines: Immunosuppressive doses of corticosteroids can diminish the antibody response to killed vaccines and increase the risk of disseminated infection with live-attenuated vaccines (e.g., MMR, varicella, yellow fever).
• Neuromuscular Blocking Agents: Chronic corticosteroid use may potentiate or prolong the effects of these agents.

Contraindications

Absolute contraindications to systemic corticosteroid therapy are few but include:

• Systemic fungal infection (unless used for management of adrenal insufficiency in such patients).
• Known hypersensitivity to the specific corticosteroid or formulation excipients.
• Administration of live virus vaccines in immunocompromised individuals.

Relative contraindications, requiring careful risk-benefit assessment, include: active peptic ulcer disease, uncontrolled hypertension, congestive heart failure, diabetes mellitus, osteoporosis, severe psychiatric disorders, active tuberculosis or other untreated latent infections, glaucoma, and herpes simplex keratitis.

Special Considerations

Use in Pregnancy and Lactation

Pregnancy: Corticosteroids cross the placenta, but the degree varies. Hydrocortisone and prednisolone are inactivated by placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), resulting in lower fetal exposure (≈10% of maternal dose). Betamethasone and dexamethasone are poor substrates for this enzyme and readily cross, making them the agents of choice when a direct fetal effect is desired (e.g., lung maturation). Chronic maternal use in the first trimester may be associated with a small increased risk of oral clefts. Use throughout pregnancy has been associated with an increased risk of preterm birth, low birth weight, and possibly neonatal adrenal suppression. Corticosteroids should be used when clearly indicated, at the lowest effective dose, and preferably with agents like prednisone/prednisolone for maternal conditions.

Lactation: Corticosteroids are excreted in breast milk in small quantities. Prednisone at doses ≤ 20 mg daily is generally considered compatible with breastfeeding, as the infant receives less than 10% of the maternal dose. Dosing immediately after breastfeeding and waiting 3-4 hours before the next feed can minimize infant exposure. High-dose therapy may warrant temporary cessation of breastfeeding.

Pediatric Considerations

Children are particularly susceptible to certain corticosteroid toxicities. Growth suppression is a major concern with chronic use, mediated by inhibition of growth hormone secretion and direct effects on epiphyseal cartilage. Monitoring growth velocity is essential. Alternate-day dosing may mitigate this effect. Behavioral changes and increased intracranial pressure (pseudotumor cerebri) are also more common in children. Live virus vaccinations should be deferred. Dosing is typically weight-based (mg/kg), but the principles of using the lowest effective dose and shortest duration remain paramount.

Geriatric Considerations

Older adults are at increased risk for many corticosteroid-induced complications, including hypertension, hyperglycemia, osteoporosis, fractures, cataracts, and infections. Age-related reductions in renal or hepatic function may alter drug clearance. The presence of multiple comorbidities and polypharmacy increases the risk of drug interactions (e.g., with anticoagulants, diuretics, antidiabetic drugs). A lower starting dose and vigilant monitoring for adverse effects are warranted.

Renal and Hepatic Impairment

Renal Impairment: Dose adjustment is generally not required for corticosteroids themselves, as elimination of inactive metabolites may be delayed but is not clinically significant. However, caution is needed regarding fluid retention, hypertension, and electrolyte disturbances (hypokalemia), which may be exacerbated in renal disease. Monitoring of weight, blood pressure, and electrolytes is crucial.

Hepatic Impairment: Severe liver disease can impair the metabolism of corticosteroids. More importantly, the conversion of the prodrug prednisone to active prednisolone by hepatic 11β-HSD1 may be reduced. Therefore, prednisolone is preferred over prednisone in patients with significant hepatic dysfunction. Plasma levels of corticosteroids may be elevated due to reduced clearance and decreased synthesis of binding proteins (albumin, transcortin), potentially increasing the free, active fraction. Dose reduction may be necessary, and patients should be monitored closely for signs of toxicity.

Summary/Key Points

• Corticosteroids are synthetic analogues of adrenal hormones, classified by duration of action (short, intermediate, long) and predominant activity (glucocorticoid vs. mineralocorticoid).
• Their primary mechanism involves binding to cytosolic glucocorticoid receptors, leading to genomic effects (transrepression of pro-inflammatory genes is key for therapeutic effect) and slower non-genomic effects.
• Pharmacokinetics vary: oral absorption is generally excellent; metabolism is hepatic (CYP3A4); excretion is renal as inactive metabolites. The biological effect lasts far longer than the plasma half-life.
• Clinical uses are vast, encompassing replacement therapy for adrenal insufficiency and pharmacotherapy for inflammatory, autoimmune, allergic, neoplastic, and other disorders across all medical specialties.
• The adverse effect profile is extensive and dose/duration-dependent, including metabolic (Cushing’s, diabetes), musculoskeletal (osteoporosis, myopathy), cardiovascular (hypertension), gastrointestinal, neuropsychiatric, ophthalmic (cataracts), dermatological, and immunological (increased infection risk) effects.
• Significant drug interactions occur with enzyme inducers/ inhibitors, NSAIDs, anticoagulants, antidiabetics, diuretics, and vaccines. Abrupt withdrawal can cause adrenal crisis.
• Special populations require careful management: use prednisolone in severe liver disease; monitor growth in children; be vigilant for polypharmacy interactions in the elderly; and prefer prednisone/prednisolone for maternal conditions in pregnancy.

Clinical Pearls

• Always use the lowest effective dose for the shortest possible duration. This is the cardinal rule of corticosteroid therapy.
• For chronic daily therapy, administer intermediate-acting agents (e.g., prednisone) as a single morning dose to minimize HPA axis suppression.
• Never stop systemic corticosteroid therapy abruptly if it has been used for more than 2-3 weeks. A gradual taper is mandatory to assess disease control and prevent adrenal insufficiency.
• Consider prophylaxis for Pneumocystis jirovecii pneumonia (e.g., with trimethoprim-sulfamethoxazole) in patients on prolonged high-dose (≥20 mg prednisone equivalent daily for ≥4 weeks) or combination immunosuppressive therapy.
• Initiate bone protection strategies (calcium, vitamin D supplementation, and often a bisphosphonate) at the start of anticipated long-term (≥3 months) oral corticosteroid therapy at any dose, or in postmenopausal women and men over 50 receiving shorter courses at high dose (≥7.5 mg prednisone equivalent daily).
• When switching from intravenous to oral therapy, remember that oral prednisone is approximately 80% as bioavailable as intravenous methylprednisolone. A common conversion is IV methylprednisolone 40 mg ≈ oral prednisone 50 mg.

References

1. Whalen K, Finkel R, Panavelil TA. Lippincott Illustrated Reviews: Pharmacology. 7th ed. Philadelphia: Wolters Kluwer; 2019.
2. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.
3. Katzung BG, Vanderah TW. Basic & Clinical Pharmacology. 15th ed. New York: McGraw-Hill Education; 2021.
4. Golan DE, Armstrong EJ, Armstrong AW. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 4th ed. Philadelphia: Wolters Kluwer; 2017.
5. Trevor AJ, Katzung BG, Kruidering-Hall M. Katzung & Trevor's Pharmacology: Examination & Board Review. 13th ed. New York: McGraw-Hill Education; 2022.
6. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill Education; 2023.
7. Whalen K, Finkel R, Panavelil TA. Lippincott Illustrated Reviews: Pharmacology. 7th ed. Philadelphia: Wolters Kluwer; 2019.
8. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.