ENDOCRINE PHARMACOLOGY (PART 5)

Gonadal Hormones
➔ AKA Sex Hormones or reproductive hormones
◆ Synthesize by the gonads or the reproductive organs that are necessary for the:
● conception
● embryonic maturation
● development of primary and
● secondary sexual characteristics at puberty
➔ NOTE:
◆ Sex hormones are sytnthseize at the adrenal cortex
◆ They are steroidal hormones that are actually derived from cholesterol
◆ Gonadal hormones are therapeutically used replacement therapy for
contraceptives
● Can also be used for menopausal symptoms

● Estradiol: Estrogens
● Progestins: Progestogens
● Androgens: Testosterone

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 I. Estrogens
● synthesized from cholesterol, secreted by the ovaries and placenta
● Endogenous estrogen
○ Estradiol (17β-estradiol)- most potent, pre-menopausal hormone
○ Estrone-estradiol metabolite, 1/3 estrogenic potency, post- menopausal
hormone
■ Primary circulating estrogen after menopause
● Typically higher after menopause
■ Weakest type of estrogen
○ Estriol-less potent than estradiol, principal estrogen produced by the placenta
■ Present in significant amount in pregnancy
● Explanation:It is present during pregnancy since it is the
principal estrogen produced by the placenta
● Chemically modified to a metabolic steroid (?)
Synthetic Estrogens
● Ethynyl estradiol, Mestranol, Diethylstilbestrol
○ They undergo LESS first pass metabolism compared to the natural steroids in
the body and thus are effective when administered orally at lower doses
● Oral, transdermal, IM, implantable, topical
○ Wide range of route of administration available
● Single agents or combined with progesterone
Mechanism of Action of Estrogen
● Binding to type 4 nuclear receptors such as ERα and ERβ
○ Specific receptors for estrogen
○ 2 types of Estrogen receptors
■ Estrogen Receptor Alpha
■ Estrogen Receptor Beta
● Binding causes genomic effects
● steroid-receptor complex with nuclear chromatin for hormone- specific RNA synthesis
● Results: synthesis of specific proteins
NOTE: When steroid hormones diffuse across the cell membrane, they bind with the high
affinity to the specific nuclear receptors. As with other steroids, Estrogen binds to type 4
nuclear receptors (2 types of Estrogen receptors: ERα and ERβ) then after binding, it is
followed by the interaction of the resultant complexes, this complexes with nuclear site and
subsequent genomic effect (genomic effect: includes the activated steroid receptor complex
interacting with the nuclear chromatin {chromatin: combination of DNA and proteins), this
complex will initiate the synthesis of RNA for specific hormones and this result into the
synthesis of specific proteins (or production of proteins) that will mediate physiological
function of steroidal hormones
Vascular outcomes
● initiating second- messenger cascade
● dilation of coronary arteries
● release of nitric oxide and prostacyclin
○ involves the vascular action because of the production of nitric oxide and
prostacyclin wherein they are potent vasodilators
NOTE:
● Some estrogen effects in particular are rapid vascular action and this could be
initiated by the interaction of the other membrane receptor
● Other pathway that requires these hormones have been identified that could lead to
rapid or quick action
● E.g: Activation of estrogen receptor in the membranes of hypothalamic cells that
have been shown to coupleG protein, if there is a GP then there will be an initiation
of the secondary messenger cascade → if there is a secondary messenger
cascade → then there would be an estrogen mediated dilation of coronary arteries
due to the formation and release of nitric oxide and endothelial cells
Therapeutic Applications of Estrogen
● Replacement Hormone Therapy for Hypogonadism, Ovarian Failure in Turner’s
syndrome and Menopause (premature or surgical)
○ Estrogen deficiency could be caused by many reasons such as:
■ Hypogonadism: Inadequate functioning of the ovaries
■ Ovarian Failure in Turner’s syndrome
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 ■ Menopause (premature or surgical) ● Estrogen can work overtime in our body, the estrogen
● Premature: happens when a woman’s period stop before the therapy keeps the estrogen levels up which protects against
age of 45, normally menopause occurs during the ages of 45 bone thinning and help prevent menopause symptoms
to 50
● Surgical: Happens after oophorectomy (surgical removal of
ovaries) since wala na magsusupply ng estrogen. Unwanted Effects of Estrogen
● Tenderness in the breasts, nausea, vomiting, anorexia, retention of salt and water
○ Contraception for sexually mature women (with progesterone) ⬆
with edema, and increased risk of thromboembolism
■ Amount of estrogen used for contraception is substantially more than
○ Note: has mineralocorticoid action which has retention of salt and water
the doses used in replacement therapy
○ Mild anabolic action (from simple → complex)
● Mas madami ang dose ng estrogen if it is being used as a
○ Increase plasma concentration high density lipoprotein which is beneficial since it
contraceptives. Thus, the adverse effect of estrogen for
contributes to having low risk of atherosclerosis since the HDL increase therefore
contraceptive purposes are more pronounce kapag it is used
there is a decrease in the buildup of fats, cholesterol or other substances in the
for contraception than those seen from women taking
wall of the arteries
estrogen for hormonal replacement
■ Men of the same age as women in menopausal (45 - 55 above has a
○ Induction of artificial for primary amenorrhea (with progesterone)
higher risk of atherosclerosis for men compared to women
■ Primary Amenorrhea: abnormal absence of menstruation
○ Estrogen also increases the coagulability of the blood which increase
● Estrogen given recurrently or for specific period of time and
thromboembolism and this effect is dose related, this is why we want to reduce
continuously, (normally for progesterone) this would
the systemic effect of estrogens.
