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Pharmacology > Corticosteroids > Flashcards

Corticosteroids Flashcards

1
Q

Corticosteroids Examples

A
  • Betamethasone
  • Cortisone
  • Dexamethasone
  • Fludrocortisone (mineral-)
  • Hydrocortisone
  • Metylprednisolone
  • Prednisolone
  • Prednisone
  • Triamcinolone
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2
Q

Classification of steroids

A

1- Corticosteroids
- Gluco- (Anti-inflammatory)
- Mineralo- (Water retention)
2- Sex hormones
- Estrogens Estradiol
- Androgens Testosterone
- Progestins

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3
Q

Inhibitors of adenocorticoid

A
  • Eplerenone
  • Ketoconazole
  • Spironolactone
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4
Q

Natural body corticosteroids

A
  • Gluco: Cortisol
  • Mineral: Aldosterone
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5
Q

Hypothalamic–pituitary–adrenal axis

A

In order
- Hypothalamus
CRH
- Pituitary
ACTH
- Adrenal
Cortisol ( - feedback on Hypothalamus & Pituitary)

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6
Q

2 types of treatment

A

1- Pulse Therapy:
- Sinus rhythm
- Strengthens gland (Delayed puberty)
2- Non-stop Therapy:
- Constant drug, keep level
- Negative feedback
- Antagonistic & inhibitory

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7
Q

Cortisol rhythm

A
  • 8 am most, darkness least
  • Night sensitivity most, 8 am least
  • Drug works best at night with food
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8
Q

Corticosteroids Biosynthesis

A

Cholesterol –> Pregnenolone –>
1- Mineral- pathway
- Progesterone
- 11-Deoxy-corticosterone
(11B-Hydroxylase)
- Corticosterone
- Aldosterone
2- Gluco- pathway
(17a hydroxylase)
- 17-Hydroxy-Pregnenolone
- 17-Hydroxy-Progesterone
- 11B-Deoxycortisol
- Cortisol
3- Androgen & esterogen pathway
- 17-Hydroxy-Pregnenolone
- Dehydroepi-androsterone
- Androstene-3,17-dione
- Testosterone
- Estradiol

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9
Q

Steroids inside cell (mechanism of action)

A
  • CBG (Just for bodily steroids)
  • HSP90 Complex (w/ Receptor)
  • Steroid comes, HSP90 goes, Receptor-steroid dimer, goes inside nucleus
  • Affects DNA
  • Transcription
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10
Q

Immunosuppressive effects

A
  • Cell-mediated immunity
  • Lymphocytes
  • Lymphotoxic –> Hematologic cancers
  • After Organ Transplants
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11
Q

Anti-inflammatory effects

A
  • Dramatic effect on numerous processes
  • Increase neutrophils
  • Decrease lymphocytes, eosinophils, basophils & monocytes
  • Inhibit leukocyte migration
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12
Q

Metabolic effects

A
  • Gluconeogenesis so glucose rise
  • Lipolysis, Lipogenesis so fat deposition increase
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13
Q

Catabolic effects

A
  • Muscle protein catabolism
  • On bone: osteoporosis
  • Children: reduced growth
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14
Q

Other effects

A
  • Cortisol needed for natural kidney water excretion
  • Glucocorticoid high doses can cause deep behavioral changes
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15
Q

Hydrocortisone

A
  • Synthetic Cortisol
  • Has circadian rhythm
  • Cortisol is 95% bound to CBG
  • Good oral absorption after food
  • 10-14d needs tapering
  • Liver clearance
  • Absorbed by damaged skin, not normal skin
  • Small but significant mineral- effect
  • Hypertension in Cortisol or ACTH secreting tumors (Cushing’s)
  • 1h gluco-, 1h mineral-
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16
Q

Glucocorticoids lengths of effect

A

Short acting (1-12h):
- Hydrocortisone
- Cortisone
Intermediate acting (12-36h):
5-6×, normal skin
- Prednisone
- Prednisolone
- Metylprednisolone
- Triamcinolone
Long acting (36-55h):
single dose/d, dexa 0.5=prednisolone 50, normal skin
- Betamethasone 36-55h
- Dexamethasone 24-36h

