31263811
Description
Flashcards by Majd Fawaz, updated more than 1 year ago
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Created by Majd Fawaz
about 3 years ago
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| Question | Answer |
| How is free cholesterol metabolised? | - It is converted in the mitochondria via 3-step oxidation to pregnenolone |
| - 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 | |
| - 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 | |
| - 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 | |
| - Cypionate is insoluble in water, used for slow release in the GI - butyl/buteprate/valproate are used topically | |
| - 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 | |
| - 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 | |
| - Prednisone - Prodrug, needs to be converted to prednisolone by 11B-HSD | |
| - Methylprednisolone - x5 GC, Low MC - Intermediate acting - 80-90% oral bioavailable - Sodium succinate is water soluble so IV | |
| - Triamcinolone - x5 GC, Low MC - Intermediate acting - 23% bioavailable (OH-->more hydrophilic) - Causes sodium excretion and weight loss | |
| - Triamcinolone hexacetonide (tebutate) - IM prolonged release | |
| - Dexamethasone - 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 and weigh gain | |
| - Beclomethasone (dipropionate) - Potent GC (1/2 potency of F analogue) - Used as inhalation for asthma and rhinitis - Dipropionate is prodrug, monopropionate is active | |
| - Clobetasol proprionate - 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 | |
| - 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 | |
| - Fluticason propionate - Very lipophilic - Used topically or inhalled - Has the second highest affinity to GR receptor | |
| - Triamcinolone acetonoid - 16,17 sub. enhances lipo --> Increase potency - Used inhalation or topically - Provides good anti-inflamatory activity | |
| - Flunisolide - Used inhalation (lung disease) or topically - 16,17 sub enhances lipo --> Increase potency - Provides good anti-inflamatory activity | |
| - 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 | |
| What is important for MC ? | - Aldosterone -All important for MC: 3-keto 4,5 = 18-keto 21-hydroxy |
| - Spironolactone - Andosterone antagonist - Used for hypotensive effect | |
| Metabolism | -Active - Inactive |
| What 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 |
| What is important for GC ? | -All important for GC: 3-keto 4,5 = 11-B hydroxy |
| - 5a androstane - Min structure needed for androgenic activity | |
| - Testosterone - 3-keto group enhances androgenic activity - 17B-hydroxyl group is also important - 17a-hydroxy (epitestosterone) is inactive | |
| - 5a-DHT is the most potent endogenous androgen - Estradiol is not active (different activity than the parent compound) | |
| What 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 |
| What 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) |
| What are some side effects of TRT? | - Begnin prostatic hyperplasia - Breast enlargment - infertility - Growth in muscle mass and strenght |
| - 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 | |
| - 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 | |
| - Oxymetholone - x0.5 androgenic, x3 anabolic of testosterone - Orally bioavailable - Still hepatotoxic | |
| - Oxymesterone - x0.5 androgenic, x3 anabolic of testosterone - Orally bioavailable - Still hepatotoxic | |
| - Oxandrolone - 2-oxasteroid analoge of17a-meth - Ring A became a lactone --> could be hydrolized - small androgenic activity, x3 anabolic - Orally active --> Hepatotoxic | |
| - Methenlone - C1-C2 = makes the ring more planer --> Greater anabolic activity - Alkylation at 1,2,7 increases anabolic activity - Oral (acetate) with no hepatotoxicity | |
| - Testolactone (discontinued) - Used in the treatment of breast cancer as a noncompetitive irreversible inhibitor of aromatase | |
| - Boldenone - Anabolic with low androgenic activity - Used by bodybuilders | |
| - 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 | |
| - Norethendrolone - Lack of a C-10 reduce androginic and retains anabolic - Androgenic and progestational side effects - Oral | |
| - Gestrinone - Used to treat endometriosis | |
| - Tetrahydrogestrinone (THG) - Illegal anabolic agent - Coverting the 17a-alkyne to alkyl increase anabolic activity - Was safe and invisible before 2003 | |
| What 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 |
| What 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 |
| - Cyproterone acetate - Anti-androgen - Used to stop excessive hair growth and acne - Oxendolone is used as well IM | |
| - Flutamide - Oral non-steroidal AR antagonist - Its hydroxylated metabolite is more potent and has a higher affinity to the receptor - Associated with hepatotoxicity | |
| What are 5a-Reductase Inhibitors | - They inhibit the production of DHT in the prostate --> Reduction is size - Given for begnin prostatic hyperplasia |
| - Fenasteride - Selective irreversible inhibitor of type 2 5a-reductase !!!! - 2 active metabolites but less active then the parent | |
| Both are active but less than the parent compound | |
| - Abiraterone Acetate - 17a-hyroxylase + 17,20-lyase IRREVERSIBLE inhibitor - Prodrug of abiraterone --> orally active - 16,17 double bond essential for activity - Inactive metabolites | |
| - 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 | |
| 1st Metabolism | |
| Metabolism | |
| - Ethinyl Estradiol (EE) - Alkylation at C-17 prevents metabolism --> Better bioavailability (40%>) - More potent than estradiol - Metabolite is 2 hydroxyethinylestradiol | |
| - Mestranol - Prodrug that gives EE upon oral admin. - Oral contraceptive | |
| - Equilenin - 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 potency | |
| - Stillbestrol - Nonsteroidal estrogen - Derivative of stilbene - Potent estrogenic activity Note: The distance between the 2 OHs is still the same | |
| - Genistein (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 treat menopause symptoms | |
| - Coumestrol (coumestans) - Phytoestrogen - Weak estroginic activity - Used to treat menopause symptoms | |
| What are the 3 treatment for breats cancer and contraception ? | - Impeded estrogen - Aromatase Inhibitor - Selective Estrogen Receptor Degrader (SERD) |
| - Explain Impeded estrogen | - Give estriol in very large amounts to stop estradiol working |
| - 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 | |
| - 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 | |
| - 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 | |
| - Fulvestrate - SERD (antagonist in all tissues) - Sub is responsible for the activity, also responsible for poor oral bioavailability - IM once a month | |
| - 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 | |
| - 4-hydroxy tamoxifen - Active metabolite | |
| - N-desmethy 4-hydroxy tamoxifen - Active metabolite |
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