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139 Cards in this Set
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Activates iodide |
TPO |
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An intermediate on the way to a highly reactive species of iodide |
Iodine |
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Adds I to thyroglobulin via organification |
TPO |
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Will couple diiodotyrsoine residues to monotyrosines to make T3 and T4 |
TPO |
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This enzyme works in peripheral tissues to make T3 from T4 |
5'-Diodinase |
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Used for replacement therapy to give back the hormones that are no longer being produced, must be careful as to not produce symptoms of hyper or hypo thyroidism |
Thyroid drugs |
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- Most popular drug for replacement therapy in hypothyroidism because they can produce T3 from this so the patient ends up with a lot of T3 and T4. |
Levothyroxine (pure T4) |
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Levothyroxine (thyroxine, tetraiodthyronine) half life |
~7 days |
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- Has to be given several times a day, effective orally |
Liothyronine (T3) |
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Usually used in emergency situations and you need to get thyroid hormone in quickly because T3 is 4-5x quicker in its ability to bind thyroid receptor and T3 is also more potent |
Liothyronine (T3) |
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Liothyronine (T3, Triiodothyronine half life) |
~24 hours |
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Tries to mimic normal natural mixture of a euthyroid person, not seen to have an advantage over giving T4 on it's own |
Liotrix (T4 +T3 in a 4:1 ratio) |
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Discouraged because |
Thyroid hormones from pigs |
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Will inhibit the enzyme thyroid peroxidase, thus will inhibit iodination and coupling in the thyroid. |
Propylthiouracil and Methimazole |
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Inhibit peripheral conversion from T4 to T3 |
PTU |
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Clinical response to these drugs is usually observed after 3-4 weeks of therapy |
Thioamides: PTU and Meth |
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PTU half life and how many times given a day? |
- 1 hr |
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Methimazole half life and how many times given a day? |
- 7 hr |
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Potential adverse side effects |
Thioamides, mainly PTU |
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- Corticosteroid |
Dexamethasone |
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- Quickly inhibits T3 and T4 secretion (unknown mechanism) also transiently inhibits TPO |
Iodide (at high doses), lugol's (5% iodine, 10% potassium iodide) solution and potassium iodide |
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- Blocks increased sympathetic activity in hyperthyroidism mediated by beta blockers |
Propranolol |
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- Used because T3 and T4 help regulate the # of adrenergic receptors in various locations throughout the body. |
Propranolol |
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- Can be taken orally as sodium iodide for thyroid ablation - Beta emitter - kills cells in the thyroid, patients can become hypothyroid, but it is easer to treat hypo than hyper so it is worth the risk |
Radioactive iodine (131I) |
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Radioactive iodine (131I) half life |
~ 8 days |
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Very fast acting drugs because they via protein phosphorylation in the cell |
Peptide drugs |
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Not available after oral administration, so they need to be administered in other ways because they become degraded in the stomach |
Peptide drugs |
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Hormones of the pituitary as drugs |
Not used |
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Hormones of the pituitary as drugs |
Not used as drugs, but used diagnostically |
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Uses - Growth hormone deficiency |
Clinical uses of GH |
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- Idiopathic short stature - Anti-aging hormone (unsubstantiated) |
Controversial uses of GH, GRH, Somatostatin (GHIH) |
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Drugs used to suppress GH levels, or inhibit GH activity in acromegaly |
- Somatostain analogs |
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Somatostatin analogs half life |
3 minutes |
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Octreotide half life and how often you give |
Give subcutaneous every 8 hour, 1.5 half life |
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- Effective in 50-75% of patients |
- Somatostatin analogs |
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- Inhibits release of CCK |
- Somatostatin analogs |
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- Overall effective in 1/3 patients |
Dopaminergic agonists - Cabergoline |
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- Can be used in combo with somatostatin analogs or alone |
Competitive antagonists of GH - Pegvisomant (Give SC 1x/day because it is a peptide) |
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Side effects include abnormal LFTs and hypoglycemia |
Competitive antagonists of GH - pegvisomant |
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Will see elevated FSH and LH in first few days of treatment and will see elevated estrogen in the blood because LH stimulates elevated production of estrogen |
GnRH effects |
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- Stays bound to the receptor much longer than GnRH |
Leuprolide |
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- Used for its FSH activity |
Human menopausal gonadotropin (HMG) |
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- Agonist of LH |
Human Chorionic Gonadotropin (HCG) |
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- Synthetic GnRH |
Gonadorelin |
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- Long acting GnRH agonist |
Leuprolide |
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Condition in pre-menopausal women where a piece of the endometrium ends up in the peritoneal cavity. |
Endometriosis |
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Vasopressin half life |
20 min |
