Premarin) are used for hormone replacement therapy (HRT) • synthetic estrogens with high

bioavailability (ethinyl estradiol, mestranol) are used as hormonal contraceptives MECHANISM OF

ACTION • Activates estrogen receptors; leads to changes in rates of transcription of estrogen-
regulated genes SIDE EFFECTS • Breakthrough bleeding, Nausea, Breast tenderness • Migraine,
Thromboembolism (DVTs), • Gallbladder disease • Hypertriglyceridemia, Hypertension, • Premature
closure of the epiphysis in young females, • Increased risk of breast and endometrial cancer
(remedy: add progesterone to the preparation) ESTROGEN Ethinyl Estradiol [X], Mestranol [X],
Estradiol Cypionate, Premarin, Estriol Uses Primary hypogonadism, Postmenopausal hormonal
replacement therapy, Osteoporosis, Contraception, Intractable dysmenorrhea “PREMARIN is from
PREgnant MARe’s urine” • Ethinyl Estradiol PO/TD/IM/Intravaginal Notes has low • Estradiol
cypionate is IM with longer t½ • Additive hypokalemia with loop diuretics and thiazides
bioavailability • Premarin is a mixture of conjugated estrogen used in HRT • Effects of Estrogen:
growth of genital structures and • Deoxycorticosterone is the precursor of aldosterone Notes •
Fludrocortisone also has significant glucocorticoid activity • Also, with weak antagonist effect at the
androgen receptor • Aldosterone is implicated in myocardial and vascular fibrosis and baroreceptor
dysfunction GONADAL HORMONES AND INHIBITORS Katzung and Trevor’s Pharmacology
Examination and Board Review. 12th ed. 2018 SYNTHETIC ESTROGEN Diethylstilbestrol (DES) [X] Uses
Atrophic vaginitis, Hormone replacement therapy, Prevention of adverse pregnancy outcomes,
Metastatic prostate cancer Notes Associated with Infertility, Ectopic pregnancy Clear cell vaginal
adenocarcinoma in daughters of mothers who took DES PROGESTINS Norgestrel [X], Norethindrone,
Ethynodiol, Megestrol, Desogestrel, Norelgestromin, Norgestimate, Etonogestrel, Progesterone,
Levonorgestrel, Dydrogesterone, Ulipristal, Tibolone, Norethisterone, Dienogest MOA Activates
progesterone receptors; Changes rates of Uses transcription of progesterone-regulated genes
Hormone replacement therapy (given together with Estrogen, to prevent estrogen-induced
endometrial cancer), contraception, assisted reproduction (for maintenance of pregnancy),
anovulation induction (given in high doses to suppress FSH and LH) TOPNOTCH MEDICAL BOARD
PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY MARIA YNA PEREYRYA-BORLONGAN, MD-MBA
Page 63 of 95 For inquiries visit www.topnotchboardprep.com.ph or
https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for the October
2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts
regularly. SE TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN HANDOUT BY DR. YNS
PEREYRA-BORLONGAN, MD-MBA For inquiries visit www.topnotchboardprep.com.ph or
https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for October 2022
PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
Hypertension, Decreased HDL, Weight gain, Reversible decrease in bone mineral density, Delayed
resumption of ovulation after use • Prevents estrogen-induced endometrial cancer when used in
combination • Megestrol is used as an appetite stimulant • Medroxyprogesterone has a better oral
bioavailability Notes • L-Norgestrel and Norethindrone has more androgenic effect • Effects of
progesterone: induces secretory changes in the endometrium, stabilize the endometrium, affect
carbohydrate metabolism and stimulate deposition of fat, high doses suppress FSH and LH secretion
TIBOLONE is a synthetic steroid with weak estrogenic, progestogenic and androgenic activity, and
hence is an agonist of the estrogen, progesterone and androgen receptor. It is primarily used in
menopausal hormone therapy, postmenopausal osteoporosis and endometriosis. Oral
Contraceptives: Contraindications and Disease Risk Contraindications Absolute • Women age >35
years who smoke > 15 cigarettes per day • Known ischemic heart disease or multiple risk factors for
cardiovascular disease (older age, smoking, diabetes, and hypertension) • Past thromboembolic
event, stroke or known thrombogenic mutations • Complicated valvular heart disease • Complicated
solid organ transplantation • Hypertension (systolic >160 mmHg or diastolic >100 mmHg) • Systemic
