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PHAR 253 > Corticosteroids > Flashcards

Corticosteroids Flashcards

1
Q

What are the major hormones produced by the adrenal gland?

A

Mineralocorticoid (aldosterone), glucocorticoids (cortisol), and sex hormones (testosterone)

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2
Q

What are the two major parts of the adrenal gland?

A

Medula (inner portion) and Cortex (outer portion)

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3
Q

Where in the adrenal glands are its three major homones produced?

A

They are produced in the adrenal cortex. The cortex can be divided into 3 zonas.

Zona glomerulosa (mineralocorticoid)

Zona fascisculata (glucocorticoids)

Zona reticularis (sex hormones)

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4
Q

What are the functions of cortisol in the body?

A
  1. Mediate stress response (prepare body for stress via increased blood sugar, downregulate parasympathetic)
  2. Help regulate metabolism
  3. Help regulate inflammatory response and immune system
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5
Q

What is the HPA axis?

A

This system regulates production and secretion of cortisol.

Negative feedback loop

Hypothalamus–>Pituitary gland–>Adrenal gland

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6
Q

What are the most notable actions of glucocorticoids?

A

Supress inflammatory and immunological responses

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7
Q

What is the anti-inflammatory mechanism of action for corticosteroids?

A
  1. Altering cytokine release
  2. Blocking increased capillary permeability
  3. Lower vasoactive substances
  4. Inhibiting leukocyte and macrophage migration/adhesion
  5. Interfering with phagocytosis
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8
Q

What is the immunosuppressive mechanism of action for corticosteroids?

A
  1. Altering cell function of specific genes
  2. Affecting WBC function
  3. Inhibiting T-cell activation
  4. Inhibiting IL’s, cytokines, gamma-interferon, and TNF-alpha
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9
Q

What are some minor corticosteroid actions?

A
  1. Anti-mitotic activity
  2. Anti-tumour effects
  3. Anti-emetic effects
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10
Q

What is the most common way to sort corticosteroids into two categories?

A

Local vs. systemic agents

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11
Q

Why do patients prefer local agents over systemic corticosteroids?

A

Fewer side effects

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12
Q

What are the uses of Ophthalmic/Otic corticosteroids?

A

Used for: redness, itching, swelling, and pain

Commonly in combo with antibiotics

Available as drops, ointments, emulsions, intravitreal implants

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13
Q

What are some issues with Ophthalmic/Otic drops?

A

Incorrect delivery technique

45% of patients failed to get drops into the eyes

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14
Q

What are the uses of nasal inhaled corticosteroids?

A

Used for: Rhinitis, polyps, sinusitis

Issues with instillation technique

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15
Q

What are the uses of metered-dose corticosteroid inhalers?

A

Used for: mainstay for asthma

Very portable, but some patients may have incorrect inhalation technique

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16
Q

What is an advantage of inhaled dry powder corticosteoids vs. metered dose inhalers?

A

They list the number of remaining doses

Patient has to guess if they still have doses on a metered dose inhaler

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17
Q

What is the benefit of nebulizers as a delivery device?

A

Young children benefit from the mask fitting that can allow the administrator to release the drug into that closed space, allowing the child to breathe in the steroid easily

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18
Q

What are the goalpost corticosteroid products (based on potency)?

A
  1. Hydrocortisone (potency 7)
  2. Betamethasone valerate (potency 3)
  3. Betamethasone dipropionate (potency 2)
  4. Clobetasol propionate (potency 1)
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19
Q

What factors impact the efficacy of topical corticosteroids?

A
  1. Skin moisture
  2. Potency
  3. Formulation
  4. Application technique
  5. SIte (ex. hands vs. face)
  6. Skin condition
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19
Q

What are some corticosteroid rectal dosage forms

A
  1. Enemas
  2. Rectal Ointments
  3. Suppositories
  4. Rectal Foams

Used for: colitis, Crohn’s disease, hemmorhoids

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20
Q

What the types of injectable corticosteroids?

