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77 Cards in this Set
- Front
- Back
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What is the classic steroid hormone action?
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- Bind to receptors inside cell
- Alter transcription of DNA - Alter protein synthesis |
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Realistic view of steroidal receptor action?
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Activation depends on coactivators present and may also interact with other transcription factors
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2 types of natural adrenal steroids?
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Glucocorticoid
Mineralocorticoid |
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Cortisol will bind to?
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MR and GR
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Cortisol has higher affinity for?
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Mineralocorticoid receptor
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Which receptor has a higher capacity for cortisol?
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Glucocorticoid receptor have high affinity
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Which enzyme turns Cortisol into Cortisone?
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11BHSD2
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11BHSD2 found in?
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kidney, colon, salivary
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Which enzyme turns cortisone into cortisol?
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11BHSD1
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11BHSD1 found in?
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liver mainly
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Highest potency steroidal compound? lowest potency?
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Highest: Dexamethason/Betamethasone
Lowest:Cortisol |
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Highest dose needed for? lowest dose?
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Highest dose for cortisol
Lowest dose for dexameth |
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Major pharmacologic actions of steroids?
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Anti-inflammatory
Immune suppressive Inhibit tissue degradation |
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Gluco Receptor mediated actions?
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Decrease action of immune system
Inhibit prostanoid production |
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How do gluco receptors decrease action of immune sstem?
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Decrease WBCs
Increase apoptosis of eosinophils and T cells Inhibit IL production |
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Glucocorticoid actions are?
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Decrease IGE stimulated histamine and leukotriene release from mast cells
Decrease macrophage actions Inhibit inflammatory responses in endothelial cells |
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Major effects glucocorticoids?
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Inhibit PG synthesis
Inhibit inflammatory cytokines Inhibit ollagenase |
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Glucocorticoids used to treat?
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Arthritis
Acute regional pain Osteoarthritis Respiratory conditions (asthma, COPD) Allergic Disorderd Dermatologic disorders IBD Acute spinal cord damage Nephrotic disease Antenatal to stim surfactant Specific infectious disease AIDS Autoimmune disease Organ transplant Leukemias Ocular disease |
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Side effects of GC on Adipose? Muscle? Liver?
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Lipolytic enzymes
Protein degradation Gluconeogenic |
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GC is diabetogenic via?
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Protein-wasting
Fat redistribution |
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GC Catabolic effects on Bone? intestine? kidney?
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Inhibit osteoblasts
Inhibit Ca absorption Increases Ca loss in kidney |
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Bone effects?
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Osteoporosis and vertebral compression fractures
Arrested growth in children |
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CV effects of GC?
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Sodium retention = Increase BP
GR may mediate K excretion Thrombosis Dyslipidemia |
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Other side effects of GC?
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Cataracts
Glaucoma Increased infection Poor wound healing (inhibit collagen) Hirsutism |
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Mood effects of GC?
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Initially can cause euphoric
Chronically can cause depression High dose may affect memory |
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How do GC affect endogenous adrenocortical activity?
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Will activate negative feedback and suppress ACTH
Chronic use can reduce size and responsiveness of adrenal gland |
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Major mechanism of estrogens + anti-estrogens?
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Transcriptional activation
Also see some rapid actions via membrane bound receptors |
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Action of the estrogen receptor depends on?
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Ligand binding in order to change a conformation
Activators or repressors binding |
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What types of estrogen receptors?
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alpha and beta
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Differences between ER alpha and beta?
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Similar binding region, similar affinity
Alpha highest in repro tract + CV Beta highest in ovary, prostate |
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Types of progesterone receptors?
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PR-A and PR-B
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PR-A and PR-B do what?
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PR-A does actions
PR-B inhibits actions |
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Key structural feature of estrogen? of progesterone?
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Estrogen = phenolic A ring
Progesterone = 21c steroid backbone |
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Natural estrogens?
Synthetic? |
Natural: estradiol, estrone
Synthetic: diethylstilbestrol, Ethinyl estradiol, mestranol, clomiphene |
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SERMs are? work by?
