Glucocorticosteroids Overview
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Questions and Answers

What is a primary consequence of long-term glucocorticoid (GCS) therapy on bone health?

  • Enhanced osteoblast activity
  • Increased bone density
  • Improved calcium absorption
  • Osteoporosis (correct)

    • Which mechanism contributes to osteoporosis in patients undergoing long-term GCS therapy?

  • Increased estrogen production
  • Suppression of osteoclast activity
  • Improved synthesis of gonadal steroids
  • Decreased calcium absorption from the gastrointestinal tract (correct)

    • What condition could result from prolonged use of glucocorticoids, characterized by joint pain?

  • Rheumatoid arthritis
  • Gout
  • Osteonecrosis (correct)
  • Osteoarthritis

    • What psychological effect is commonly observed in patients undergoing long-term GCS therapy?

    <p>Aggression and psychosis</p> Signup and view all the answers

    Which hormone's levels are affected due to long-term GCS therapy, contributing to osteoporosis?

    <p>Parathyroid hormone (PTH)</p> Signup and view all the answers

    What is a common physical manifestation of osteonecrosis associated with glucocorticoid therapy?

    <p>Pain in shoulder, knee or hip</p> Signup and view all the answers

    What negative effect does long-term glucocorticoid therapy have on the synthesis of hormones?

    <p>Inhibits gonadal steroid synthesis</p> Signup and view all the answers

    Which condition is NOT typically treated with glucocorticosteroids?

    <p>Diabetes</p> Signup and view all the answers

    What is the primary action of glucocorticosteroids in the body?

    <p>Mimicking the action of cortisol</p> Signup and view all the answers

    What is a common misconception about glucocorticosteroid treatment?

    <p>It provides a cure for autoimmune diseases</p> Signup and view all the answers

    In which scenario is the administration of glucocorticosteroids particularly beneficial?

    <p>Stimulating the synthesis of surfactant in premature neonates</p> Signup and view all the answers

    Under stressful conditions, how much glucocorticosteroids can the body produce daily?

    <p>20 to 300 mg</p> Signup and view all the answers

    For which of the following diseases are glucocorticosteroids used during exacerbations?

    <p>Multiple sclerosis</p> Signup and view all the answers

    What is one reason glucocorticosteroids are used in patients with renal disease?

    <p>To manage symptoms of an autoimmune component</p> Signup and view all the answers

    Which of the following statements is true regarding glucocorticosteroid use?

    <p>They may reduce respiratory distress in premature neonates</p> Signup and view all the answers

    What is the role of glucocorticosteroids (GCSs) in relation to phospholipase A2?

    <p>They suppress the synthesis of phospholipase A2.</p> Signup and view all the answers

    Which enzyme's synthesis is inhibited by glucocorticosteroids to prevent the formation of prostaglandins?

    <p>Cyclooxygenase-2</p> Signup and view all the answers

    What is the effect of exogenous glucocorticosteroids on the hypothalamic-pituitary-adrenal (HPA) axis?

    <p>They inhibit the HPA axis.</p> Signup and view all the answers

    Which hormone is released from the anterior pituitary gland in response to corticotropin releasing hormone (CRH)?

    <p>Adrenocorticotropic hormone (ACTH)</p> Signup and view all the answers

    How do glucocorticosteroids affect the immune system?

    <p>They suppress immune responses.</p> Signup and view all the answers

    What triggers the secretion of corticotropin releasing hormone (CRH) under normal conditions?

    <p>Stress, trauma, and diurnal rhythms</p> Signup and view all the answers

    Which factor directly influences the adrenal cortex to produce cortisol?

    <p>ACTH from the anterior pituitary gland</p> Signup and view all the answers

    What negative feedback effect occurs when exogenous glucocorticosteroids are administered?

    <p>Decreased synthesis of ACTH</p> Signup and view all the answers

    Which of the following cytokines is NOT mentioned as being affected by glucocorticosteroids?

    <p>IL-10</p> Signup and view all the answers

    What is the first step in the mechanism of action of glucocorticosteroids?

    <p>The glucocorticosteroid is transported in the bloodstream.</p> Signup and view all the answers

    What is the endogenous glucocorticoid produced by the adrenal cortex?

    <p>Cortisol</p> Signup and view all the answers

    What role do glucocorticoid response elements (GREs) play in the action of glucocorticosteroids?