A
  1. Intravenous
  2. Intramuscular
  3. Intralesional
  4. Intra-articular
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21
Q

What are the advantages of intravenous corticosteroids?

A

Faster onset of effect

Useful when high doses are required

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22
Q

What are the usual sites of intra-articular corticosteroids?

A

hip, knee, ankle, shoulder, elbow, wrist

Do not inject more than 3-4 times per year

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23
Q

What are some qualities of oral corticosteroids?

A

They exhibit rapid and complete absorption from the gut

Oral doses are equivalent to IV due to quick absorption

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24
Q

What is the physiologic dose for corticosteroids?

A

This dose is supposed to replace deficiencies

5mg/day prednisone is approximately equivalent to the amount of cortisol secreted by the adrenal gland

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25
Q

What are the pharmacologic doses for corticosteroids?

A

These doses are meant to treat disease states and provide supportive therapy

5-15mg/day (low dose)

0.5mg/kg/day (moderate dose)

1-3mg/kg/day (high dose)

15-30mg/kg/day (massive dose)

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26
Q

Rank corticosteroid potency from least potent to most potent

A

Cortisone (lowest potency)

Hydrocortisone

Prednisone

Prednisolone

Methylprednisone

Triamcinolone

Dexamethasone

Betamethasone (highest potency)

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27
Q

What is the common starting oral corticosteroid?

A

prednisone

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28
Q

What are the side effects of ophthalmic corticosteroids?

A
  1. Stinging, redness
  2. Tearing, burning
  3. Secondary infection (due to immunosuppression)
  4. Glaucoma and cataracts
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29
Q

What some adverse events for patients that use corticosteroid oral inhalers?

A
  1. Thrush (rinse mouth to prevent)
  2. Hoarseness
  3. Dry mouth
  4. Dysphoria
  5. Difficulty swallowing
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30
Q

What are some side effects seen in patients that use corticosteroid nasal spray?

A
  1. Rhinnorhea
  2. Burning
  3. Sneezing
  4. Bloody nose (spray awy from septum to prevent)
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31
Q

What are some adverse effects seen in patients that use topical corticosteroids?

A
  1. Burning
  2. Irritation
  3. Skin atrophy
  4. Taxgyphylaxis (developing dose tolerance)
  5. Telangiectasia (spider veins)
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32
Q

What are some systemic complications associated with oral corticosteroid use?

A
  1. CNS (starts with euphoria, insomnia, restlessness. Can progress into depression, mania, and psychosis)
  2. Face/Back - Cushingoid features (Far redistribution from periphery to trunk)
  3. Ophthalmic (cataracts and glaucoma) More common in topical, but still a concern with oral dosage forms
  4. GI (take with food and do not take oral corticosteroid with NSAIDs due to ulcer risk)
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33
Q

What factors contribute to the severity of adverse effects while on corticosteroids?

A

High potency

High dose

High frequency

Long duration of therapy

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34
Q

What is the effect of corticosteroid use on blood glucose?

A

Increase in blood glucose due to corticosteroid induced gluconeogenesis and reduced glucose utilization by tissues

Elevated blood glugose can persist for months following discontinue

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35
Q

What is the effect of corticosteroids on blood pressure?

A

Corticosteroids with the greatest mineralocorticoid activity can cause increased fluid retention and subsequently elevate BP

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36
Q

What are the effects of corticosteroids on appetite?

A

Increases appetite

Especially beneficial for cancer patients who have lost their appetite

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37
Q

What are the effects of corticosteroids on growth?

A

Dose-dependent and most pronounced with oral therapy

Multiple mechanisms (decreasing osteoblasts, decreased growth hormone secretion)

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38
Q

What is the HPA-Axis?

A

A connection between the brain and adrenal glands

It is the body’s main stress system

39
Q

When are endogenous levels of cortisol the highest?

A

They are highest in the morning and are at their lowest at midnight

Cortisol levels can jump 10x in period of acute stress

40
Q

In a patient with HPA-Axis suppression, what will happen if corticosteroid therapy is abrupty stopped?

