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Therapeutics 6
N/A
55
Pharmacology
Graduate
10/22/2011

Additional Pharmacology Flashcards

 


 

Cards

Term
Functions of Adrenocorticoids
Definition
  • Carbohydrate biosynthesis (activates glycogen synthesis)
  • Lipid biosynthesis
  • Protein Biosynthesis:inhibits activity
  • Immune function: supresses it
  • Cellgrowth/death: supresses growth, promotes apoptosis
Term

Therapeutic goal of Adrenocorticosteroids

 

Definition
Optimize gulcocorticoid activity, while concurrently minimizing mineralocorticoid activity
Term
[image]
Definition
  1. C3 has a keto side chain
  2. C4,5 are double bonded
  3. C11 has a beta (inactive)keto or (active)hydroxy group
  4. C 17 has a beta ketol side chain
  5. C21 has a terminal OH
  6. C17 has a alpha hydroxy group
Term
Modifications for Adrenocorticosteroids
Definition
  1. C 21: Modifications create prodrugs. Hydrophilic groups have rapid activity, hydrophobic groups are long lasting. C21 Chlorine potentiates activity.
  2. C 9alpha: Adding an ectron withdrawing group increase glucocorticoid activity x10 and mineralocorticoid activity x300-800x. If C16 group is added it blocks mineralocorticoid activity.
  3. C 1,2: Double bond increases glucocorticoid activity.
  4. C 6alpha side chain blocks catabolism.
  5. C 16 side chain. Supresses mineralocorticoid activity. Also can block C 17 catabolism.
Term
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Definition
Prednisone
Term
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Definition

Methylprednisolone

 

C6 alpha side chain. Causes blocking of catabolism

Term
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Definition

Triamcinolone(Adrenocorticosteroid)

 

C16 addition leads to low mineralocorticoid activity.

C9 modification increases receptor activity. 

 

Term
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Definition

Triamcinolone acetonide(Adrenocorticosteroid)

 

  • C 16 side chain is lipophilic. Lead to low mineralocorticoid activity.
  • C 9 modification increases Receptor activity.
Term
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Definition

Dexamethasone(Adrenocorticosteroid)

 

  • Catabolically blocked: prevents C 17 attack
  • Greater activity per dose amount than prednisolone, but about equal usefulness in therapy
Term
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Definition

Betamethasone(Adrenocorticosteroid):

 

  • Catabolically blocked: prevents C 17 attack
  • Greater activity per dose amount than prednisolone, but about equal usefulness in therapy
Term
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Definition

Paramethasone (Adrenocorticosteroid):

 

  • Catabolically blocked: prevents C 17 attack
  • Greater activity per dose amount than prednisolone, but about equal usefulness in therapy
Term
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Definition

Fluandrenolone (Adrenocorticosteroid):

 

Topical

Term
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Definition

Flucinolone (Adrenocorticosteroid):

 

Topical

Term
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Definition

Fluorometholone (Adrenocorticosteroid):

 

Topical

Term
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Definition

Fluprednisolone (Adrenocorticosteroid):

 

Topical

Term
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Definition

Halcinonide (Adrenocorticosteroids):

 

  1. Highly active topical ACS
  2. C21 Chlorine potentiates activity
Term
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Definition

Clobetasol/Halobetasol proprionate (Adrenocorticosteroid)

 

  • Highly Active topical Adrenocorticosteroids
  • C21 Chlorine potentiates activity
Term
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Definition

Fluticasone proprionate/FlonaseR (Inhaled ACS):

 

  • C16aCh3 increase lipophilicity.
  • High receptor activity.
  • Very high systemic metabolism
  • C16 blocks catabolism
Term
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Definition

Beclomethasone diproprionate (Inhaled ACS):

 

  • Prodrug
  • Lipophilic
  • C16 blocks catabolism
Term
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Definition

Mometasone Furoate/Nasonex (Inhaled ACS):

 

  • Lipophilic
  • C16 blocks catabolism and increases lipophilicity.
Term
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Definition

Estrone (Estrogen):

 

E2> estrone > Estratriol

Term
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Definition

17-Beta Estradiol

 

E2> Estrone> Estriol

Term
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Definition

Estriol (Estrogen):

 

An antagonist

Term
Therapeutic goals of estrogens
Definition
  • Therapeutic goal 1: Develop a very easily administered form for contraception. i.e. an orally active form.
  • Develop a form that is atheroprotective & and cognition and bone preserving without causing Cancer.
  • Blocking catabolism will prolong lifetime and make estrogens orally active.
Term
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Definition

Estrogens

 

  • C3 has a -OH side chain
  • C17 has a beta -OH side chain
  • A ring is fouly double bonded
  • Does not require a steroid nucleus. It is critical that the OH groups are seperated by the right distance.
Term
[image]
Definition

Ethinyl Estradiol (Synthetic Estrogens)

 

  • Blocks catabolism of C17alpha ethinyl
Term
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Definition

Estradiol Valerate/Natazia(Estradiolvalerate and dienogest)

 

  • Increase active lifetime by creating prodrugs with either C3 or C17 or both (Hydroxyls are derivatized)
Term
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Definition

