by mtoom


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  • What is the chief glucocorticoid in humans?
  • What is the chief mineralocorticoid in humans? 
  • Gluco: Cortisol
  • Mineralo: Aldosterone 
With steroids, what is meant by "delay to effect"?
Time to onset for most effects is several hours
  • Because effects on gene transcription must take place 
With steroids, what is meant by "hit and run"?
Most effects persist beyond drug clearance
  • Difference between biological and elimination halflife 
When a patient is given cortisol as a therapy, the physician refers to it as what?
Hydrocortisone
How much cortisol is secreted under normal physiological conditions in a day? **
10 mg/d
Which potency of a steroid translates into anti-inflammatory effects?
Glucocorticoid potency

(as opposed to the mineralocorticoid potency)
Which steroid is used only for the mineralocorticoid effects?
Fludrocortisone
Describe 3 ideal characteristics of inhaled steroids?
  • High topical potency
  • Low oral bioavailability
  • Rapid systemic inactivation 
Name 4 inhaled steroids, what is the most well-known one?
  • Fluticasone (Flovent)
  • Budenoside
  • Ciclesonide
  • Beclomethasone
  • Cortisol is highly bound to what in serum?
  • Synthetic steroids are bound to what in serum? 
  • Cortisol binds CBG
  • Synthetic steroids bind albumin
Summarize what is important to understand about drug design and synthetic steroids.
  • They have differential activity on glucocorticoid versus mineralocorticoid receptors.
  • They have different potencies for each receptor.
  • Glucocorticoid activity translates into anti-inflammatory activity.
How is hydrocortisone (cortisol) dosed?
To mimick physiological diurnal variation.
  • 10mg/morning
  • 5mg/evening
How are topical steroids categorized?
(sort of random but emphasized in lecture)
Vasoconstriction potency
How to determine the size of a steroid dose?
Always use the minimal dose required to achieve any effect
  • Do not try to increase dose to eliminate symptoms
  • Determined dose by trial and error but start low
How do steroids work in anaphylaxis? (2)
  • Permissive effects on epinephrine
  • Anti-inflammatory effects via glucocorticoid receptors
What is the most important effect of mineralocorticoids?
Na+ retention
When steroids are given systemically, what is the most common route?
Oral (~80%)
What are 3 ways to give steroids?
  • Systemic
    -oral, iv, im 
  • Inhaled
  • Topical
    -skin, intra-articular, mucosa 
What is the overall effect of topical steroids?
Catabolic effect
What is a common problem with topical steroids? Explain.
Tolerance
  • Occurs after regular administration for 4-5 days 
Summarize the metabolism and excretion of steroids.
  • Hepatic/extrahepatic reductions
  • Hepatic conjugation
  • Excretion via urine
What are the 2 types of therapeutic uses of steroids?
  • Endocrine
  • Non-endrocrine
  • Give 3 examples of endocrine usage of steroids.
  • When might a dose need to be temporarily increased
  • Chronic adrenal insufficiency
    -hydrocortisone
    -fludrocortisone
  • Acute adrenal insufficiency
    -hydrocortisone 
  • Congenital adrenal hyperplasia
    -fludrocortisone

Must 2x/3x the dose during infection.
Give examples of non-endrocrine disorders requiring steroids (12)
  • Rheumatic/autoimmune
  • Anaphylaxis
  • Bronchial asthma
  • IBD
  • Renal
  • Dermatologic
  • CNS
  • Opthalmologic
  • Organ transplant
  • Neoplastic
  • Prenatal lung maturation in preterm infants
  • Postoperative nausea and vomiting prophylaxis
What is the prototype drug for dealing with inflammation in nonendocrine disorders?
Prednisolone
  • In bronchial asthma, what is the mainstay of regular therapy?
  • What are the effects of this therapy?
  • Inhaled corticosteroids
  • Effects:
    -relieve persistent symptoms
    -improve pulmonary function
    -reduce asthma-associated morbidity
How much of the dose of an inhaled corticosteroid reaches the respiratory tract?
Under optimal conditions:
  • 10-20% 
  • How common are systemic/local side effects of inhaled corticosteroids?
  • What are the local side effects? (2) 
  • Systemic side effects: rare
    Local side effects: infrequent
     
  • Local side effects:
    -Oropharyngeal candidiases
    -Dysphonia 
  • What 2 major changes of asthma are reduced by inhaled corticosteroids?
  • Inflammatory changes
    -steroids inhibit cytokine production
    -steroids directly inhibit inflammatory cells
  • Airway hyperresponsiveness
When should long-term steroids be started?
Only when absolutely indiciated
What problems can happen due to glucocorticoid withdrawal? (3)
  • Acute adrenal insufficiency
    -HPA axis is impaired if treated for more than 2 weeks in previous year
    -HPA axis recovery takes weeks/months up to 1 year
    -Slow tapering of dose is critical
  • Flare-up of disease
  • Glucocorticoid withdrawal syndrome
    -fever
    -myalgia
    -arthralgia
    -malaise 
Name 2 strategies to minimize iatrogenic Cushing's
  • Alternate-day therapy
    -Total 48 hour dose every other morning 
  • Pulse therapy 
What must be screened for in patients on long-term glucocorticoids?
  • Infection: TB
  • Cataract, peptic ulcer disease, psychological disorders
  • Monitor K+, glucose, blood pressure and weight
  • Minimize osteoporosis
    -HRT
    -Ensure high Ca2+ intake +/- supplemental vitamin D 
For long-term steroid patients undergoing major surgery, what do you need to do?
Subtitute therapy (for any patient with more than 2 weeks steroid use in past year)
  • Give cortisol with anesthesia 
Name 5 inhibitors of glucocorticoid synthesis
  • Aminoglutethimide
    -P450 inhibitor
  • Metyrapone
    -P450 inhibitor
  • Ketoconazole
    -P450 inhibitor
  • Finasteride
    -5α-reductase inhibitor
  • Etomidate
    -P450 inhibitor
Name 1 inhibitor of glucocorticoid action
  • Mifepristone
    -progesterone receptor blocker
    -glucocorticoid receptor blocker
    -used to terminate pregnancies 
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