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Desmopressin half life |
2 hr |
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Acts on V1 and V2 (ADH) |
Vasopressin |
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Only at V2 |
Desmopressin |
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Will cause constriction to help decrease hemorrhaging. (The SST analogs are used for bleeding esophageal varices-especially octreotide.) |
Vasopressin causing bleeding esophageal varices |
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Which receptor is responsible for vasoconstriction? |
V1 |
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Which receptor is responsible for reabsorption of water by the kidney? |
V2 |
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Will cause release of VW factor and factor VIII so can only give it to mild forms of these diseases because they need some of the factor to release |
Treat with IV desmopressin |
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Why can desmopressin by given orally despite it being a peptide? |
Only 0.1% is absorbed, but that is all you need |
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In control of ATII, a little bit in control of ACTH |
Aldosterone |
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Mostly controls ACTH and a little bit of ATII |
Cortisol |
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Can have CV effects because adrenergic receptors (B1, B2, A1) |
Glucocorticoids |
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- It was discovered because of its effect on the immune system and inflammation |
Cortisol |
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Inhibitor of phospholipase A2, which will block production of PGE and leukotrienes |
Lipocortin (annexin A-1) stimulated by Cortisol |
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Stimulate synthesis of lipocortin (Annexin A-1) |
cortisol |
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Inhibit synthesis of NF-Kb (nuclear factor kappa-light-chain-enhancer of activated B cells) |
Cortisol |
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Induce tdag8 (T-cell death associated gene 8) in lymph tissue |
Cortisol |
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This receptor can be activated by a number of things (including a slight change of pH) but when it is activated it leads to apoptosis of lymph tissue |
tdag8 |
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What does inhibit synthesis of NF-kB and activator protein-1 do? |
Pro-inflammatory cytokines |
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Result of altered Gene expression, which step? |
Step 1 |
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Result of altered Gene expression, which step? |
Step 2 |
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Result of altered Gene expression, which step? |
Step 3 |
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Result of altered Gene expression, which step? |
Step 4 |
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Result of altered Gene expression, which step? |
Step 5 |
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IgE ABs bind to receptors on mast cells causes release of what? |
Histamine |
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Stabilize mast cell membranes (also happens in basophils) so will stop the release of histamine. |
Cortisol and cortisol-like agonists |
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Giving back cortisol that is not there, replacement therapy for that? |
Addison's disease |
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This is for a long treatment by chronic condition, wouldn't use glucocorticoids in acute settings |
Severe allergic reactions |
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Glucocorticoids used to suppress immune system for this |
Autoimmune diseases |
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OTC topical application. Oral glucocorticoids only by Rx. Some are so lipid soluble they can get across skin |
Skin diseases |
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To trigger apoptosis of cancer cells and some to suppress nausea and vomiting only in chemotherapy (not motion sickness) |
Oncology - lymphoma and acute lymphocytic leukemia, nausea and vomiting |
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Chronic inflammatory disease, suppresses the chronic inflammation, can be taken via inhalation or orally or injected |
Bronchial asthma |
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About 10% of babies born less than 34 weeks gestation (premature). Biggest problem is lack of surfactant in lungs, give glucocorticoids to the mom 48 hrs and 24 hrs before delivery |
Fetal lung maturation |
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Side effects and toxicities of glucocorticoids: |
Increase susceptibility to infections |
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Side effects and toxicities of glucocorticoids: |
Osteoprosis |
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Side effects and toxicities of glucocorticoids: |
Peptic ulcers |
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Side effects and toxicities of glucocorticoids: |
Cataracts, glaucoma |
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Side effects and toxicities of glucocorticoids: |
Slow wound healing |
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Side effects and toxicities of glucocorticoids: because cortisol is telling muscle to break down protein, to release amino acid's to be converted to glucose |
Muscle wasting |
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Side effects and toxicities of glucocorticoids: |
Behavioral disturbances |
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Hydrocortisone duration of action |
8-12 hrs |
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Prednisone duration of action |
18-36 hrs |
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Betamethasone, dexamethasone duration of action |
1-3 days |
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Drug for fetal lung maturation |
Betamethasone |
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Can be used in emergency hyperthyroidism to stop peripheral conversion of thyroid hormone |
Dexamethasone |
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Stimulates the release of ACTH and ACTH stimulates the release of what? |
Vasopressin and cortisol |
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Competitive inhibitor of aldosterone at the MR receptor |
Spironolactone |
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- Inhibits CYP17 |
Ketoconazole |
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Like cortisol, this hormone will increase or decrease transcription of certain genes in certain tissues |
Estrogens |
