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 (B)</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) (A)</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 (A)</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 (B)</p> Signup and view all the answers

Which condition is NOT typically treated with glucocorticosteroids?

<p>Diabetes (C)</p> Signup and view all the answers

What is the primary action of glucocorticosteroids in the body?

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

What is a common misconception about glucocorticosteroid treatment?

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

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

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

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

<p>Multiple sclerosis (B)</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 (D)</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 (A)</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. (C)</p> Signup and view all the answers

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

<p>Cyclooxygenase-2 (D)</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. (C)</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) (C)</p> Signup and view all the answers

How do glucocorticosteroids affect the immune system?

<p>They suppress immune responses. (B)</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 (D)</p> Signup and view all the answers

Which factor directly influences the adrenal cortex to produce cortisol?

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

What negative feedback effect occurs when exogenous glucocorticosteroids are administered?

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

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

<p>IL-10 (C)</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. (A)</p> Signup and view all the answers

What is the endogenous glucocorticoid produced by the adrenal cortex?

<p>Cortisol (A)</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. (B)</p> Signup and view all the answers

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

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

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

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

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

<p>Dimer (A)</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. (B)</p> Signup and view all the answers

What property allows glucocorticosteroids to easily cross the cell membrane?

<p>Being lipid soluble (B)</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. (B)</p> Signup and view all the answers

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

<p>Glucocorticoid receptors (A)</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. (B)</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 (D)</p> Signup and view all the answers

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

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

Which of the following cytokines is NOT inhibited by glucocorticosteroids?

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

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

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

Which process describes how glucocorticosteroids lead to less inflammation?

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

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

<p>Gluconeogenic enzymes (A)</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 (B)</p> Signup and view all the answers

Flashcards

Glucocorticosteroids use

Glucocorticosteroids are used to suppress the immune system in various conditions like allergic reactions, organ transplantation, and inflammatory diseases (like IBD).

Glucocorticosteroids function

Glucocorticosteroid medications mimic the action of cortisol, a naturally occurring hormone in the body.

Glucocorticosteroids in stress

Under stressful conditions, the body may produce much more glucocorticosteroids--20-300mg per day.

Normal glucocorticosteroid production

The body usually produces around 10-20mg of glucocorticosteroids per day.

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Conditions using Glucocorticosteroids

These drugs are used to treat autoimmune diseases, rheumatic disorders, skin disorders and more. It also reduces respiratory distress in premature neonates.

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Glucocorticosteroids not curative

Using glucocorticosteroids does not cure underlying conditions.

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Adrenal insufficiency

A medical condition that requires glucocorticosteroids for treatment.

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Premature neonates and lungs

Glucocorticosteroids help the lungs of premature babies mature and reduce respiratory distress.

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Glucocorticosteroid mechanism

Glucocorticosteroids bind to receptors, affecting gene expression.

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Glucocorticoid receptor

A protein that binds glucocorticosteroids, altering gene expression.

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Gene expression

The process of turning genes on or off to create proteins.

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Glucocorticoid response elements (GREs)

DNA sequences where glucocorticoid receptors bind, affecting gene transcription.

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Cytoplasmic glucocorticoid receptor

A receptor located in the cell cytoplasm, waiting for the hormone.

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HSP70, HSP90, and IP

Proteins that bind to the receptor, preventing its movement to the nucleus.

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Confirmation change

Shape alteration of the receptor after hormone binding.

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Glucocorticoid binding globulin

Protein that carries glucocorticosteroids through the bloodstream.

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Lipid soluble

Can readily pass through cell membranes.

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Hormone dimerization

Two hormone-receptor complexes coming together.

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Glucocorticosteroids' action

Glucocorticosteroids bind to DNA, triggering mRNA transcription and increasing lipoprotein-1 synthesis, which inhibits inflammation by reducing inflammatory cytokine synthesis and increasing anti-inflammatory agent synthesis.

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Lipocortin-1/Annexin-1

An important anti-inflammatory agent, whose synthesis is stimulated by glucocorticosteroids, directly inhibiting phospholipase A2.