eventually induce the artificial cycle
● menstruation-like bleeding, endometrial hyperplasia, feminization when
● Postmenopausal Hormone Therapy
administered in male
○ for menopausal symptoms: vasomotor instability and vaginal atrophy
○ Estrogen helps the body to improve the lining of the uterus
■ vasomotor instability: hot flashes in vasodilation due to prostacyclin
○ Feminization: opposite of virilization; stimulate the development of secondary
and nitric oxide
sexual characteristic of women
■ Vaginal atrophy: condition where the lining of the vagina gets drier and
■ Virilization: due to excessive testosterone
thinner due to the lack of estrogen
○ NOTE: unwanted effect of estrogen could affect BP and Cardiovascular system
● Patient would feel burning sensation, itching, spotting, pain in
due to thromboembolism and water retention however it is still beneficial due to
the reproductive organ, frequent urination and prone to UTI
increase HDL (lowers the risk of atherosclerosis)
● Estrogen targets the vagina rather than the systemic
estrogen
Selective Estrogen Modulators
■ Note: If there is Urogenital symptoms (vaginal atrophy), we would like ● Class of estrogen-related compounds that display selective agonism or antagonism for
to reduce the systemic effect of estrogen estrogen receptors
● Should be treated with vaginal estrogen rather than systemic ● Raloxifene: selective estrogen receptor modulator (SERM)
estrogen to reduce systemic effect ○ ❌anti-estrogenic on breast and uterus
○ for women with intact uterus: (with progesterone) reduces the risk of ■ Anti estrogenic effect on the breast reduce the incidence of estrogen
endometrial carcinoma associated with unopposed estrogen therapy receptors positive breast cancer and uterus
○ for women who had hysterectomy: unopposed estrogen therapy ● Some tumors takes up a lot of estrogen
■ Hysterectomy: surgical removal of ALL or some parts of the uterus ■ They have antagonist effects and agonist effects → known as
■ Unopposed estrogen therapy: aka estrogen dominance modulators because they can have both of these
● Increase in concentration of the estrogen → without the
progesterone balancing influence
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 ■ Breast and uterus: Reduced the incidence of receptor breast cancer
and uterus → it would not contribute to breast cancer and uterine
cancel
○ ✅estrogenic on lipid metabolism , bone and blood coagulation treatment of
post-menopausal osteoporosis
■ Lipid metabolism: Lowers the total cholesterol and lowers LDL, but
with high HDL
■ Estrogenic effect on the bone: It promotes bones resorption which
retains calcium channel and improves bone density which will
decrease the fracture
■ Raloxifene: Used for osteoporosis and post menopausal symptoms.
○ Treatment of post-menopausal osteoporosis
● Tamoxifen: selective estrogen receptor modulator (SERM)
○ anti estrogenic action on mammary tissue
■ Used for estrogen dependent breast cancer
■ Beneficial especially to those that have breast cancer
○ estrogenic actions on plasma lipids, endometrium and bone
■ Mild estrogen like adverse effect are consistent with the Partial agonist
activity
Tamoxifen and Raloxifene have no estrogenic effect in endometrium.
