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Flashcards

Steriods

Majd Fawaz Medicinal Chemistry 2 All Inglês 74 flashcards

Steriods

Flashcards do conjunto (74)

  1. 1How is free cholesterol metabolised?- It is converted in the mitochondria via 3-step oxidation to pregnenoloneHow is free cholesterol metabolised?
  2. 2—- Cortisone (inactive)
    - Mineral+Glu corticoid activity
    - Used in adrenocortical deficiency/R.arthritis
    - Short T1/2 (1-1.5hrs)
    - Oral (cortisone acetate) rapid deacetylation
    - IM slow and prolonged release    - Cortisone (inactive) - Mineral+Glu corticoid activity - Used in adrenocortical deficiency/R.arthritis - Short T1/2 (1-1.5hrs) - Oral (c...
  3. 3—- Hydrocortisone
    - Mineral+Glu corticoid activity
    - Used in adrenocortical deficiency/R.arthritis
    - Short T1/2 (1-2hrs)
    - High oral bioavailability
    - Acetyl:Oral/ Butyl-Buteprate-valproate: topical
    - If given oral, completely and rapidly deacetelated    - Hydrocortisone - Mineral+Glu corticoid activity - Used in adrenocortical deficiency/R.arthritis - Short T1/2 (1-2hrs) - High oral bioav...
  4. 4—- Both can be used for IM or IV
    - Succ. is slow&incompletely hydrolyzed and reaches peak levels in 30 mins while the phosphate reaches peak levels in 10 min    - Both can be used for IM or IV - Succ. is slow&incompletely hydrolyzed and reaches peak levels in 30 mins while the phosphate reache...
  5. 5—- Cypionate is insoluble in water, used for slow release in the GI
    - butyl/buteprate/valproate are used topically    - Cypionate is insoluble in water, used for slow release in the GI - butyl/buteprate/valproate are used topically
  6. 6—- Fludrocortisone (acetate)
    - x300-600 MC, x10 GC
    - Used orally in mineral corticoid replacement therapy
    - The glucocorticoid activity is inversely proportional to the size of the halogen    - Fludrocortisone (acetate) - x300-600 MC, x10 GC - Used orally in mineral corticoid replacement therapy - The glucocorticoid activity is...
  7. 7—- Prednisolone
    - 1,2 = x3-4 GC, same MC
    - 80% bioavailability
    - Used for R.arthritis
    - Sodium phosphate: IV or IM fast metabolism and T1/2 5min
    - Tebutate: Used as suspension for IM slow release    - Prednisolone - 1,2 = x3-4 GC, same MC - 80% bioavailability - Used for R.arthritis - Sodium phosphate: IV or IM fast metabolism and T1/...
  8. 8—- Prednisone
    - Prodrug, needs to be converted to prednisolone by 11B-HSD    - Prednisone - Prodrug, needs to be converted to prednisolone by 11B-HSD
  9. 9—
  10. 10—- Methylprednisolone
    - x5 GC, Low MC
    - Intermediate acting
    - 80-90% oral bioavailable
    - Sodium succinate is water soluble so IV    - Methylprednisolone - x5 GC, Low MC - Intermediate acting - 80-90% oral bioavailable - Sodium succinate is water soluble so IV
  11. 11—- Triamcinolone
    - x5 GC, Low MC
    - Intermediate acting
    - 23% bioavailable (OH-->more hydrophilic)
    - Causes sodium excretion and weight loss    - Triamcinolone - x5 GC, Low MC - Intermediate acting - 23% bioavailable (OH-->more hydrophilic) - Causes sodium excretion and weight ...
  12. 12—- Triamcinolone hexacetonide (tebutate)
    - IM prolonged release    - Triamcinolone hexacetonide (tebutate) - IM prolonged release
  13. 13—- Dexamethasone
    - 16-a CH3 stabilizes the 20-keto and increases bioavailability
    - x20-30 GC, lower MC
    - Long acting
    - Increases appetite and weigh gain    - Dexamethasone - 16-a CH3 stabilizes the 20-keto and increases bioavailability - x20-30 GC, lower MC - Long acting - Increases appetite ...