A

They will experience adrenal insufficiency. They symptoms are the opposite of too much cortisol

  1. Hypotension
  2. Hypoglycemia
  3. Flu-like symptoms
  4. Weight loss
  5. Confusion
41
Q

What factors affect the severity of HPA-Axis suppression?

A

Dose

Administration

Potency

Interval (10mg QID is not the same as 40mg OD)

Route of administration

Time of administration (usually taken in the morning)

42
Q

Can we easily predict which patients will experience HPA-axis suppression?

A

Not really

But patients on dosed of over 15mg/day will most likely experience HPA-axis suppression

43
Q

How long can it take for HPA-axis suppression to reverse and cortisol production to return to normal?

A

It depends on the unique situation of each patient. But on average it can be between 1 to 3 years after cessation of exogenous steroids

44
Q

What are the side effects of corticosteroids on the immune system?

A

Impair antibodies and phagocytosis

Susceptibility to viral infections (varicella zoster), bacterial infections (cellulitis), fungal infections (candida)

45
Q

What are the side effects of corticosteroids on the skin and connective tissue?

A

Inhibit epidermal cell division and DNA synthesis

Thin skin

Striae

Acne (can occur following short course of corticosteroids)

46
Q

What are the effects of corticosteroids on the bones?

A

Bone loss with corticosteroids occurs most rapidly in the first 3 months

30-50% will develop osteoporois with chronic treatment

Risk of fracture increases with doses as low as 2.5-7.5mg/day

47
Q

What is the effect of corticosteroids on muscle tissue?

A

Muscle weakness due to decreased protein synthesis in the muscle

48
Q

What are the most common side effects seen in children who are on corticosteroids chronically?

A
  1. Weight gain
  2. Growth retardation
  3. Cushingoid features

Infection is the most serious adverse effects

49
Q

What are the most common side effects seen in short course corticosteroid therapy in children?

A
  1. Vomiting
  2. Behavourial changes
  3. Sleep disturbances
50
Q

What is the use of corticosteroids in COVID-19 therapy?

A

Improve clinical outcomes and decrease mortality in hospitalized patients requiring oxygen

51
Q

Are corticosteroid doses standardized?

A

No there are no set guidelines

Dosing is up to prescriber preference and comfort level

Need to balance disease activity and toxicity

52
Q

Are corticosteroid doses tapered when ending therapy?

A

Corticosteroids need to be tapered upon discontinuation if HPA-axis suppression is suspected

Tapering is usually done if patient has been on corticosteroid therapy for longer than 3 weeks (reduce 5mg every 3-7 days)

53
Q

Refer to page 77-78 for Alternate Day Dosing for corticosteroids

A
54
Q

Do patients that undergo high stress situations need to adjust corticosteroid dose?

A

Yes, but only in situations like moderate illness and surgery.

HC is given for a few days and is tapered rapidly

55
Q

What is the utility of steroid pulse therapy?

A

short term and high dose steroids can be given in situations where rapid remission of serious conditions is desired

ex. juvenile rheumatoid arthritis, nephrotic syndrome

56
Q

What are the advantages of steroid pulse therapy?

A
  1. More rapid control of condition
  2. Helps prevent adverse effects from prolonged steroid therapy
57
Q

What are some disadvantages of steroid pulse therapy?

A
  1. Hypertension
  2. Infection
  3. Siezure
  4. Psychosis
58
Q

Do corticosteroid adverse effects disappear once discontinued?

A

They do not go away immediately, but it can take months for patient to fully recover

59
Q

What is the effect of aldosterone?

A

Na+ and water retention (helps increase BP)

K+ excretion

60
Q

What is the main androgen secreted by the adrenal gland?

A

DHEA

It is the primary source of androgens in women

61
Q

What causes Cushing’s syndrome?