Take note: Tamoxifen together with raloxifene they do not have appreciable estrogen receptor
agonist activity in the endometrium → it will not predispose the patient into endometrial cancer →
because if there are estrogenic effect in the breast and uterus then most probably the agent will
cause tumors and cancer because having tumor secretes a lot of hormones.
● Clomephene/Clomefene
○ acts as a partial estrogen agonist and interferes with the negative feedback of
estrogens on the hypothalamus
■ Interferes with the negative feedback of estrogen on the hypothalamus,
this interfering would eventually INCREASE the secretion GNRH and
the gonadotropin
● If there is an increase in gonadotropin, there will be an
ovulation since the gonadotropins would release the FHS
and LH → used mainly for ovulation
○ For Infertility due to anovulation
■ Used for female infertility
■ Anovulation: Experience for patient with PCOS → it happens when
the egg (the ovum) is not release from the ovary, so nag stay lang siya
sa ovary, hindi siya mag dedevelop sa follicle and corpus lithium and
hindi din sya made fertilize → there would be no ovulation and there
would be a problem in the menstrual cycle
■ Negative feedback of estrogens on the hypothalamus → increased the
secretion of the Gonadal Releasing Hormone ( GNRH) and
Gonadotrophines (release fsh and lh) → there would be an ovulation
■ Bad things of clomifene can lead to multiple ovulation → there would
be a conceiving of twins, triplets, or even multiple pregnancy, but still
effective for female infertility.
○ stimulate the release of gonadotropins, follicle-stimulating hormone (FSH), and
luteinizing hormone (LH)
II. Progestogens
● Progesterone: natural progestogen
○ produced in response to LH by both females and males
○ synthesized by the adrenal cortex in both sexes
○ Main hormone in the natural progestogen: Progesterone [MAIN HORMONE] →
secreted by the corpus lithium in the female ovaries and placenta during ovaries
■ Small amount secreted in the testis and adrenal cortex
● Progestins: synthetic progestogen
○ Progesterone by itself is not widely used as a contraceptive therapy because of
its rapid metabolism → it has very poor or low bioavailability
■ The solution: make it in synthetic form (Progestins)
○ Progestins: They are more stable to first pass metabolism allowing lower doses
that could be administer orally and some could be in combination with estrogen
in different routes of administration
○ Synthetic form: Desogetrel, Dienogest, Drospirenone, Levonorgestrel,
Norethindrone, Norethindrone acetate, Norgestimate, and Norgestrel,
Medroxyprogesterone
● Note:
○ Progestin
■ In normal dose: for pregnancy
■ In high doses with testosterone: Contraceptives
Therapeutic Applications of Progestogens
● For contraception: used in combination with estrogens
● control of dysfunctional uterine bleeding, treatment of dysmenorrhea, and management of
endometriosis and infertility
○ Dysmenorrhea because of hormonal imbalance
○ Related to gonadotropins hormones and HCG
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● Medroxyprogesterone acetate: injectable contraceptive, and the oral form is a common ■ Have different doses and it could also be one type of hormone/
progestin component of postmenopausal HT combination
■ Not only orally administered but could also others
Unwanted Effects of Progestogens ○ 21 or 22 days per cycle
● weak androgenic actions ○ Contraceptives has a lot of route of administration
● acne, fluid retention, weight change ● Most common estrogen in combination pills: ethinyl estradiol
● depression, change in libido ○ The ethinyl estradiol (estrogen) will combined with progestins
○ Libido: Lessen the androgenic actions ● Most common progestins: norethindrone, norethindrone acetate, levonorgestrel,
● breast discomfort, irregular menstrual cycles desogestrel, norgestimate, drospirenone
● risk of thromboembolism Combination of Contraceptives
Antiprogestins ● Monophasic pills: same amount & proportion
● Mifepristone: progesterone antagonist with partial agonist activity ○ Mono meaning one phase pills → the pocket contains the same amount of
○ Anti → Inhibit progesterone from eliciting their biological effects to the body hormones and in the same proportions
● sensitization of uterus to prostaglandin ● Biphasic and Triphasic pills: different doses and proportions of hormones
○ During the pregnancy: It sensitizing the myometrium (wall of the uterus) to the ○ take 21-22 days
action of prostaglandin ■ They should be in correct order (21-22 days) to work properly
■ Prostaglandin: induce uterine contraction ○ 6- or 7-day break during which the monthly period occurs
● Uterine contraction is something that they make used of for ■ May break kapag may menstruation
certain purposes clinically but as to the route of ■ Question: Paano yung 6-7 days break, pwede kayang mabuntis during
administration if mifepristone is given orally it has plasma menstruations?