    <p>They affect gene expression by facilitating transcription.</p> Signup and view all the answers

    Which proteins are responsible for trapping the glucocorticoid receptor in the cytoplasm?

    <p>HSP70, HSP90, and IP</p> Signup and view all the answers

    What happens to the glucocorticoid receptor upon binding to a glucocorticosteroid?

    <p>It undergoes a conformational change.</p> Signup and view all the answers

    What is the final structure formed when two glucocorticosteroid-glucocorticoid receptor complexes join together?

    <p>Dimer</p> Signup and view all the answers

    Which of the following statements accurately describes glucocorticosteroids' ability to influence gene expression?

    <p>They can induce or inhibit gene expression.</p> Signup and view all the answers

    What property allows glucocorticosteroids to easily cross the cell membrane?

    <p>Being lipid soluble</p> Signup and view all the answers

    What happens to heat shock proteins when a glucocorticosteroid binds to the receptor?

    <p>They get released from the glucocorticoid receptor.</p> Signup and view all the answers

    What term describes the specific molecules that glucocorticosteroids bind to within cells?

    <p>Glucocorticoid receptors</p> Signup and view all the answers

    Which of the following is a characteristic of glucocorticosteroids in relation to chronic conditions?

    <p>They assist in long-term management of chronic conditions.</p> Signup and view all the answers

    What is one way glucocorticosteroids suppress inflammation?

    <p>By increasing the synthesis of lipocortin-1 or annexin-1</p> Signup and view all the answers

    Which gene is stimulated by glucocorticosteroids and acts as an anti-inflammatory agent?

    <p>Lipocortin-1</p> Signup and view all the answers

    Which of the following cytokines is NOT inhibited by glucocorticosteroids?

    <p>IL-10</p> Signup and view all the answers

    What role do glucocorticosteroids play in the synthesis of glucose during stress?

    <p>They stimulate the transcription of glucose-generating genes</p> Signup and view all the answers

    Which of the following statements is true regarding cytokines affected by glucocorticosteroids?

    <p>Pro-inflammatory cytokines are inhibited</p> Signup and view all the answers

    Which transcription factor is closely associated with the action of glucocorticosteroids?

    <p>NF-ĸB</p> Signup and view all the answers

    Which process describes how glucocorticosteroids lead to less inflammation?

    <p>By decreasing the synthesis of inflammatory cytokines</p> Signup and view all the answers

    What is the primary effect of glucocorticosteroids on the energy levels of the heart and brain?

    <p>They ensure sufficient energy for function</p> Signup and view all the answers

    The synthesis of which enzyme is increased as a result of glucocorticosteroid activity?

    <p>Gluconeogenic enzymes</p> Signup and view all the answers

    What kind of genes are affected by glucocorticosteroids in terms of transcription?

    <p>Both inflammatory and metabolic genes</p> Signup and view all the answers

    Study Notes

    Glucocorticosteroids (GCS)

    • Potent anti-inflammatory agents
    • Explore effects on normal physiology
    • Relate normal effects to adverse drug reactions (ADRs)
    • Develop safe therapeutic approach
    • Consider adverse effects, adrenal suppression, and dose tapering

    Objectives

    • Understand GCS role in disease management
    • Describe GCS potency
    • Describe gene expression effects
    • Explain effects on normal physiology
    • Describe HPA axis effects (adrenal suppression/crisis)
    • Describe GCS effects on the immune system
    • Explain causes of adverse effects
    • Understand GCS use in asthma and other diseases

    Overview of Therapeutic Uses

    • Anti-inflammatory effects: Inflammatory bowel disease, inflammation, asthma
    • Immunosuppressive effects: Allergic reactions, organ transplantation, cancer, autoimmune diseases, rheumatic disorders, skin disorders

    Introduction to GCS Function

    • Endogenous and exogenous GCS
    • Normal levels: 10-20 mg/day; Stressed levels: 20-300 mg/day
    • Mechanism of action: bind cytoplasmic GCS receptor, affect gene expression via GCS response elements (GREs), induce/inhibit gene expression

    Mechanism of Action (detailed)

    • GCS transported in bloodstream by GCS-binding globulin (CBG)
    • Lipid-soluble, crosses cell membrane, enters cytoplasm
    • Receptor trapped by HSP70, HSP90, and immunophilin (IP)
    • Binding to GCS releases chaperone proteins
    • Forms dimer
    • Crosses nuclear membrane, binds GREs on DNA
    • Enables RNA polymerase binding, initiates transcription
    • mRNA processed, transported to cytoplasm
    • Protein synthesis, alters cellular function