A

A disorder caused by persistant exposure to excesive glucocorticoids (exogenous or endogenous)

62
Q

Is endogenous overproduction of cortisol the leading cause of Cushing’s syndrome?

A

No, endogenous overproduction of cortisol is a very rare disorder (1-10 in a million)

1% of the population uses exogenous glucocorticoids, but 10% of these patients have Cushing’s syndrome

63
Q

Are women more affected by Cushing’s syndrome than men?

A

Yes, women are almost 5 times more likely to have Cushing’s syndrome

64
Q

What is the etiology of endogenous overproduction of cortisol?

A
  1. ACTH dependent (80%):
    A benign pituitary tumour over produces ACTH which stimulates production of cortisol in the adrenal glands
  2. ACTH independent (20%):
    Adrenal gland tumours
65
Q

Is Cushing’s syndrome easy to diagnose?

A

No, it is often difficult and delayed because it mimic other conditions

66
Q

How is Cushing’s syndrome diagnosed?

A
  1. Establish if hypercortisolism is present (Urine free of cortisol, midnight serum cortisol, and low-dose dexamethasone suppression test)
  2. Establish the cause (HIgh dose dexamethasone suppression test, Plasma ACTH via radioimmunoassa, etc.)
67
Q

What are some common clinical features associated with Cushing’s syndrome?

A

Obesity

Rounded face

Growth retardation in children

Depression/emotional lability

Decreased libido

68
Q

What are some signs that can help distinguish obesity symptoms of Cushing’s syndrome from regular obesity?

A
  1. Protein wasting (Thin skin, unusual bruising, muscle weakness)
  2. Suddenly apearing striae
69
Q

What are the therapeutic goals in Cushing’s syndrome?

A
  1. Remove the source of hypercortisolism
  2. Restore secretion to normal
  3. Reverse clinical features
  4. Prevent dependency on medications
70
Q

What are the consequences of leaving Cushing’s syndrome untreated?

A

5 yr survival rate of 50%

With appropriate treatment most signs will resolve within 2-12 months

71
Q

What are some treatment options for Cushing’s syndrome?

A

Surgery is the main treatment option in Cushing’s syndrome

Pituitary adenoma and adrenal tumours can be removed

Ectopic ACTH syndrome (multiple tumour sites): most need drugs following surgery

For drug induced Cushing’s syndrome, taper off corticosteroids

72
Q

What is the utility of pharmacological therapy for Cushing’s syndrome?

A
  1. To decrease cortisol levels before surgery
  2. As adjunct treatment after unsuccessful surgery or radiation
  3. For tumours that cannot be removed easily
  4. To help treat severe symptoms
73
Q

What are some examples of pharmacological agents used in the treatment of Cushing’s syndrome?

A

Steroidogenesis Inhibitors:
1. Ketoconazole
2. Metyrapone
3. Mitotane

ACTH secretion inhibitors:
Pasireotide

74
Q

How does ketoconazole work to treat Cushing’s syndrome?

A

Blocks the synthesis of cortisol in the adrenal gland

Ketoconazole is the drug of choice (effective and side effect profile is not as bad as the other agents)

200-400mg TID

75
Q

Does ketoconazole have many drug interactions?

A

Yes

Ketoconazole has drug interactions with a diverse set of drugs

76
Q

How does Metyrapone treat Cushing’s syndrome?

A

Inhibits conversion of precursor molecule into cortisol

Commonly used if experiencing dose limiting SE effect with ketoconazole OR adjuct therapy with ketoconazole

Androgenic side efffcts (hirsutism and acne)

77
Q

How does Mitotane treat Cushing’s syndrome?

A

Greatly decreases cortisol synthesis

Used for inoperable adrenal carcinoma and usually started in hospital

78
Q

Are steroidogenic inhibitors effective in long-term therapy of Cushing’s syndrome?

A

Not effective as monotherapy, but often used in combo with interventions like surgery and radiation

79
Q

How does pasireotide treat Cushing’s syndrome?

