March 22, 2007

March 22, 2007 This section is on the Test for Tuesday Drugs Affecting the Endocrine System (Part 1)  Basically how everything works in the body  Includes all the organs involved in secreting hormones  Horomes travel through blood and have effects on target tissues  Have no ducts  Main endocrine organs o Pituitary o Pineal o Thyroid o Parathyroid o Adrenals o Ovaries o Testes  Impt are sex and thyroid hormones  Book: Naturopathic Endocrinology (CCNM Press) Friedman, Michael  Endocrine o Add Raloxifene after Tamoxifen on the ‘HORMONES’ list  Antierior Pituitiary o GH  Stimulates cells growth for most cells in body o ACTCH  Stimulates cortisol (stress, effects metabolism of CHO, protein and fat)  Aldosterol - Responsible for water and electrolyte balance  When released BP goes up b/c water being retain and Na going up o FSH  Promotes growth of follicle in ovaries and sperm formation in men o Prolactin  Encourages breast development  Posterior Pituitary o ADH  Acts as KI and blood vessel having KI retain water and increase BP  Pineal o Melatonin  Target in the brain itself and the Immune system  Brief summary of target sites  Primary action in body is concerned to be the governing of sleep and wake cycle  Main ND use: in treatment of CA and hormone irregularities (esp. unopposed estrogen)  Melatonin in CA

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Increases tumor cell apoptosis Reduces cacexia symptoms in late HIV/AIDS Improves survival time as a sole agent in terminal CA patients Certain quality of life that comes with that 1st patient – elderly woman having 4th episode of Breast CA. Had 15 to 20 mg of melatonin per night. She lasted a year and a half Always take only at night (at bedtime)

 Thyroid Gland o T3 and T4 promote certain chemical reactions in the cell o They force a particular hormone balance in the body o When inducing a specific hormonal state, very hard to get body to control after o Calcitonin  Promotes the depositing of Ca into the bone  Parathyroid Glands o Increases Ca in the blood o Parathyroid hormone  A lot of depression out there being misdiagnosed, and person is put on SSRI, and antidepressants when actually have a problem in parathyroid hormones  Can have a benign tumor on a parathyroid hormone that is secreting too much hormone causing depression symptoms  Adrenal Medulla  Adrenal Cortex o Aldosterone  Acts at the KI or sweat glands to promote water and sodium o DHEA  Actions at Immune system and brain  Precursor to androgen hormones  Promotes mood  DHEA o Secreted in greater quantity than any other adrenal cortex hormone o Circulating levels of DHEA decrease with age (one of the only ones) o Associated with longetivity (so if going down and put back, you live longer) o Considered an anti-aging hormone o Important in viral immunity o Increases natural killer cell immunity o Prevents thymus involution as quickly as it may otherwise o Improves mood balance, especially when compared to cortisol o Melatonin improves the secretion of DHEA

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o Supplementation is safe but longtime chronic use not studied o Macca – balancer of hormones  acts as an adaptogen at the level of the hormones  raises those that are too low and lowers those that are too high  adrenal adaptogen in menopause  approx 1000 to 3000mg/day  safe to use long-term Pancreas o Insulin and Glucogon play important role in influencing adrenal glands o High CHO diet causes high Insulin release causing high amounts of glucosamines (not safe in IDDM or NIDDM), results in insulin resistance o Insulin there but not working o Receptors on the cell turn off when there are too many of these sugar coated proteins o Followed by a spike in cortisol levels o If insulin no longer works, can’t get in at all o Sugar needed in cell to maintain metabolismthink that the body is in stress and end up releasing cortisol o Will go on to develop NIDDM o Has to do with insulin and adrenal glands, cortisol, etc. Ovaries Testes o Have production of testosterone – anabolic steroid o Synthesized from cholesterol o In response to the signal provided by LH released from ant. Pitu – released in a daily rhythm o Peak in AM and go down in PM o As men age, testosterone levels decline to almost 50% by age 50 o Levels of testosterone linked to CVD in men o Angina, increased incidence of MI  linked to high amount of estrogen in men o High levels of testosterone in women detrimental effects in women o High levels of testosterone in men  protective Gonadal Hormones and Inhibitors o Hormones themselves being used as agents and then synthetic o Estrogen  Estrone = ci • Synthesized in ovaries o Progesterone  Synthetic forms  Progesterone itself is produced in ovaries and adrenal cortex o Testosterone  Involved in