17
Q

Beclomethasone, Budesonide, Fluticasone

A
  • Inhalant glucocorticoid (Aerosol inhaler)
  • Asthma
  • No oral & little lung absorption
  • Bronchodilator
  • No height loss (only 2-3cm later)
  • Little systemic and toxic effect
    Fluticasone has longer half life
  • Nasal spray for nose inflammation
18
Q

Different dosage forms

A
  • Eye drops
  • Otic drops
  • Ophthalmic ointment
  • Lotions
    Can use eye for ear / eye and ear drop for skin but NOT the reverse
19
Q

Clinical uses

A

1- Adrenal disorders
2- Non-adrenal disorders

20
Q

Adrenal disorders

A

1- Addison’s (adrenal insufficiency): Pulse therapy
2- Cushing’s: Non-stop therapy

21
Q

Non-adrenal disorders

A
  • Inflammatory & immunologic disorders (asthma, organ transplant rejection, collagen diseases, Rheumatic disorders)
  • Hematopoietic cancers
  • Neurologic: Dexa in MS
  • Chemo-induced vomiting: Dexa
  • Hypercalcemia
  • Mountain sickness
  • Premature labor: Betamethasone hastens maturation of fetal lungs 2w before term
22
Q

Toxicity & Side effects

A
  • <2w is well tolerated, tapering if longer
  • Decreased growth
  • Glaucoma
  • Osteoporosis
  • Impaired wound healing & increased risk of infection
  • Increased risk of diabetes
  • Appetite
  • Hypertension
  • Hypokalemia
  • Peripheral edema
  • Emotional disturbance, euphoria, depression, Psychosis
23
Q

Minimizing toxicity

A
  • Local application
  • Alternate-day therapy (reduce Pituitary suppression)
  • Tapering (even for months)
  • To avoid adrenal insufficiency, additional stress doses during serious illnesses or before surgery
24
Q

Mineralocorticoids

A
  • Aldosterone
  • Fludrocortisone
  • Deoxycorticosterone (vet usage)
25
Q

Aldosterone

A
  • Regulation by ACTH & renin-angiotensin system
  • Important for blood volume & pressure
  • Short half-life
  • Little gluco- activity
26
Q

Fludrocortisone

A
  • Significant gluco- activity
  • 10h gluco-, 125h! mineral-
  • Hormone replacement therapy (Cushing’s & Pituitary removal)
27
Q

Corticosteroid antagonists (inhibitors)

A

1- Receptor Antagonists:
- Spironolactone
- Eplerenone
- Mifepristone
2- Synthesis Inhibitors:
- Ketoconazole
- Aminoglutethimide
- Metyrapone
- Etomidate

28
Q

Spironolactone & Eplerenone

A
  • Antagonists of Aldosterone
  • Lower blood volume & pressure
  • Eplerenone mostly on aldosterone but spironolactone on endrogens too
  • In Hirsutism
  • Side effects: Hyperkalemia, Gynecomastia (NOT Eplerenone)
29
Q

Mifepristone (RU-486)

A
  • Progesterone receptor antagonist –> Cushing’s & Abortion
  • Glucocorticoid receptor antagonist
30
Q

Ketoconazole

A
  • Antifungal
  • Inhibits CYP450 (necessary for steroid synthesis)
  • INDICATION: steroid reduction
  • Adrenal carcinoma
  • Hirsutism
  • Breast & prostate cancer
  • Side effects: Liver dysfunction, CYP450 interaction with lots of drugs
31
Q

Aminoglutethimide

A
  • Blocks cholesterol to pregnenolone conversion
  • INDICATION: Steroid-producing adrenocortical cancer
32
Q

Metyrapone

A
  • Inhibits normal synthesis of Cortisol, NOT the precursors
  • INDICATION: Diagnostic tests of adrenal function
33
Q

Etomidate

A
  • General anesthetic
  • Inhibits 11B-Hydroxylase (Corticosterone & Cortisol)
  • INDICATION: Cushing’s
34
Q

Prednisolone

A
  • Activates gluco- receptor
  • USES: Inflammatory, organ transplant, Hematologic cancer
  • Interactions: Adrenal suppression

Pharmacology (6 decks)

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