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The Steroids are a group of substances of ______________origin.
both plant and animal
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All steroids possess what characteristics?
 - Tetracyclic backbone/skeleton derived from cyclopentanohydrophenathrene
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Among the steroids are substances of very considerable medicinal importance such as:
- Adrenocortical hormones
- sex hormones
- vitamin D2
- cardiac glycosides
- sterols
- bile acids.
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________________may be considered the starting point with some of it synthesized in the cortex from acetate.
Cholesterol
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Some cholesterol used in steroid synthesis in the adrenal cortex is derived endogenously from what?
Acetate
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__________________ probably represents the major source of cholesterol for the biosynthesis of the various steroids.
Exogenous dietary cholesterol
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Corticosteroids are classified into two groups, what are they?
- Adrenocorticoid hormones
- Sex hormone
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What are the Adrenocorticoid hormones?
- Glucocorticoids
- Mineralcorticoids
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Describe the Hypothalamic/pituitary control of Glucocorticoids:
- Hypothalamus: CRF (corticotrophin releasing factor)
- Pituitary: ACTH (adrenocorticotropic hormone)
- Adrenal cortex: Synthesizes and releases GC
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What is the general action of GCs in the peripheral tissues?
- Production of glucose from non-sugar sources
- Inhibit the use of glucose in the tissues
- Promote gluconeogenesis
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Describe the physiological control of Mineralcorticoids:
- Octapeptide angiotensin II
- Stimulates synthesis of permease called: antiduiretic-induced protein (AIP)
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What is the general action of MCs in the peripheral tissues?
- REtation of Na
- K and H excretion
- Maintain blood volume
- Electrolyte regulation
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What group of patients should MCs be avoided in?
HTN
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What group of patients requires supplementation of MCs?
Addison’s
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Describe how Glucocorticoids and mineralocorticoids act on the receptor/cell?
- Pass through cell membranes into the cytosol and bind to intracellular receptor proteins
- Form a steroid-receptor complex
- Translocation to nucleus
- Initiates transcription
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The portion of MC or GC receptors that binds to _____ is highly conserved, and looks the same regardless of receptor type.
DNA
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The domain that binds the ________ is different from one type of steroid to the next.
Steroid
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GC receptors are believed to interact with which face of the glucocorticoid structure?
Beta
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MC receptors are believed to interact with which face of the mineralocorticoid structure?
Alpha
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What general effects are Corticosteroids used for?
Glucocorticoid effects
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____________ activity of corticosteroids is considered undesirable therapeutically.
Mineralcorticoid activity
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What are the general therapeutic uses of Corticosteroids?
- Anti-inflammatory agents
- Immunosuppressants
- Anti-allergic acitivty
- Replacement therapy
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How do GCs have Anti-inflammatory activity?
- GCs stimulate the synthesis of Lipocortin, which inhibits phospholipase A2
- PLA2 cleaves AA from Phospholipids resulting in inflammatory prostaglandins
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What diseases are treated by the anti-inflammatory effects of GCs?
- Rheumatoid arthritis
- Bursitis
- Contact dermatitis
- Autoimmune disease
- Ulcerative colitis
- Enteritis
- Erythema
- Exfoliative dermatitis
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How do GCs inhibit the immune system?
- Inhibit Interleukin-1 (IL-1)
- Impacts proliferation of B-lymphocytes
- Inhibits activation of T-lymphocytes
- Decreased IL-2 production
- TNF is decreased
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In what group of patients should Immunosuppressant GCs be avoided in?
Those with an infection
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How do GCs prevent allergic activity?
Inhibit synthesis and release of histamines
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Why do GCs need weaning during D/C?
Hypothalamic-Pituitary-Adrenal axis suppression occurs with use
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Under what conditions do you not need to wean patients off of Glucocorticoids?
Short treatments of 7-10 days
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What are the side effects of GC therapies?
- Increased infection risk
- Increased BP
- Salt/water retention
- Increased K secretion
- Increased Ca excretion
- Muscle weakness
- Osteoporosis
- Peptic ulcer
- Cushingoid state
- Decreased growth
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Describe the basic skeleton structure which steroid hormones are derived from:
- Perhydro (saturated)
- Tetracyclic (four rings, three cyclohexane and one cyclopentane)
- Called cyclopentanoperhydrophenanthrene
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What is the most stable conformation, chair or boat, of cyclopentanoperhydrophenanthrene?
Chair
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What is a sterol?
- Cyclopentanoperhydrophenanthrene w/ hydroxyl groups
- (Cyclopentanoperhydrophenanthrene shown)
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What is a sterid?
- Cyclopentanoperhydrophenanthrene basic hydrocarbon structure
- (Cyclopentanoperhydrophenanthrene shown)
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What is a Steroid?
- Cyclopentanoperhydrophenanthrene w/ more carbonyl groups
- (Cyclopentanoperhydrophenanthrene shown)
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All steroids have one or two angular methyl groups at what locations?
 - C13 and or C10
- Numbered: C18 (at C13) and C19 (at C10)
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Some steroids have an additional carbon chain attached at what point?
 - 17 Beta
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Under what conditions can a steroid have a two carbon chain at 17 Beta?
- Must have C13 and C10 methyls
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What are the two carbons attached at 17 Beta named?
- C20 and C21
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 Which is the A ring?
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Which is the B ring?
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Which is the C ring?
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Which is the D ring?
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In the corticoids and sex steroids, the A/B ring fusion and the C/D ring fusion are most commonly ______________, making the entire steroid structure very flat.
 - Trans
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What is the allo conformation of a steroid?
- A/B is trans (C/D is also trans)
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What is the “Normal” conformation of the steroid?
 - A/B is cis (C/D is still trans)
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