Adrenocorticosteroids (Glucocorticoids and Mineralocorticoids)

Vocabulary-style flashcards covering key terms, pathways, actions, clinical uses, and pharmacologic modifiers of adrenocorticosteroids.

Adrenal cortex

Outer layer of the adrenal gland with three zones (glomerulosa, fasciculata, reticularis) that secrete mineralocorticoids, glucocorticoids, and androgens.

Zona glomerulosa

Adrenal zone that secretes aldosterone; activity regulated by the renin–angiotensin–aldosterone system (RAAS).

Zona fasciculata

Adrenal zone that secretes glucocorticoids (chiefly cortisol) and corticosterone.

Zona reticularis

Adrenal zone that secretes androgens (sex steroids) such as DHEA and androstenedione.

Adrenal medulla

Inner part of the adrenal gland; secretes predominantly epinephrine and norepinephrine.

Glucocorticoids

Cortisol or Hydrocortisone by HPA

Glucocorticoids and aldosterone are essential for life

Glucocorticoid Metabolic Actions

Carb Metabolism - anti-insulin effect, Hyperglycemia

Protein Metabolism - inhibits protein synthesis in muscles, connective tissues, skin

Fat Metabolism - Increase glucocorticoid levels increase fat deposition, centripetal obesity, cutaneous striae

Glucocorticoid Antiinflammatory Actions

Inhibits phosphlipase A2 via lipocortin production and lowers prostaglandins

Blocks synthesis and release of cytokines (IL 1, IL 4, IL 6, TNF)

Suppress fibroblast proliferation and proinflammatory transcription factors

Mast cell and basophils decrease IgE dependent release of histamine and LTC4 respectively

Glucocorticoids Immunosuppressive Actions

Suppress the cell mediated immunity

Suppress humoral immunity

Controls graft rejection by reducing antigen expression, delay revascularization, decrease cytotoxic lymphocytes

Glucocorticoid Other Actions

Ca metabolism - Antagonize vit D3, osteoporosis on long term

Central Nervous System - Euphoria, anxiety, insomnia, depression

Cardiovascular - hypertension, coronary artery disease

Skeletal Muscles - muscle wasting and weakness in cortisol excess

Plays vital role in fetal lung development (pulm surfactant), depress growth hormone secretion, associated w development of peptic ulcers

Aldosterone Effects

Promotes Na reabsorption

Enhance excretion of K and H

Corticosteroid preparations

Corticosteroid preparations

Cinical Uses Endocrinal Replacement Therapy

Acute Adrenal Insufficiency, Chronic Adrenal Insufficiency

Clinical Uses - Endocrine Maintenance Therapy

Cushings Syndrom, Congenital Adrenal Hyperplasia

Dexamethasone suppression test

Clinical Uses Antiinflammatory Therapy

Osteoarthritis, Rheumatic fever, Gout, Rh Arthritis, IBD, Allergic conjunctivitis, iridocyclitis, iritis

Clinical Uses Immunosuppressive Therapy

Collagen Vascular Disease, Organ Transplant/skin graft, Nephrotic syndrome, AI disease (AI hemolytic anemia, Immune thrombocytopenia purpura, myastenia gravis), MS, Guillain Barre Syn.

Clinical Uses NonEdocrinal

Bronchial Asthma - systemic steroid for acute sever, Inhaled for long term (beclomethasone, budesonide, fluticasone, flunisolide)

Severe allergic rxn, stimulation of fetal lung maturation, malignancies, skin disease

Glucocorticoids A/E

Altered fat distiribution, Edema from Na retention, Osteoporosins, Hyperglycemia, susceptible to infections, delayed healing, peptic ulcer, acne, ocular effects, CNS effects, fragile skin, anovulation, gynecomastia, suppression of HPA axis, myopathy, growth retardation, cutaneous atrophy

Glucocorticoids C/I

Diabetes, Osteoporosis, TB and bacteria infection, Herpes Keratitis, Epilepsy, Renal failure, Peptic ulcer, Pregnancy, psychosis, fungal and viral infections, CHF and hypertension

Adrenocorticoids: Pharmacologic Actions

Mineralocorticoid actions - mediated by aldosterone, regulates Na, K and fluid homeostasis

Gluococorticoid actions - mediated by cortisol, governs protein, fat, and carb metabolism, antiinflammatory, immunosuppressant

Principles in Steroid Therapy

Risk of iatrogenic Cushing’s syndrome (most common cause of Cushings), use local therapy, single high dose, less than 1 weeks, short courses

Long term Rx - hazardous due to A/E profile, alternate day dosing to minimize HPA axis suppression, slow tapering, increase dose in stressful events

Ketoconazole

17 alpha hydroxylase inhibitor - antifungal, cushing’s syndrome

Mifepristone

Antagonist at progesterone and glucocorticoid receptors

Mineralocorticoid antagonist

Spironolactone, eplerenone

HPA axis

Hypothalamic-pituitary-adrenal axis; regulates cortisol production via CRH, ACTH, and negative feedback.

Dexamethasone suppression test (DST)

Diagnostic test to determine source of cortisol excess (adrenal vs ectopic/pituitary) by dexamethasone suppression.

Primary adrenal insufficiency (Addison’s disease)

Deficiency of cortisol and aldosterone due to adrenal destruction; requires glucocorticoids ± mineralocorticoids.

Secondary adrenal insufficiency

Cortisol deficiency due to HPA axis suppression; aldosterone usually preserved.