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Gluconeogenesis

The pathway for making glucose from various precursors stimulated by glucocorticosteroids during stress.

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Pro-inflammatory cytokines

Cytokines like IL-1, IL-2, TNF-α, and others whose transcription is inhibited by glucocorticosteroids.

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Glucocorticoid response elements

DNA sites where glucocorticosteroids bind to initiate gene transcription.

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Inflammation suppression

Glucocorticosteroids decrease the synthesis of inflammatory cytokines while increasing the synthesis of anti-inflammatory agents.

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Phospholipase A2

An enzyme inhibited by lipocortin-1/annexin-1, preventing the production of inflammatory mediators.

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GCS effect on genes

Glucocorticosteroids modify gene expression by stimulating or inhibiting transcription of different genes.

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GCS stress response

In times of stress, glucocorticosteroids prioritize energy for heart and brain function while stimulating glucose production.

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Transcription of mRNA

The process of producing mRNA from DNA, controlled by glucocorticosteroids and regulating protein synthesis.

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Catabolic effect on bone

Glucocorticosteroids (GCS) can weaken bones, leading to reduced bone density and increased fracture risk. This is due to their suppression of bone formation and promotion of bone breakdown.

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Iatrogenic Cushing syndrome

Prolonged use of GCS can mimic the effects of Cushing's disease, leading to symptoms like weight gain, high blood sugar, weakened bones, and increased risk of infections.

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Why does GCS increase susceptibility to cataracts?

Long-term GCS use increases the risk of cataracts by promoting oxidative stress and altering the lens proteins, leading to clouding of the eye lens.

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Increased skin absorption of GCS

GCS can penetrate the skin more easily than other medications, leading to increased absorption and potential for side effects.

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What is 'steroid rage'?

GCS therapy can cause mood swings, aggression, and even psychosis, as they affect the brain's neurotransmitter balance.

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Osteonecrosis

Prolonged GCS use can cause aseptic necrosis (death) of bone tissues, primarily in joints like shoulders, knees, and hips.

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How does GCS affect bone mineral density?

GCS suppress the production of sex hormones (estrogen and testosterone) which are essential for bone health, leading to decreased calcium absorption and increased bone resorption.

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Glucocorticosteroid (GCS) Action

GCSs mimic the action of cortisol, a naturally occurring hormone, by binding to receptors and influencing gene expression. This affects various cellular processes, leading to both anti-inflammatory and metabolic effects.

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GCS Anti-inflammatory Mechanisms

GCSs suppress inflammation by inhibiting the production of pro-inflammatory substances like prostaglandins and cytokines while promoting the synthesis of anti-inflammatory agents like lipocortin-1.

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How do GCS affect phospholipase A2?

GCSs inhibit phospholipase A2, an enzyme involved in inflammatory mediator production, by stimulating the synthesis of lipocortin-1, which directly blocks its activity.

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What is the HPA axis?

The hypothalamic-pituitary-adrenal (HPA) axis is a complex network that regulates stress responses and cortisol production. It involves the hypothalamus, pituitary gland, and adrenal glands.

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How do GCS affect the HPA axis?

Exogenous GCSs (those from medication) can suppress the natural HPA axis, leading to decreased cortisol production and potential side effects.

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GCS's Effect on Immune System

GCSs suppress the immune system, reducing inflammation and autoimmune reactions, but also increasing susceptibility to infections.

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What is gluconeogenesis?

Gluconeogenesis is the process of producing glucose from non-carbohydrate sources, like amino acids and glycerol, in the liver. GCSs stimulate this pathway to increase blood glucose levels.

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GCS and Diurnal Rhythm

The natural production of cortisol follows a diurnal rhythm, peaking in the morning and decreasing throughout the day. GCS medications can disrupt this pattern.

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GCS Prolonged Use: Side Effects

Long-term GCS use can lead to various side effects, including weight gain, bone thinning, mood changes, and increased risk of infections.

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Why are GCS sometimes necessary?

GCS are used in different medical conditions to suppress the immune system and reduce inflammation, such as allergic reactions, organ transplantation, and autoimmune diseases.

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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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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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