Dienogest (Synthetic estrogens)

 

Increase active lifetime by creating prodrugs with either C3 or C17 or both (Hydroxyls are derivatized)

Term
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Definition
Equilin (Estrogens for postmenopause hormone replacement)
Term
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Definition

Stilbene (Estrogenic Compounds lacking a steroid nucleus)

 

  • High activity without an intact nucleus
  • Highly active
Term
[image]
Definition

Diensetrol (Estrogenic Compound lacking the steroid nucleus)

 

  • High activity without an intact nucleus
  • Highly active
Term
[image]
Definition

Hexestrol (Estrogenic Compound lacking the steroid nucleus)

 

  • High activity without an intact nucleus
  • Highly active
Term
[image]
Definition

Benzestrol (Estrogenic Compound lacking the steroid Nucleus)

 

  • High activity without an intact nucleus
  • Highly active
Term
[image]
Definition

Chlorotrianese (Estrogenic compounds lacking steroid nucleus)

 

  • Long lived in body slowly released
Term
[image]
Definition

Genistein (Xenoestrogens)

 

Isofavenoid with weak estrogen activity

Term
Types of antiestrogens
Definition
  • Impeded Estrogens: Compete for binding, bind weakly and do not activate (Estriol)
  • Triphenylethylenes: Bind strongly but do not activate
  • Aromatase inhibitors: Block conversion of androgen precursors into estrogens.
Term
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Definition
Tamoxifen (Anti estrogens-Triphenylethylenes)
Term
[image]
Definition
Raloxifene (Antiestrogens- Triphenylethylenes)
Term
[image]
Definition

Aromasin/ Exemestane

 

Antiestrogens: Aromatase inhibitors

Prodrug

Irreversible suicide inhibitor

Metabolized by cyp 3A4

 

Term
Therapeutic Goals of Progesterones
Definition
  • The main therapeutic use is for contraception
  • Develop a very easily administered form for contraception i.e. orally-active form
  • Steroid nucleus structures in the estrane, androstane, and pregnane class all can activate the progesterone receptor
Term
Structual Modifications of Progesterones
Definition
  1. C 17 alpha blockade avoids catabolism.
  2. C 6 side groups help blocking catabolism.
  3. Removal of the C 19 methyl increases activity.
  4. C17 Beta configuration is required for activity.
Androstane based Progestins
  • Two C17alpha side chain provide activation of the progesterone receptor and block catabolism. 
  • Can also have C 6 catabolism blockade.
  • Moving 4,5 double bound to 5,10 decreases activity.
  • Adding a C 18 molecule increases receptor binding. "Gonanes"
Term
[image]
Definition

Progesterones

 

  1. Requires an intact nucleus and the 4-5 double bond
  2. Not required: C20-21 promote binding.
  3. Forms lacking C3 keto can still be active prodrugs.
  4. Does not require a C19 side chain.
Term
[image]
Definition

17 alpha blocked progesterones (Progesterones)

 

  • OR blocks catabolism of the required C17beta side chain. Acetate has a weak oral activity. The caproate has a stronger oral activity.
Term
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Definition

Medroxyprogesterone Acetate (Catabolically blocked Progesterones)

 

  1. Blocked in C 17 and in C 6 position
Term
[image]
Definition

Megestrol acetate ( Catabolically blocked progesterones)

 

  • Blocked at C 17 position and at the C 6 position.
Term
[image]
Definition

Chlormatidone acetate (Catabolically blocked Progesterones)

 

  • Blocked at C 6 and C 17 position
Term
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Definition

Demethyl Progestins

 

  • Removal of C 19 methyl increases activity. 
  • C 17 beta configuration required for activity.
Term
[image]
Definition

Demethyl progestins

 

  • Removal of C 19 methyl increases activity.
  • C 17 beta configuration required
Term
[image]
Definition

4th Generation demethyl progestins

 

  • High activity at the progesterone receptor (C 19 removal)
  • Low activity at other steroid Receptor
Term
[image]
Definition

Androstane Based Progestins

 

  • Two Carbons in the C 17 alpha side chain block catabolism. And provide activation of progesterone receptor.
  • Dimethisterone contains a second catablolic blocking group at the C6.
Term
[image]
Definition

Androstane demethyl progestins

 

  • C 17 double C activate progesterone receptors and catabolically block the compound. 
  • C 19 demethyl increases activity
Term
[image]
Definition

Demethyl Androstane Progestins

 

  • Gonanes
  • Adding an additional C 18 increases receptor binding.
  • Desogestril and Norgestimate have decreased androgenic side effects
Term
[image]
Definition
  • C3 keto is not required
  • C 17 has a beta OH side chain
  • 4,5 double bond is inhibitory.
  • Many modifications are tolerated
  • Can remove C 19 methyl group to make nor form with higher anabolic activity
Term
Structual Modifications of Androgens
Definition
  • C 17 catabolic blockade creates orally active form
  • C 17 acetoxy makes it a prodrug.
  • Increased activity when C19 is removed.
  • C 2 keto is dispensible.
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