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PHPY 305 > Corticosteroids > Flashcards

Corticosteroids Flashcards

1
Q

Corticosteroids fall into two categories

A

Glucocorticoids: have significant metabolic effects including carbohydrate metabolism
- example: cortisol
- far more glucocorticoids are used so corticosteroids and glucocorticoids are often used interchangeably
Mineralocorticoids: Have effects on electrolytes
- example: aldosterone

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2
Q

Cortisol

A
  • major endogenous glucocorticoid
  • follows a circadian rhythm
  • Peaks in the morning, troughs around midnight
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3
Q

Aldosterone

A
  • Major endogenous mineralocorticoid

- regulates sodium, water balance

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4
Q

How is cortisol generated?

A

Through hypothalamic pituitary axis

  • hypothalamus secretes corticotrophin releasing hormone
  • acts on anterior pituitary which then releases Ardeno-corticotrophin hormone which acts on the adrenal cortex that release cortisol
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5
Q

Beneficial effects of glucocorticoids

A
  • anti-inflammatory
  • immunomodulating
  • anti-proliferative effects
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6
Q

Glucocorticoids mechanism

A
  • reduce expression of PLA2

- inhibit both the COX and lipoxygenase pathways

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7
Q

Glucocorticoids side effects

A
  • osteoporosis
  • Psychiatric (euphoria, depression)
  • Peptic ulcer
  • many metabolic effects
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8
Q

Metabolic effects of Glucocorticoids

A
  • Proteolysis
  • increased gluconeogenesis: hyperglycemia, diabetes
  • increased lipolysis: obesity, fat redistribution
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9
Q

Effects of excess Cortisol

A

Cushing’ Disease

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10
Q

Cushing’s Disease

A

Disorder of excess cortisol, caused by: Adenoma (pituitary/adrenal) excess ACTH
- Or by Iatrogenic reasons (use of glucocorticoids)

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11
Q

Cushing’s disease signs and symptoms

A
  • Lipolysis: Fat redistribution - moon face, buffalo bump
  • Proteolysis: muscle wasting
  • increased glucose: diabetes Mellitus
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12
Q

Effects of GC withdrawal

A
  • excess GC administration over a long period of time can lead to reduced cortisol secretion
  • negative feedback
  • lead to withdrawal when discontinued: acute adrenal insufficiency or Addisonian Crisis
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13
Q

GC adverse effects

A

GC’s can inhibit production of ACTH which halts cortisol secretion

  • occurs as little as 2 weeks therapy/year
  • If HPA axis is suppressed
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14
Q

Symptoms of GC withdrawal

A
  • Fever
  • Myalgia
  • Arthralgia
  • Malaise
  • Serious: Addisonian Crisis, only seen with high doses or long duration of therapy
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15
Q

Addisonian Crisis Causes

A
  • caused by acute deficiency in cortisol secretion: life threatening, patients are often in shock
    Primary cause: impairment of adrenal cortex due to serious illness
    Secondary cause: Iatrogenic (corticosteroid withdrawal)
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16
Q

Addisonian Crisis management

A

Oral or intravenous glucocorticoids

17
Q

Corticosteroids and the HPA axis, how to reduce risk of withdrawal

A

Reduce dose in increments every few days

  • Example Prednisone 25mg daily
  • reduce by 5mg every three days
18
Q

Pharmacokinetics of GCs

A
  • well absorbed orally
  • other routes to minimize adverse effects
  • the biological half life is longer than the elimination half-life
  • have effects on gene expression that persist after they are eliminated
  • Mainly eliminated via hepatic metabolism
19
Q

Potencies of GCs and MCs

A 
GCs effects (anti-inflammatory)
MCs effects (Salt-retaining)
20
Q

Glucocorticoids examples (4)

A

Cortisol
Prednisone
Triamcinolone
Dexamethasone

21
Q

Mineralocorticoids examples (2)

A

Aldosterone

Fludrocortisone

22
Q

Glucocorticoids agonists

A

Short acting: Cortisol
Intermediate acting: Prednisone
Long acting: Dexamethasone

23
Q

Mineralocorticoid agonists

A

Fludrocortisone

24
Q

Corticosteroids (Oral)

A

Dexamethasone: uses Nausea/vomiting (raised intracranial pressure)
Prednisone: Uses - IBD, Astham/COPD, etc
Significant side effects

25
Q

Topical Corticosteroids

A

Hydrocortisone: used for rash, pruritus

Key side effects: thinning of skin, minimal systemic absorption

26
Q

Inhaled Corticosteroids

A

Fluticasone: inhaled reduces risk of systemic side effects
- used primarily for their anti-inflammatory effects
Key side effects: Opportunistic Infection: Oral thrush, Due to local immune suppressant effect
- also used intranasally for Allergic Rhinitis

27
Q

Corticosteroid Inhibitors (Inhibit Synthesis)

A

Metyrapone: inhibits 11-beta hydroxylase which inhibits deoxycorticosterone conversion one corticosterone (no aldosterone) and inhibits 11-deoxycortisol from conversion to Cortisol
Ketoconazole: inhibits CYP450
- both for the treatment of Cushing’s Disease

28
Q

Corticosteroid Inhibitors (Receptor Antagonist)

A

Mifepristone (RU486): also an abortifacient

- for the treatment of Cushing’s syndrome

PHPY 305 (14 decks)

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