A

Inhibits ACTH secretion in ACTH-producing adenomas

This drug is used when surgery has been ruled out

It is not commonly used because it has too many side effects and not effective enough

80
Q

What is Addison’s Disease (Primary adrenal insufficiency)?

A

A rare disorder in which the adrenal glands cannot synthesize enough glucocorticoids and mineralocorticoids

(all 3 zones of the adrenal cortex have been destroyed)

81
Q

What causes Addison’s Disease (Primary Adrenal Insufficiency)?

A
  1. Autoimmune mediated destruction of the adrenal cortex (common in the Western world)
  2. Infectious diseases like TB, HIV, CMV (more common in developing world)
  3. Hemorrhage (bleeding into the adrenal glands)
  4. Injury to adrenal glands
82
Q

What is secondary adrenal insufficiency?

A

It is caused by a decrease in the amount of cortisol/corticosteroids in the body

  1. Abruptly stopping corticosteroids
  2. Pituitary and hypothalmic tumours
  3. Surgical removal of pituitary
  4. Other medications
83
Q

What are some signs and symptoms of adrenal insufficiency?

A
  1. Fatigue (95%)
  2. Weight Loss (76%)
  3. Hypotension
  4. Skin hyperpigmentation (usually the first symptom)
84
Q

What causes hyperpigmentation in adrenal insufficiency?

A

In adrenal insufficiency, a not a lot of ACTH is converted into cortisol. This results in a buildup of ACTH.

ACTH will bind to melanocytes and overstimulate them into developing more than usual melanin

(most prominent on sun-exposed areas, knuckles, elbowsm knees, mucous membranes)

85
Q

Is adrenal insufficiency easy to diagnose?

A

Patients experience non-specific symptoms, so diagnosis can be difficult to ascertain

These symptoms will build up gradually

86
Q

How is adrenal insufficiency diagnosed?

A
  1. Clinical presentation
  2. Lab tests
  3. Cortisol levels
  4. Medical Imaging
87
Q

What are the treatment options for adrenal insufficiency?

A

Required daily glucocorticoid and mineralocorticoid replacement

ex. Hydrocortisone(gluco.) and Fludricortisone(mineralo.)

88
Q

Why is hydrocortisone the glucocorticoid drug of choice in adrenal insufficiency?

A

It is preferred because of its good glucocorticoid and mineralocorticoid activity

10-15mg/day (2/3 at 8am, 1/3 at noon)

89
Q

How do practitioners know their treatment plan for adrenal insufficiency is working?

A

Reduction in hyperpigmentation is a good sign

No longer loosing weight, blood pressure is returning to normal

90
Q

Do patients with adrenal insufficiency need to take supplemental stress dosing?

A

Yes, they need to give themselves an extra dose after experiencing stress. This is why patients with adrenal insufficiency should carry an extra dose on hand.

  1. Strenous activity (add 5-10mg HC)
  2. Minor febrile illness or trauma (double dose until recovery)
  3. Emergency self-treatment necessary (HC 75-300mg/day IM)
91
Q

What is a consequence of adrenal insufficency that women uniquely experience?

A

The adrenal glands produces majority of the androgens produced in a woman’s body

Loss of androgen supply can be supplemented with DHEA 25-50mg/day

92
Q

What is acute adrenal crisis?

A

This is a medical emergency following a rapid decrease in cortisol/corticosteroid levels

Due to abrupt steroid withdrawal or lack of appropriate stress-dosing

93
Q

How are acute adrenal crises treated

A

Parenteral glucocorticoids for rapid gluco. delivery

Hydrocortisone IV is the drug of choice in acute adrenal crises

94
Q

What are some important patient education points in adrenal insufficiency?

A
  1. Seriousness of disease
  2. Importance of adherance
  3. Medication effects/ side effects
  4. Have extra meds or glucocorticoid injection on hand
  5. Recognizing worsening of condition
  6. Importance of wearing Medic Alert bracelet
95
Q
A

PHAR 253 (10 decks)

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