half life of 21 hours ● ANS: Pregnancy will STILL PREVENTED during these
● in combination with prostaglandin breaks
○ Gemeprost: used for preoperative dilation of the cervix ● In the Philippines, we have 28 pills per pocket but during the
■ It is a medical alternative to surgical termination of pregnancy 6-7 day break, yung laman ng pills are not hormones/ drugs
therefore if gemeprost is given to women especially to pregnant but rather ferrous sulfate.
women in the first trimester it could induce uterine contraction and
could terminate pregnancy. Action of Contraceptives
○ facilitating therapeutic termination of pregnancy in patients in the second ● prevent fertilized eggs from implanting into the womb
trimester of gestation ○ Increased supply by contraceptive → have higher doses of the hormones →
■ It should be used judiciously with monitoring and further consultation estrogen and progestins will provide a negative feedback → kasi nga masyado
with physician ng mataas yung mga hormones (Hormones: FSH and LH)
III. Contraceptives ■ Kapag konti yung FSH and LH → It will prevent ovulation
● Birth control, also known as contraception, is the use of medicines, devices, or surgery to ■ Hormones and contraceptive DO NOT ONLY PREVENT OVULATION
prevent pregnancy. but it could work in many ways, aside from being the egg be fertilized
○ Combinations of hormones especially estrogen and progesterone in the synthetic in the uterus
form ○ SUMMARY: There is increase in the supply of hormones by contraceptive →
● Hormonal Methods higher doses of estrogen and progesterone → negative feedback in the release
○ combined pills of LH and FSH → low LH and FSH → prevent ovulation

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● cause the mucus in the cervix (the opening of the womb) to become thick and sticky,
making it harder for the sperm to move and reach the egg cell
○ Contraceptives not only prevent ovulation, they also cause mucus in the cervix,
which will make it hard for the sperm cell to move to the egg cell.
■ Mahihirapan na makapasok yung sperms becuase of the thick and
sticky mucus
● Contraceptives may have Reduced in effectiveness when used with antibiotics,
blood-pressure-lowering or cholesterol- lowering drugs, antifungal drugs or herbal products
like St. John’s wort.
○ When using contraceptives, know if the patient is taking these medications
because it may hinder the effectiveness of contraceptives.
Alternative to Oral Contraceptives
● Transdermal patch: Ethinyl estradiol + Norelgestromin→ applied each week for 3 weeks
to the abdomen, upper torso, or buttock
○ Has good efficacy comparable to oral contraception
○ Drawback: it is less effective for women weighing greater than 90 kg. (Not
recommended with women with this weight)
● Vaginal ring: Ethinyl estradiol + Etonogestrel; ring is inserted into the vagina and is left in
place for 3 weeks then removed
○ Drawback: It may cause nausea, irritability and depression (fewer), risk to
vaginal infection (vaginitis)
Alternative to Other Contraceptives
● Progestin-only pills: Norethindrone (called “mini-pill”)
○ may produce irregular menstrual cycles
○ for px who are breast-feeding, intolerant to estrogen, smokers and have
contraindications to estrogen-containing products
○ Taken orally daily on continuous schedule in low doses
○ Contains fewer progestin
○ Drawback: Less effective than combination product and may cause irregular
menstruation more frequently than combi product
○ Adv: Can be used by patients with problem with estrogen; by breast feeding
patients (they cannot take medicine with estrogen for it can affect milk
production, so progestin is recommended)
● Injectable progestin: Medroxyprogesterone acetate
○ weight gain, amenorrhea with use in women; IM or SQ
○ delayed return to fertility
○ Adv: More convenient because administered every three months
○ Drawback: weight gain, ammonrehea, and return to fertility may be delayed for
several months after discontinuation
■ may contribute to bone loss and cause osteoporosis
○ Drugs should not be continued for more than 2 years due to its side effects such
as osteoporosis and fracture.
● Progestin implants: Etonogestrel; offers contraception for approximately 3 years
○ Implant → Subdermal placement
○ Very reliable as sterilazaiton
○ Its effect is reversible basta inalis na sya surgically
● Progestin intrauterine device: Levonorgestrel; offers effective method of contraception
for 3-5 years
○ Very suitable to women who desire long term contraception
○ Should be avoided by patients with pelvic inflammatory disease or who have a
history of ectopic pregnancy.