  14. 14—- Betamethasone
    - 16-a CH3 stabilizes the 20-keto and increases bioavailability
    - x20-30 GC, lower MC
    - Long acting
    - Increases appetite and weigh gain    - Betamethasone - 16-a CH3 stabilizes the 20-keto and increases bioavailability - x20-30 GC, lower MC - Long acting - Increases appetite ...
  15. 15—- Beclomethasone (dipropionate)
    - Potent GC (1/2 potency of F analogue)
    - Used as inhalation for asthma and rhinitis
    - Dipropionate is prodrug, monopropionate is active    - Beclomethasone (dipropionate) - Potent GC (1/2 potency of F analogue) - Used as inhalation for asthma and rhinitis - Dipropionate is pr...
  16. 16—- Clobetasol proprionate
    - Used topically
    - Very lipophilic to limit systemic exposure
    - Low bioavailability and high affinity to receptor    - Clobetasol proprionate - Used topically - Very lipophilic to limit systemic exposure - Low bioavailability and high affinity to receptor
  17. 17—- Halobetasol
    - Used topically
    - Very lipophilic to limit systemic exposure
    - Low bioavailability and high affinity to receptor    - Halobetasol - Used topically - Very lipophilic to limit systemic exposure - Low bioavailability and high affinity to receptor
  18. 18—- Mometasone furoate
    - x8 GC of betamethasone 17a- proprionate
    - Very lipophilic
    - Has the greatest affinity for GR receptors
    - Used as inhalation/intranasal for allergic disorders and lung disease
    - Used topically    - Mometasone furoate - x8 GC of betamethasone 17a- proprionate - Very lipophilic - Has the greatest affinity for GR receptors - Used as i...
  19. 19—- Fluticason propionate
    - Very lipophilic
    - Used topically or inhalled
    - Has the second highest affinity to GR receptor    - Fluticason propionate - Very lipophilic - Used topically or inhalled - Has the second highest affinity to GR receptor
  20. 20—- Triamcinolone acetonoid
    - 16,17 sub. enhances lipo --> Increase potency
    - Used inhalation or topically
    - Provides good anti-inflamatory activity    - Triamcinolone acetonoid - 16,17 sub. enhances lipo --> Increase potency - Used inhalation or topically - Provides good anti-inflamat...
  21. 21—- Flunisolide
    - Used inhalation (lung disease) or topically
    - 16,17 sub enhances lipo --> Increase potency
    - Provides good anti-inflamatory activity    - Flunisolide - Used inhalation (lung disease) or topically - 16,17 sub enhances lipo --> Increase potency - Provides good anti-inflam...
  22. 22—- Budesonide
    - No halogen and still active --> Halogen is not necessary
    - Metabolized to 16a-hydroxy prednisolone
    and 6B-budenoside
    - Composed of a mixture of epimers creating a chiral center
    - Inhalation and intranasl for local treatment of lung disease and rhinitis    - Budesonide - No halogen and still active --> Halogen is not necessary - Metabolized to 16a-hydroxy prednisolone and 6B-budenoside - ...
  23. 23What is important for MC ?- Aldosterone
    -All important for MC:
    3-keto
    4,5 =
    18-keto
    21-hydroxy    What is important for MC ?
  24. 24—- Spironolactone
    - Andosterone antagonist
    - Used for hypotensive effect    - Spironolactone - Andosterone antagonist - Used for hypotensive effect
  25. 25Metabolism-Active
    - Inactive    MetabolismMetabolism
  26. 26What are the side effects of glucocorticoids?-Cushing syndrome
    - Stimulates osteoclasts --> Osteoporosis
    - Converting all stored glucose to free glucose --> Hyperglycemia
    - Converting a.a to glucose coupled with not enough a.a intake --> (-) nitrogen balance
  27. 27What is important for GC ?-All important for GC:
    3-keto
    4,5 =
    11-B hydroxy    What is important for GC ?
  28. 28—- 5a androstane
    - Min structure needed for androgenic activity    - 5a androstane - Min structure needed for androgenic activity
  29. 29—- Testosterone
    - 3-keto group enhances androgenic activity
    - 17B-hydroxyl group is also important
    - 17a-hydroxy (epitestosterone) is inactive    - Testosterone - 3-keto group enhances androgenic activity - 17B-hydroxyl group is also important - 17a-hydroxy (epitestosterone) is inac...