    Glucocorticosteroids and Gene Transcription

    • GCSs reduce inflammation by decreasing inflammatory cytokine synthesis, increasing lipocortin-1 synthesis (inhibits phospholipase A2)
    • Examples of affected genes:
      • Stimulated: Lipocortin (annexin-1), gluconeogenic pathway enzymes
      • Inhibited: Cytokines (IL-1, IL-2, TNF-α, γ-interferon, IL-6), phospholipase A2, interleukin-2 receptor, cyclooxygenase-2

    Hypothalamic-Pituitary-Adrenal (HPA) Axis

    • Stress, trauma, and diurnal rhythms trigger CRH release from the hypothalamus
    • CRH stimulates ACTH release from the anterior pituitary gland
    • ACTH triggers cortisol release from the adrenal cortex
    • Exogenous GCSs suppress the HPA axis, reducing endogenous cortisol
    • Can lead to acute adrenal crisis (lack of cortisol) during stress, when using GCSs for extended periods (>14 days).

    Physiological Responses and Adverse Effects

    • Increased susceptibility to infections, cancer, diabetes, abnormal fat deposition
    • Increased protein and bone catabolism (muscle wasting, growth suppression, osteoporosis/osteonecrosis), mood changes, psychosis, aggression, depression
    • Increased gastric acid and pepsin secretion (potential gastric ulcers), sodium and water retention (hypertension, edema), potassium loss (muscle weakness)
    • Cushing's syndrome symptoms in prolonged use

    Factors Affecting Adverse Drug Reactions

    • Route of administration (parenteral > oral > site-specific)
    • Duration and dose
    • Alternate-day dosing (protects HPA axis, reduces adverse effects)
    • Mineralocorticoid activity
    • Drug formulation (first-pass metabolism: inhaled GCSs)

    Anti-Inflammatory on Skin and Effects on Immune System

    • Topical use: catabolic effects on collagen; potential for atrophy, striae, acneiform eruptions, fungal/bacterial infections & hypo-pigmentation
    • Topical GCS potency important: Clobetasol (strongest), Beclomethasone, Betamethasone, Mometasone, Fluticasone, Triamcinolone (moderate), Hydrocortisone (weakest).
    • GCSs suppress lymphocytes, monocytes, basophils, endothelial cells, cytokines, and inflammatory mediators (prostaglandins, leukotrienes)
    • General immune system suppression

    Glucocorticoid Use in Asthma

    • Inhaled GCSs are commonly used for asthma management (Beclomethasone, Budesonide, Fluticasone, Ciclesonide are preferred)
    • Systemic GCSs (Prednisone, Prednisolone, Methylprednisolone, Hydrocortisone) are used when inhaled GCSs are insufficient or in emergencies.
    • Common adverse effects of inhaled GCSs: oropharyngeal candidiasis
    • Less frequent but possible: cataracts, growth retardation, osteoporosis, easy bruising.
    • HPA axis and adrenal suppression is possible.

    Effects on Bone

    • Osteoporosis, inhibition of gonadal steroid synthesis, decreased Ca2+ absorption, increased PTH, suppression of osteoblast activity, risk of aseptic necrosis of joints.
    • High-dose, brief or prolonged therapy increases risk.

    Steroid Rage

    • Behavioral changes: aggression, psychosis, depression.
    • Not contraindicated in psychiatric illness but requires careful monitoring

    Dose Tapering

    • Important for long-term use (>2 weeks); a gradual decrease in dose is crucial.

    Monitoring for Immunizations

    • Delaying immunizations
    • Monitor blood glucose, blood pressure, and fluid status in patients receiving oral/IV high-dose GCS therapy

    Available Preparations (table-form)

    (Table format not supported, but you can refer to the provided pages, by looking at the table for preparation potency data)

    Topical Use Considerations

    • Potent topical GCSs should be reserved for severe dermatologic conditions.
    • Shorter treatment durations are preferred to minimize systemic effects.

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    Description

    This quiz examines glucocorticosteroids (GCS), focusing on their potent anti-inflammatory properties, effects on normal physiology, and related adverse drug reactions. Participants will explore the HPA axis, immune system implications, and therapeutic applications for diseases such as asthma and inflammatory conditions.

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