Corticosteroids Flashcards
Corticosteroids Examples
- Betamethasone
- Cortisone
- Dexamethasone
- Fludrocortisone (mineral-)
- Hydrocortisone
- Metylprednisolone
- Prednisolone
- Prednisone
- Triamcinolone
Classification of steroids
1- Corticosteroids
- Gluco- (Anti-inflammatory)
- Mineralo- (Water retention)
2- Sex hormones
- Estrogens Estradiol
- Androgens Testosterone
- Progestins
Inhibitors of adenocorticoid
- Eplerenone
- Ketoconazole
- Spironolactone
Natural body corticosteroids
- Gluco: Cortisol
- Mineral: Aldosterone
Hypothalamic–pituitary–adrenal axis
In order
- Hypothalamus
CRH
- Pituitary
ACTH
- Adrenal
Cortisol ( - feedback on Hypothalamus & Pituitary)
2 types of treatment
1- Pulse Therapy:
- Sinus rhythm
- Strengthens gland (Delayed puberty)
2- Non-stop Therapy:
- Constant drug, keep level
- Negative feedback
- Antagonistic & inhibitory
Cortisol rhythm
- 8 am most, darkness least
- Night sensitivity most, 8 am least
- Drug works best at night with food
Corticosteroids Biosynthesis
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
Steroids inside cell (mechanism of action)
- CBG (Just for bodily steroids)
- HSP90 Complex (w/ Receptor)
- Steroid comes, HSP90 goes, Receptor-steroid dimer, goes inside nucleus
- Affects DNA
- Transcription
Immunosuppressive effects
- Cell-mediated immunity
- Lymphocytes
- Lymphotoxic –> Hematologic cancers
- After Organ Transplants
Anti-inflammatory effects
- Dramatic effect on numerous processes
- Increase neutrophils
- Decrease lymphocytes, eosinophils, basophils & monocytes
- Inhibit leukocyte migration
Metabolic effects
- Gluconeogenesis so glucose rise
- Lipolysis, Lipogenesis so fat deposition increase
Catabolic effects
- Muscle protein catabolism
- On bone: osteoporosis
- Children: reduced growth
Other effects
- Cortisol needed for natural kidney water excretion
- Glucocorticoid high doses can cause deep behavioral changes
Hydrocortisone
- 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-
Glucocorticoids lengths of effect
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
Beclomethasone, Budesonide, Fluticasone
- 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
Different dosage forms
- Eye drops
- Otic drops
- Ophthalmic ointment
- Lotions
Can use eye for ear / eye and ear drop for skin but NOT the reverse
Clinical uses
1- Adrenal disorders
2- Non-adrenal disorders
Adrenal disorders
1- Addison’s (adrenal insufficiency): Pulse therapy
2- Cushing’s: Non-stop therapy
Non-adrenal disorders
- 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
Toxicity & Side effects
- <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
Minimizing toxicity
- 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
Mineralocorticoids
- Aldosterone
- Fludrocortisone
- Deoxycorticosterone (vet usage)
Aldosterone
- Regulation by ACTH & renin-angiotensin system
- Important for blood volume & pressure
- Short half-life
- Little gluco- activity
Fludrocortisone
- Significant gluco- activity
- 10h gluco-, 125h! mineral-
- Hormone replacement therapy (Cushing’s & Pituitary removal)
Corticosteroid antagonists (inhibitors)
1- Receptor Antagonists:
- Spironolactone
- Eplerenone
- Mifepristone
2- Synthesis Inhibitors:
- Ketoconazole
- Aminoglutethimide
- Metyrapone
- Etomidate
Spironolactone & Eplerenone
- Antagonists of Aldosterone
- Lower blood volume & pressure
- Eplerenone mostly on aldosterone but spironolactone on endrogens too
- In Hirsutism
- Side effects: Hyperkalemia, Gynecomastia (NOT Eplerenone)
Mifepristone (RU-486)
- Progesterone receptor antagonist –> Cushing’s & Abortion
- Glucocorticoid receptor antagonist
Ketoconazole
- 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
Aminoglutethimide
- Blocks cholesterol to pregnenolone conversion
- INDICATION: Steroid-producing adrenocortical cancer
Metyrapone
- Inhibits normal synthesis of Cortisol, NOT the precursors
- INDICATION: Diagnostic tests of adrenal function
Etomidate
- General anesthetic
- Inhibits 11B-Hydroxylase (Corticosterone & Cortisol)
- INDICATION: Cushing’s
Prednisolone
- Activates gluco- receptor
- USES: Inflammatory, organ transplant, Hematologic cancer
- Interactions: Adrenal suppression