  30. 30—- 5a-DHT is the most potent endogenous androgen
    - Estradiol is not active (different activity than the parent compound)    - 5a-DHT is the most potent endogenous androgen - Estradiol is not active (different activity than the parent compound)- 5a-DHT is the most potent endogenous androgen - Estradiol is not active (different activity than the parent compound)
  31. 31What is Hormone Male Contraceptive?- It is based on the delivery of exogenous testosterone alone or with progestin to inhibit the production of endogenous testosterone and spermatogenesis
  32. 32What are the different types of testosterone administration methods?- Injectable: 17B-propionate or Cypionate that lasts 1-4 weeks
    - Transdermal or Gel
    - Bucal
    - Oral is rarely used due to liver toxicity and lower efficiency (17a-methyl testosterone)
  33. 33What are some side effects of TRT?- Begnin prostatic hyperplasia
    - Breast enlargment
    - infertility
    - Growth in muscle mass and strenght
  34. 34—- 17a-methyl testosterone
    - CH3 protects the OH from hepatic metabolism
    - Increases bioavailability
    - Alkylated oral --> Hepatotoxic
    - The bigger the alkyl group --> Less active
    - Has androgenic+anabolic activity    - 17a-methyl testosterone - CH3 protects the OH from hepatic metabolism - Increases bioavailability - Alkylated oral --> Hepatotoxic -...
  35. 35—- Fluoxymestrone
    - Halogen can be tolerated on C4 or C9
    - 11-OH and 9-F were added to 17a-methyltestosterone
    - Still hepatotoxic
    - x10 androgenic, x20 anabolic of testosterone
    - 80% oral bioavailability    - Fluoxymestrone - Halogen can be tolerated on C4 or C9 - 11-OH and 9-F were added to 17a-methyltestosterone - Still hepatotoxic - x10 an...
  36. 36—- Oxymetholone
    - x0.5 androgenic, x3 anabolic of testosterone
    - Orally bioavailable
    - Still hepatotoxic    - Oxymetholone - x0.5 androgenic, x3 anabolic of testosterone - Orally bioavailable - Still hepatotoxic
  37. 37—- Oxymesterone
    - x0.5 androgenic, x3 anabolic of testosterone
    - Orally bioavailable
    - Still hepatotoxic    - Oxymesterone - x0.5 androgenic, x3 anabolic of testosterone - Orally bioavailable - Still hepatotoxic
  38. 38—- Oxandrolone
    - 2-oxasteroid analoge of17a-meth
    - Ring A became a lactone --> could be hydrolized
    - small androgenic activity, x3 anabolic
    - Orally active --> Hepatotoxic    - Oxandrolone - 2-oxasteroid analoge of17a-meth - Ring A became a lactone --> could be hydrolized - small androgenic activity, x3 anab...
  39. 39—- Methenlone
    - C1-C2 = makes the ring more planer --> Greater anabolic activity
    - Alkylation at 1,2,7 increases anabolic activity
    - Oral (acetate) with no hepatotoxicity    - Methenlone - C1-C2 = makes the ring more planer --> Greater anabolic activity - Alkylation at 1,2,7 increases anabolic activity - Or...
  40. 40—- Testolactone (discontinued)
    - Used in the treatment of breast cancer as a noncompetitive irreversible inhibitor of aromatase    - Testolactone (discontinued) - Used in the treatment of breast cancer as a noncompetitive irreversible inhibitor of aromatase
  41. 41—- Boldenone
    - Anabolic with low androgenic activity
    - Used by bodybuilders    - Boldenone - Anabolic with low androgenic activity - Used by bodybuilders
  42. 42—- Nandrolone decanoate
    - Lack of a C-10 reduce androginic and retains anabolic
    !!! Its is the decanoate ester of 19-nortestosterone which is long acting IM injection inteneded to treat anemia in renal insuffiency    - Nandrolone decanoate - Lack of a C-10 reduce androginic and retains anabolic !!! Its is the decanoate ester of 19-nortestosterone which...