● Postcoital contraception: high doses of Levonorgestrel or high dose of Ethinyl estradiol +
levonorgestrel→ taken as soon as within 72 hours of unprotected intercourse
○ It is termed as Emergency Contraception
○ Reduces probability of pregancy after an episode of sexial intercourse without
effective contraception
IV. Androgens
● Testosterone: most important and natural androgen in humans synthesized by the Leydig
or interstitial cells in the testes and in smaller amounts by thecal cells in the ovaries and by
the adrenal glands in both sexes.
○ The adrenal androgen production is controlled by the ACTH hormones and
even the corticotropins.
● Other androgens secreted by the testes: 5α- dihydrotestosterone (DHT),
androstenedione, dehydroepiandrosterone (DHEA)
○ DHEA: precursor of testosterone and estrogen
● Applications: used for males with primary hypogonadism or secondary hypogonadism
○ Hypogonadism: testes does not produce testosterone that much
■ Secondary: caused by failure of the hypothalamus or the pituitary gland
● Anabolic steroids: androgens modified chemically (it can be synthetically made) to alter
the balance of anabolic and other effects
○ Anabolic → increased protein synthesis → Muscle development
○ AE: aplastic anemia, cholestatic jaundice, liver tumors and increased risk of
coronary heart disease (benefits don't outweigh risks)
■ Nandrolone: increase bone density and muscle mass in patients with
osteoporosis
Anti- Androgens
Estrogen and Progesterone → has anti androgenic activity
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● Estrogen inhibits gonadotropin (LH and FSH) secretion and progestogens by competing at
androgen receptors in target organs
● Cyproterone is a derivative of progesterone and has weak progestational activity
○ Suppress action and release of testosterone and other other metabolism (DHT,
DHEA) → prevent androgen from binding to the receptors → suppress LH →
no testosterone secretion.
○ for palliative treatment in prostatic carcinoma
■ Used for males with hypersexuality in the form of prostatic carcinoma
○ in combination with estrogen: for severe acne and hirsutism (excessive hair
growth) of females.
● Flutamide: non-steroidal antiandrogen used with GnRH in the treatment of prostate cancer
○ inhibitor of testosterone-stimulated prostatic DNA synthesis
○ Note: Prostate cancer is androgen sensitive → so it will respond to treatments
that counteracts androgen Bone Disorders
● Finasteride: inhibits the enzyme (5α-reductase) that converts testosterone to ● Hyperparathyroidism
dihydrotestosterone (DHT) ○ PTH excess characterized by hypercalcemia, bone pain, cognitive abnormalities,
○ Oral treatment of BPH (Benign Prostatic Hyperplasia) ○
■ DHT is primary androgen, has important role in development and ○
enlargement of prostate gland → no DHT → no enlargement of ○ and renal stones
prostate gland → no BPH ■ Increase in PTH, and any hyperactivity of it effects calciums
■ Used as an hormonal mediator for hyperplasia so there would be no ○ Can be primary and secondary
increase in size of prostate gland ■ Primary: affects the actual gland
■ Secondary: result of chronic kidney disease (which normally retain
calcium and will be reabsorbed → hypercalcemia)
ENDOCRINE PHARMACOLOGY (PART 6) ● Forms a lot of crystallization that would lead to
hyperthyroidism
Mineral Homeostasis ● Calcium → Crystallization → Renal stones
● Mechanical Bone Strength: Calcium and Phosphorous ● Osteomalacia
○ Others: magnesium, manganese, fluoride and Vitamin A ○ abnormal mineralization of adult bone secondary to nutritional deficiency of
■ Not significantly in control vitamin D or inherited defects in the formation or action of active vitamin D
○ Primary regulators: Parathyroid hormone (PTH) and vitamin D metabolites
■ They try to balance calcium and phosphorus after excretion ■ For older people
○ Secondary regulators: calcitonin, glucocorticoids, and Estrogens ■ Problem when activating vitamin D
■ Assist primary regulators to attain mineral homeostasis ● Rickets
● In balances of this hormones causes bonde disorder ○ the same as osteomalacia, but it occurs in the growing skeleton
■ For pediatric form of vitamin D deficiency