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Tamoxifen, raloxifene
work by binding in same pocket as estradiol but cause altered conformation |
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Estrogenic formulations?
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Oral - not as good because of high first pass
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How do we deal with high first pass of estradiol?
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ethinyl substitution
conjugated esters |
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Other formulations?
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Patches, IM, Topical, vaginal ring or pellets
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synthetic Progestins
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Pregnanes
Estranes Gonanes |
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Progestin formulations?
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oral - can't be progesterone because high first pass
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How do we avoid the high first pass metab of progestins?
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Esters or 19-nor compounds
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How do 19-nor compounds work?
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Slow hepatic metabolism
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Other formulations
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Micronized
Vaginal gel IUD IM |
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Metabolism of Estrogens/Progestins?
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CYP3A4 hepatically
1A and 1B extrahepatically Excretion in urine Sulfation in liver |
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Therapeutic uses of estrogens/progestins?
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HRT in hypogonadism, oophorectomy
Contraception Cycle normalization HRT post menopausal |
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HRT post menapausal if no hysterectomy?
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Use E and P
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Basis of steroids as contraceptives?
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Estrogen blocks FSH secretion and LH surge by negative feedback effect
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Types of cyclic oral contraceptives?
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Monophasic
Biphasic Triphasic |
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Estrogens in OC?
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Mestranol
Ethinyl estradiol |
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Progestins in OC?
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Norethidrone
Norgestimate Desogestrel Levonorgestrel Drospirenone |
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Positive effects of E+P therapy?
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Reduce incidence of ovarian, endometrial cancer, ovarian cysts, benign fibrocystic breast disease
Decrease LDL increase HDL |
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Negative effects of therapy?
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breast tenderness, edema, HA, anorexia, N
Increase risk of HTN, thrombosis, Gall stones CI in women who smoke, TE disease |
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Drugs that can affect Estrogen affects?
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Phenytoin
Barbituates Carbamazepine Antibiotics |
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Drugs that Estrogen will affect?
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Cyclosporine
Glucocorticoids Imipramine Warfarin |
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Types of Progestin only OC?
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Minipills
Plan B IM IUDs |
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What is in minipills?
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Norethidrone
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What progestin is in Plan B
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Levonorgestrel
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What progestin is in IM?
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MPA
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What progestin is in IUD?
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Progesterone
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Advantage of Progestin only?
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women who smoke
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Disadvantage of progestin only OC?
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Irregular menses
Less effective |
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MOA of progestin only OC?
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Blunt LH surge
Increase thickness of cervical mucus to impeded sperm |
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Anti-progestins?
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Mifepristone
Ulipristal |
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Most common HRT in the US?
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Premarin
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All HRT have risk of?
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thrombosus
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Positive effects of HRT?
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Diminish Sx of menopause:
- hot flashes, vaginitis Reduce incidence of colon cancer or osteoporosis |
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Combination HRT decrease risk of? increase risk of?
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Decrease risk of: Osteoporosis, colorectal cancer
Increase risk of: MI, Stroke, DVT, PE, Dementia |
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Estrogen only HRT decrease risk of? Increase risk of? no change on?
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Decrease risk of: Hip fractures
Increase risk of: Stroke, DVT no effect on breast cancer or MI |
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SERMs are?
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tissue selective
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3 major problems in Tamoxifen?
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Drug resistance in 5 yrs
Action on endometrium - increase Cancer Increase risk of TE |
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Selective antagonist
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Clomiphene - antagonist at most places including CNS
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Pure Antagonist or estrogen receptor downregulator
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Fulvestrant
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Fulvestrant used in?
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Tx of advanced breast cancer in postmenopausal women
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Aromatase inhibition works by?
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Blocking conversion of androgens to estrogens
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Steroidal aromatase inhibition?
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Formestane
Exemestane |
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Non-steroidal aromatase inhibition?
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Anastrozole, letrozole
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Aromatase inhibitors used to tx?
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Tamoxifen resistance breast tumors
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