  43. 43—- Norethendrolone
    - Lack of a C-10 reduce androginic and retains anabolic
    - Androgenic and progestational side effects
    - Oral    - Norethendrolone - Lack of a C-10 reduce androginic and retains anabolic - Androgenic and progestational side effects - Oral
  44. 44—- Gestrinone
    - Used to treat endometriosis    - Gestrinone - Used to treat endometriosis
  45. 45—- Tetrahydrogestrinone (THG)
    - Illegal anabolic agent
    - Coverting the 17a-alkyne to alkyl increase anabolic activity
    - Was safe and invisible before 2003    - Tetrahydrogestrinone (THG) - Illegal anabolic agent - Coverting the 17a-alkyne to alkyl increase anabolic activity - Was safe and invis...
  46. 46—
  47. 47What are Selective Androgen Receptor Modulaters (SARMs)- Non steriodal androgens
    - Antagonist or weak agonist in androgenic tissue (prostate) to prevent prostate cancer
    - Agonist in anabolic tissue (bone+muscle) used to treat hypogonadism, osteoporosis, and aging related frailty
    - Orally available with low hepatotoxicity
    - Still in the clinical stages
  48. 48What are AR anatgonists?- They are anti-androgens
    - They are given in combination with other drugs to prostate cancer to block Testosteron and DHT from working --> Regressing the tumor
    - Treatment of acne and virilization of women
  49. 49—- Cyproterone acetate
    - Anti-androgen
    - Used to stop excessive hair growth and acne
    - Oxendolone is used as well IM    - Cyproterone acetate - Anti-androgen - Used to stop excessive hair growth and acne - Oxendolone is used as well IM
  50. 50—- Flutamide
    - Oral non-steroidal AR antagonist
    - Its hydroxylated metabolite is more potent and has a higher affinity to the receptor
    - Associated with hepatotoxicity    - Flutamide - Oral non-steroidal AR antagonist - Its hydroxylated metabolite is more potent and has a higher affinity to the receptor - A...
  51. 51What are 5a-Reductase Inhibitors- They inhibit the production of DHT in the prostate --> Reduction is size
    - Given for begnin prostatic hyperplasia
  52. 52—- Fenasteride
    - Selective irreversible inhibitor of type 2 5a-reductase !!!!
    - 2 active metabolites but less active then the parent    - Fenasteride - Selective irreversible inhibitor of type 2 5a-reductase !!!! - 2 active metabolites but less active then the parent
  53. 53—Both are active but less than the parent compoundBoth are active but less than the parent compoundBoth are active but less than the parent compound
  54. 54—- Abiraterone Acetate
    - 17a-hyroxylase + 17,20-lyase IRREVERSIBLE inhibitor
    - Prodrug of abiraterone --> orally active
    - 16,17 double bond essential for activity
    - Inactive metabolites    - Abiraterone Acetate - 17a-hyroxylase + 17,20-lyase IRREVERSIBLE inhibitor - Prodrug of abiraterone --> orally active - 16,17 double ...
  55. 55—- Estradiol
    - The most potent endogenous estrogen
    - Aromatic A ring essentail for activity
    - C-3 + C-17 hydroxyl group are essentail
    - The group between the 2 hydroxyl should be hydrophobic
    - Mainly IV cause orally it sucks
    - Esters of estradiol are IM    - Estradiol - The most potent endogenous estrogen - Aromatic A ring essentail for activity - C-3 + C-17 hydroxyl group are essentail - Th...
  56. 561st Metabolism1st Metabolism1st Metabolism
  57. 57MetabolismMetabolismMetabolism
  58. 58—- Ethinyl Estradiol (EE)
    - Alkylation at C-17 prevents metabolism --> Better bioavailability (40%>)
    - More potent than estradiol
    - Metabolite is 2 hydroxyethinylestradiol    - Ethinyl Estradiol (EE) - Alkylation at C-17 prevents metabolism --> Better bioavailability (40%>) - More potent than estradiol - ...
  59. 59—- Mestranol
    - Prodrug that gives EE upon oral admin.
    - Oral contraceptive    - Mestranol - Prodrug that gives EE upon oral admin. - Oral contraceptive
  60. 60—- Equilenin
    - Estrogen secreted by pregnant mares
    - Used in estrogen replacement therapy
    - The extra double bonds increases the estrogenic potency    - Equilenin - Estrogen secreted by pregnant mares - Used in estrogen replacement therapy - The extra double bonds increases the estrogeni...