■ Affects the size of the bone and the heigh that's why it should be
diagnose as early as possible
● Osteoporosis

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 ○ Abnormal loss of bone with increased risk of fractures, spinal deformities, and
loss of stature
■ Ex: normally 5’6 ka then eventually nagging 5’4 ka dahil nagiging kuba
ka
■ Osteoporosis is associated with osteopenia → there is reduction in the
mineral content of the bone (bone loss)
● Yung bones parang sponge na may mga butas butas
● If there is bone loss there is an:
○ Increase in degradation
○ Decrease bone formation
● Paget’s Disease
○ unknown origin, characterized by excessive bone destruction and disorganized
repair
■ Idiopathic in nature: unknown origin
■ Fast turnover of old bones to newborns
■ Fragile, misshapen, and brittle
● Disorganized repair: Misshapen of pelvis, skull, spine and
legs (abnormal stature)
○ Complications: skeletal deformity, musculoskeletal pain, kidney stones, and
organ dysfunction secondary to pressure from bony overgrowth
Drugs Associated with Bone Loss/Fracture
Terms to Remember
● Osteoblasts
○ bone cells that promote bone formation
○ B: Building → formation of new bones
○ Helped by Vitamin A → promotes bone formation
● Osteoclasts
○ bone cells that promotes bone resorption
■ withdraw : since demineralization which releases minerals from the
bones to the blood
○ Degrade bone to initiate normal bone remodeling
○ C: Crush, recycle ( → degrading)
● Bone remodeling
○ to remove and replace damaged bone and to maintain calcium homeostasis
■ Happens throughout life
■ Every year, 10% of bones are being remodels since our body has to
adjust to certain mechanical changes
■ To adjust our body’s structure to meet the mechanical needs such as
walking, running or any type of movements
■ To remodel stronger bones
■ Important for repairing of bones due to fractures
■ Prevent accumulation of old bones
■ Plays an important role in calcium homeostasis
● Bone mineralization
○ Hydroxyapatite (calcium phosphate) deposited in bone matrix → increases bone
strength
○ Responsible for bones strength (increase bone mass and density)
● Bone Loss
○ bone resorption exceeds bone formation
○ NO new bones or healthy bones
○ Case in osteoporosis and partially to pagets’ disease
● Bone Resorption
○ release of minerals, decrease in bone mass and bone density
○ Withdraw: releases minerals from the bones to the blood
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 Drugs Used in Bone Disorders ● Excess Vitamin D → hypercalcemia → Kidney stones →
● Anti-resorptive drugs renal failure
○ Decrease bone loss ● Active Metabolites
■ Prevents osteoclast ○ liver: 25-hydroxyvitamin D or calcifediol)
○ kidney (1,25- dihydroxyvitamin D or calcitriol
○ bisphosphonates, calcitonin, selective estrogen receptor modulators (SERMs),
● Preparations
calcium ○ Ergocalciferol, Alfacalcidol and Calcitriol
● Anabolic agents
○ Increase bone formation
■ Promotes osteoblast
○ PTH, teriparatide
● Vitamin D preparations
○ Supplement vitamin D deficiency
○ Important in the role of absorption for calcium in the GIT (?)
● for nutritionally induced deficiency in bone mass

A. Parathyroid Hormone Actions of PTH and active vitamin D metabolites on intestine kidney, and bone
● PTH 84-amino-acid peptide
● acts on membrane G protein-coupled receptors ➡ increase cAMP in bone and renal Organ PTH Active Vitamin D metabolites
tubular cells
○ Note: Affects kidneys (renal tubular cells) and bones Intestine Indirectly increases calcium and Increases calcium and phosphate
● Note: decrease Ca → detected by parathyroid gland → releases PTH → increase cAMP phosphate absorption by increasing absorption
→ affects kidneys and bones vitamin D metabolites

● Teriparatide Kidney Decrease calcium excretion, Increases reabsorption of calcium and

○ An anabolic agent used for opsteptosis increases phosphate excretion
○ recombinant PTH
○ increases bone mass with less effect on plasma calcium
○ stimulating new bone formation by increasing osteoblasts
Bone Calcium and phosphate reabsorption
increases by continuous high
concentration. Low intermittent doses
increase bone formation
phosphate but usually net increase in
urinary calcium due to effects in GI tract
and bone.