Low testosterone in women – osteioperosis, decreased Lean body mass,  Elevated Testosterone in women – PCOS, insulin resistance  Anti-Estrogens • Primary function by competing with estrogen and bind at estrogen receptors but don’t get estrogen effect • Tamoxifen o Agonist- activates receptor o Antagonist- - blocks intended reaction o Is a partial agonist – got estrogen agonists effects in vagina and endometrius (high incidence of endometrial CA) o Estrogen antagonistic effect in breast o Roloxafine is very similar o Clomiphene • Given to women who are preparing for artifical insemination • Promotes the production of FSH • More ovulation happening • Greater chance of pregnancy o Hormone Precursors  Androstenedione • Intermediate in the production of Esterone and Testosterone  Pregnenolone • 150 steroid hormones all derived from Pregnenolone  DHEA o Birth Control  Drospirenone • BC agent but works differently • Speronal lactone analogue progestin– diuretic • Spironolactoestrogen Acts like speronal lactone with anticorticomineral or anti-aldosterone activity • Can increase K levels by blocking aldosterone  Medroxyprogesterone • Injectible synthetic progesterone • Every 3 mo • Prevents ovulation • If give supplemental progesterone  prevent ovulation • But as a side effect, contributes to bone loss b/c of decreased serum estrogen • b/c of this the use of this drug is not recommended for longer than two years 

Norgestinmate – oral form of estrogen, found together with ethanol estradiol • Take every day  Norelgestromin – patch form of estrogen • 7 day patch • Combined with ethanol estradiol • All three are synthetic progesterone o Drospirenone  Newer BC agent  Estrogens are known to increase levels of aldosterone  Also causes increase in other mineralcorticoid hormones  Manifests with slight rise in BP and Na and water retention  b/c this drug is a spironolactonediol – blocks aldosterone  not holding onto Na and water and K sticks around. Symptoms like water retention, bloating are less likely to occur  should not be used in women with severe renal disease b/c of blocking of aldosterone, hepatic dysfunction, or especially in women with a predisposition of hyperkalemia  can end up with too much potassium and end up with problems in the heart 2-OH Estrone – good estrogen 16-OH is bad Estradiol o Strongest o 12 times as potent as E1 o Estriol is inverse relationship with Breast CA E3/sum of (E1+E2) o Quotient develops relative risk of Breast CA o Not used anymore o Now use 2-hydroxy E1/16 Hydroxy E1 Average values of this ratio are between 2 and 2.3 The higher the value the more protection you have If it’s 2-OH E1 then the whole number is higher The higher the amount of 2OH E1 the less likely chance of getting Breast CA Men and women who consume larger amounts of Brassica family foods drecrease chance of Breast CA and Prostate CA Conjugated Estrogens Anti-Estrogens o Clomiphene  Estrogen receptor agonist in CNS and GU  Promotes the intended action of estrogen  Used as a fertility drug in woman with low FSH 

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Induces ovulation by increasing LH which increases amount of FSH and therefore ovulation  Implicated in a condition called ovarian hyperstimulation syndrome • Can end up with too much stimulation • Can result in ovarian enlargement, hepatic dysfunction (b/c drug that’s cleared through system), and severe systemic dysfunction and death resulting from hypovolemic shock • Visual spots and blurring  Doesn’t interact with other drugs  Drug cleared through LIV so can potentially increased the amount of other drugs  No known drug interactions per se  Considered relatively saf  Go to www.rxlist.com • Get mechanism of action, and all other info o Tomoxifen  Used in Breast CA prevention  Estrogen agonist in the endometrium bone and lipids  The agonist part of tomoxifen is a good thing, b/c it promotes Ca staying in bone  Less risk of osteoporosis  LDL and HDL are positively influenced  Used in estrogen receptor positive breast CA  Understand where it is an agonist and antagonist  Too much Ca in the blood when there is metastasis to the bone. Increased risk of hypercalcemia  Agonists in the endometrium  increased risk of endometrial/uterine CA  b/c estrogen agonist in certain tissues  there’s an increased risk of deep vein thrombosis and other thromoboenvolic events in the body (eg. LU embolisms)  hepatic dysfunction  end up with increased AST and increases risk of LIV cancer  melatonin and black cohosh helps Tamoxifen works better  use quercetin which is better than Tomoxifen o Raloxifene  Works like Tomoxifen but used specifically for the effect of preventing bone loss  Move to use it instead of Tomoxifen in postmenopausal bone loss and breast CA treatment  Increases bone mineral density  Decrease in total and LDL cholesterol  No effects on good cholesterol (HDL) 