  61. 61—- Equilin
    - Estrogen secreted by pregnant mares
    - Used in estrogen replacement therapy
    - The extra double bonds increases the estrogenic potency    - Equilin - Estrogen secreted by pregnant mares - Used in estrogen replacement therapy - The extra double bonds increases the estrogenic ...
  62. 62—- Stillbestrol
    - Nonsteroidal estrogen
    - Derivative of stilbene
    - Potent estrogenic activity
    Note: The distance between the 2 OHs is still the same    - Stillbestrol - Nonsteroidal estrogen - Derivative of stilbene - Potent estrogenic activity Note: The distance between the 2 OHs is stil...
  63. 63—- Genistein (isoflavone)
    - Phytoestrogen
    - Weak estroginic activity
    - Metabolized to give eqoul which has estrogenic activity
    - Used to treat menopause symptoms    - Genistein (isoflavone) - Phytoestrogen - Weak estroginic activity - Metabolized to give eqoul which has estrogenic activity - Used to t...
  64. 64—- Daidzein (isoflavone)
    - Phytoestrogen
    - Weak estroginic activity
    - Metabolized to give eqoul which has estrogenic activity
    - Used to treat menopause symptoms    - Daidzein (isoflavone) - Phytoestrogen - Weak estroginic activity - Metabolized to give eqoul which has estrogenic activity - Used to tr...
  65. 65—- Coumestrol (coumestans)
    - Phytoestrogen
    - Weak estroginic activity
    - Used to treat menopause symptoms    - Coumestrol (coumestans) - Phytoestrogen - Weak estroginic activity - Used to treat menopause symptoms
  66. 66What are the 3 treatment for breats cancer and contraception ?- Impeded estrogen
    - Aromatase Inhibitor
    - Selective Estrogen Receptor Degrader (SERD)
  67. 67- Explain Impeded estrogen- Give estriol in very large amounts to stop estradiol working
  68. 68—- Exemestane
    - Androsteindione derivative type 1 aromatase inhibitor
    - Given oral to compete with androstindione to irreversibly block the conversion to estrogens
    - Treat estrogen dependent and post menopausal breast cancer    - Exemestane - Androsteindione derivative type 1 aromatase inhibitor - Given oral to compete with androstindione to irreversibly block th...
  69. 69—- Anastrazole
    - Triazole derivative type 2 aromatase inhibitor
    - Inhibit the conversion of testosterone to estradiol
    - Bind to the CYP P450 of the aromatase
    - Treat estrogen dependent and post menopausal breast cancer    - Anastrazole - Triazole derivative type 2 aromatase inhibitor - Inhibit the conversion of testosterone to estradiol - Bind to the CYP P4...
  70. 70—- Letrozole
    - Triazole derivative type 2 aromatase inhibitor
    - Inhibit the conversion of testosterone to estradiol
    - Bind to the CYP P450 of the aromatase
    - Treat estrogen dependent and post menopausal breast cancer    - Letrozole - Triazole derivative type 2 aromatase inhibitor - Inhibit the conversion of testosterone to estradiol - Bind to the CYP P450...
  71. 71—- Fulvestrate
    - SERD (antagonist in all tissues)
    - Sub is responsible for the activity, also responsible for poor oral bioavailability
    - IM once a month    - Fulvestrate - SERD (antagonist in all tissues) - Sub is responsible for the activity, also responsible for poor oral bioavailability - ...
  72. 72—- Tamoxifen (prodrug)
    - SERM (structure related to stilbene)
    - Orally antiestrogen in estrogen dependent breast cancer
    - Ether is responsible for activity
    - Can develop resistance
    - 2 active metabolites    - Tamoxifen (prodrug) - SERM (structure related to stilbene) - Orally antiestrogen in estrogen dependent breast cancer - Ether is respons...
  73. 73—- 4-hydroxy tamoxifen
    - Active metabolite    - 4-hydroxy tamoxifen - Active metabolite
  74. 74—- N-desmethy 4-hydroxy tamoxifen
    - Active metabolite    - N-desmethy 4-hydroxy tamoxifen - Active metabolite

Informações

Descrição
All Medicinal Chemistry 2 FlashCards sobre Steriods, criado por Majd Fawaz em 23-05-2021.
Criado por
Majd Fawaz
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