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Causes negative feedback on the hypothalamus to stop producing estradiol, exert feedback inhibition on the hypothalamus thus causing decreasing GnRH = lower FSH, LH |
Estradiol or a drug that is an agonist of estradiol |
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Increase in GnRH, FSH, LH and increase synthesis of estradiol |
Estradiol antagonist |
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Prototype, responsible for most of actions of estrogen in the body because it is more potent at the estrogen receptor |
Estradiol |
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- Required for normal maturation |
Estrogen |
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When is it okay to give unopposed estrogen? |
Women w/o uterus |
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Stabilizes endometrium |
Progesterone |
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Estradiol levels go up as you approach this |
Ovulation stage |
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When is estrogen replacement therapy indicated? |
Women who are in a high risk category for osteoporosis |
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Premenopausal replacement therapy such as premature ovarian failure |
- Estrogen |
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Can treat endometriosis because it exerts negative feedback inhibition to dial down levels of estradiol |
oral contraceptives |
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Used to to treat PCS |
Oral contraceptives |
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The estrogen and progesterone in oral contraceptives work to inhibit feedback at the hypothalamus, why do you still have to give estradiol and progesterone? |
Because the hormones in OCs do not do the normal job on estradiol and progesterone |
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- Metabolites of the natural estrogens |
Conjugated estrogens - estradiol sulfate |
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- Made an ester at the 17c position of estradiol |
Esterified estrogens - estradiol valerate |
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- Converted to ethanol estradiol by removing the methyl group and leaving an OH |
Mestranol |
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- Nausea |
OC ADR |
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Mothers who are taking estrogens as a drug who are pregnant with a female fetus, that female fetus has an increased risk for what? |
Vaginal adenocarcinoma |
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Two major pathways for ethinyl estradiol to be broken down? |
- P450 |
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If ethinyl estradiol is broken down by P450, what does it become? |
2-hydroxy ethinyl estradiol |
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If ethinyl estradiol is broken down by glucuronyl transferases, what does it become? |
Ethinyl estradiol glucuronide |
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If taking these drugs, oral contraceptives need to be broken down differently as they compete for P450 activity |
Griseofulvin, Rifampin |
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- Developed to protect against osteoporosis, but has similar effects as tamoxifen for estrogen-dependent breast cancer. |
Raloxifine |
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- For osteoporsis (agonist for osteoblasts) |
Bazedoxifene |
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- Used to lower rate of recurrent estrogen dependent breast cancer |
Tamoxifen in estrogen dependent breast cancer |
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- Cause some increased proliferation of the endometrium and after 5 years, the risk benefit analysis goes upside down for endometrial cancer |
Tamoxifen in endometrium |
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Acts as antagonist on receptors of hypothalamus blocks feedback inhibition of estradiol, opposite of oral contraceptives, tricks hypothalamus that is not enough estradiol and endogenous estradiol increases |
Clomiphene |
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- Binds to ER (in estrogen dependent BC cells) but keeps the receptor as a monomer (unlike tamoxifen, which forms a dimer) and the complex stays in the cytosol and does not go into the nucleus so it gets broken down |
SERDS (Selective estrogen receptor downregulators) - fulvestrant |
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Sources of estrogen |
Premenopausal |
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Sources of estrogen - Breast |
Postmenopausal |
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- Only used in post-menopausal women because their source of estrogen is mainly extra-gonadal production, if given in premenopausal women, hypothalamus will turn out very large amounts of GnRH which will make lots of FSH and LH |
Aromatase inhibitors (CYP19A1, estrogen synthetase) |
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Inhibits these reactions Testosterone -> estradiol |
Letrozole, aromatase inhibitors |
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- Render endometrium inappropriate to implantation and production of mucus at the cervix |
Progestins |
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The main ingredient in plan B |
Levonorgestrel |
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Progestins - Anti-estrogenic only |
Progesterone |
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Progestins - Androgenic |
Medroxy-progesterone |
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Progestins |
Megestrol |
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- Chemical abortion - Antagonist to progesterone |
Antiprogestins - mifepristone |
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- Required for normal maturation |
Androgens |
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- Replacement therapy |
Indications for Androgens |
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Wasting syndrome sometimes in terminal cancer or AIDs patients |
Cachexia |
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- Masculinization in women |
Androgens - ADR |
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If you are taking anabolic steroids, what can you take to counter the decreased spermatogenesis? |
Human menopausal gondadotropin |
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Inhibits 5a-reductase enzyme. Testosterone is converted to DHT to bind to the Androgen Receptor and this drug will inhibit that |
Anti-androgens: finasteride |
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Will block binding DHT to the androgen receptor. approved to treat prostate cancer |
Anti-androgens: flutamide |