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
 • 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
 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
  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)
  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