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Estrogen antagonist in uterine tissue No effects on triglycerides

 Melatonin o Got info form book: Naturopathic Endocrinology o Cortisol released by adrenal glands are cyclic (highest at AM and lowest at PM) o Melatonin is opposite o We live chronically stressful lifestyles o In chronic stress, cortisol never comes down or is too high too often (at day and night) o Melatonin used for adrenal fatigue, b/c pushes cortisol levels down o Deficiency  Too much Estrogen  Deficiency o Excess  Thyroid implication  The Male Hormone o Testosterone  Hypergonadism can be d/t aging, congenital, surgery (testicular CA, accident), chemotherapy, Kleinfelter’s, tobacco smoke, alchol and cannabis use  All decrease functioning of sperm  Nutrients that improve testosterone production and production of other hormones and thus sperm • Vit. C, E, Zn, argentine, EFA  Preferred method is prescribed transdermally  Bioavailability is reduced  More toxic than when begin with (speed up stage one but not stage 20 )  end up with more toxicity in the body  Orally may cause increased first pass effect and increase chance of LIV CA  DHEA is sometimes given as a precursor to increase testosterone  The Thyroid Gland o Reverse T3 – hormonally active keeps T3 in check  Produced from T4 as well  At target site either T4 works itself, or T3 or reverse T3 created  Thyroid Hormone Synthesis o Not on test  Thyroid Facts o Made mostly at target tissue site, mainly at level of LIV and KD where T3 is made o T3 and T4 have exact same function, but T3 is much stronger o Function is to increase oxygen in all tissues and thus increase metabolism o Hashimotos’ is most common type of hypothyrodism

See high TSH b/c HYPO thyroidism – not enough T3 and T4 produced  Ant. Pit hormone is constantly being thrown out to produce horomone, but none made  T4 is most commonly produced, is relatively normal o A lot of drugs interfere with thyroid  Lithium – long-term  Oral hypoglycemic agents (some of the drugs used in diabetes)  Amyolerone (?) – arrhythmia  Tricyclic antidepressants o Other drugs will alter the peripheral confersion of T3/T4  Will be producing T3  Dexamethazone  Peripheral conversion of T4 to T3 in the tissues  Propanolol  High Soy diets • Alter T3 to T4 conversion • Could theoretically lead to hypothyroidism  Unopposed estrogen • Impairs ability of T3 and T4 • Functionally/clinically hypothyroidism in menopause b/c of unopposed estrogen  Thyroid Hormones o Hypothyroidism  Levothyroxine • m/c’ly used drugs to treat hypothyroidism • synthetic T4 • a lot of drugs interfere with it  Liothyronine • Can get hypo to hyper very fast with this drug b/c absorbed really well in GI • Thyroid storm • Might use synthetic T3 if synthetic T4 didn’t work • Also may be used as a last resort if T4 and dessicated allergies  Dessicated Thyroid • Glandular form of natural ratios of thyroid o Any hypothyroid medication should be used carefully in people history or current CVD o Look at Rxlist.com  Inhibitors to Thyroid Hormone Synthesis o Antagonists that block thyroid peroxidase o Presently two types of drugs, thioureylenes 

 Thyroid Hormones o Hyperthyroidism  Put people on these drugs just long enough to bring levels of thyroid down then go into surgery where they kill the thyroid and render you hypothyroidism state for life o Don’t put a hyperthyroid person on drug for too long o