Direct effect is increase calcium and
phospajhte resorption, indirect effects is
promoting mineralization by increasing
the availability of calcium and phosphate

Net effect on a Serum calcium increase, serum Serum Calcium and phosphate both
serum levels phosphate decrease increased.

C. Calcitonin
B. Vitamin D
● peptide hormone secreted by the thyroid gland
● synthesized in the skin from 7-dehydrocholesterol under the influence of UV light
● inhibiting bone resorption and renal excretion
○ natural form (vitamin D3, cholecalciferol)
○ too much calcium in blood → detected by parafollicular cells of thyroid gland →
○ plant form (vitamin D2, ergocalciferol)
release calcitonin → inhibition of osteoclast activity → no bone loss → improve
○ Excess vitamin D → increase calcium absorption in the GIT going to the blood.
bone mass
■ Hypervitaminosis → excessive dose of vitamins
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● Under antiresorptive drugs → prevent osteoclast
● for Paget’s disease ENDOCRINE PHARMACOLOGY (PART 7)
○ approved for treatment of osteoporosis
○ shown to increase bone mass and to reduce spine fractures
● Salcatonin (Salmon calcitonin) NORMAL GLUCOSE REGULATION
○ longer half-life, greater potency
○ administered by injection or as a nasal spray
● Insulin ● Counterregulatory Hormones
○ Calcitonin Has to be in synthetic form → greater half is seen in salcatonin
● cellular glucose uptake ● ⬆ blood glucose (BG)
D. Estrogens ● glucose ➡ energy ● Glucagon
● Role in bone integrity ● AA incorporation of proteins ● Growth hormone
● increase osteoblast proliferation, inhibits osteoclast precursors ● ⬇ glucose from liver, muscle ● Catecholamines
● augment the production of TGF-β and bone morphogenic proteins, and inhibit apoptosis ● glycogen, or AA ● Cortisol
(cell death) ● ⬇ FA breakdown to ketone bodies
○ Inhibits apoptosis because we want bone formation
● TGF-β: stimulates matrix protein synthesis ● Incretin Hormones ➔ Amylin
○ Also known as the transforming growth factor - beta. ● gastric inhibitory peptide (GIP) ➔ T1DM: little to none
○ Help estrogen as to the osteoclast formation inhibition. ● glucagon-like peptide-1 (GLP-1) in ➔ T2DM: insufficient
● Bone morphogenic proteins (BMP) : under the family of TGF-B → important in ● response to glucose ingestion ➔ ⬆ GET
stimulating growth factors → important in cell differentiation → production of osteoblast ● ⬆ glucose-dependent insulin ➔ ⬇ glucagon
E. Bisphosphonates secretion ➔ appetite suppression
● Alendronate, Etidronate, Ibandronate, Pamidronate, Risedronate, Tiludronate, and ● ⬇ glucagon secretion
Zoledronic acid ● ⬇ GET
● Mechanism of Action: ● ⬆ β-cell growth/replication
○ ⬇ osteoclastic bone resorption → increase bone mass, lessen bone loss ● appetite suppression
○ ⬆ osteoclast apoptosis ⬇ cholesterol pathway
● increase bone mass, ⬇ risk of fracture
● ✅ osteoporosis and Paget’s disease
F. Fluoride DIABETES MELLITUS
● large enough doses, fluoride stimulates bone formation by osteoblastic stimulation ➔ a group of metabolic diseases characterized by inappropriate hyperglycemia resulting from
● increases bone formation earlier defects in insulin secretion, insulin action, or both
● increases spinal bone density
● therapeutic doses: ≥ 10 mg/day ➔ Acute Hyperglycemia
● ***Limited epidemiological/clinical evidence ◆ polyuria, polydipsia, polyphagia, weight loss, blurred vision,
● Not DOC due to its large dose, limited source of fluoride, undesired taste, less clinical fatigue, headache, and poor wound healing
evidence.
➔ Chronic hyperglycemia
G. Calcimimetics
◆ damage and potentially failure of various organs, including the
● Cinacalcet
● enhance the sensitivity of the parathyroid Ca2+-sensing receptor to the concentration of eyes, heart, kidneys, blood vessels, and nerves
blood Ca2+
● Effects: decrease PTH secretion, reduce blood calcium
● treat secondary hyperparathyroidism in chronic kidney disease and hypercalcemia in
parathyroid carcinoma.
○ Hyperparathyroidism → High PTH and High Calcium
■ Calcinemtic reduces PTH and calcium

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