lupus erythematous (positive or unknown antiphospholipid antibodies • Cirrhosis, hepatic adenoma
or hepatoma • Pregnancy and early postpartum (35; no relation to progestin type • Hypertension-
relative risk 1.8 (current users) and 1.2 (previous users) • Venous thrombosis relative risk ~4; may be
higher with third generation progestin, drospirenone, and patch; compounded by obesity (tenfold
increased risk compared with nonobese, no OCP); markedly increased with factor V Leiden or
prothrombin gene mutations • Stroke—slight increase; unclear relation to migraine headache •
Cerebral vein thrombosis-relative risk ~13-15; synergistic with prothrombin gene mutation • Cervical
cancer—relative risk 2—4 • Breast cancer—may increase risk, particularly in carriers of BRCA1 and
possibly BRCA2 Decreased Ovarian cancer—50% reduction in risk Endometrial cancer—40%
reduction in risk CONTRACEPTIVES *Do not protect against STIs CONTRACEPTIVES HORMONAL
CONTRACEPTIVES • contain either a combination of an estrogen and a progestin or a progestin alone
• available in a variety of preparations o oral pills o long-acting injections (good for 3 months) o
implants (good for 3 years) o transdermal patches o vaginal rings o intrauterine devices (IUDs) MOA
of Combination Hormonal Contraceptives • inhibition of ovulation (the primary action) • effects on
the cervical mucus glands, uterine tubes, and endometrium that decrease the likelihood of
fertilization and implantation Types of Oral Contraceptives • MONOPHASIC o combination estrogen-
progestin tablets that are taken in constant dosage throughout the menstrual cycle • BIPHASIC or
TRIPHASIC o combination preparations in which the progestin or estrogen dosage, or both, changes
during the month o more closely mimics hormonal changes in menstrual cycle • PROGESTIN-ONLY
PREPARATIONS o recommended for breastfeeding moms since they do not affect lactation Postcoital
Contraceptives/ Emergency Contraception • prevent pregnancy if administered within 72 h after
unprotected intercourse • progestin (L-Norgestrel) alone, estrogen alone, combination of estrogen
and progestin o progestin-only preparation causes fewer side effects than the estrogen-containing
preparations COMBINED ORAL CONTRACEPTIVE ESTRADIOL + NORETHINDRONE [X] ETHINYL
ESTRADIOL + DESOGESTREL/NORGESTREL ETHINYL ESTRADIOL + DROSPIRENONE ETHINYL
ESTRADIOL + NORGESTIMATE ETHINYL ESTRADIOL + NORETHISTERONE MOA Combined oral
contraceptive, activates estrogen and progesterone receptors, inhibits ovulation, effects on cervical
mucus gland, uterine tubes and endometrium lead to decreased fertility, inhibit ovulation when
given before the LH surge Uses Contraception, Hypogonadism, Acne, Hirsutism, Dysmenorrhea,
Endometriosis SE Breakthrough bleeding, Nausea, Breast tenderness, Skin pigmentation,
Thromboembolism (DVTs), Breast cancer (earlier onset), headache, skin pigmentation, depression,
weight gain and hirsutism for older OCPs OCPs: increase HYPERCOAGUABILITY Breakthrough
bleeding – bleeding in between dosages of OCPs Notes • Lifetime risk of breast cancer is NOT
changed • Combined OCPs may be used for androgen-induced hirsutism PROGESTIN-ONLY
CONTRACEPTIVE MEDROXY-PROGESTERONE ACETATE [D] MOA Activates progesterone receptors.
Prevents conception by altering cervical mucus and creating a hostile endometrium Uses SE
Contraception, Hormone replacement therapy Breakthrough bleeding, Hair loss, Dysmenorrhea,
Delayed return of fertility, Osteoporosis Notes • Intramuscular depot preparation (Depo-Provera)
POSTCOITAL CONTRACEPTIVE LEVONORGESTREL, ETHINYL ESTRADIOL + LEVONORGESTREL MOA
Activates estrogen and/or progesterone receptors. Thickens cervical mucus. Inhibits ovulation. Uses
Emergency contraception SE Severe nausea, vomiting, Breast tenderness, Irregular Bleeding,
Headache, Dizziness (fewer SE compared to estrogen alone and combination contraceptives) Notes
Must be taken within 72 hours of unprotected sexual intercourse (not effective once implantation
has occurred) SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) • mixed estrogen agonists
that have estrogen agonist effects in some tissues and act as partial agonists or antagonists in other
tissues TAMOXIFEN [D], TOREMIFENE [D] MOA Estrogen antagonist actions in breast tissue and CNS.
Estrogen agonist effects in uterus, liver and bone. Uses Hormone-responsive breast cancer,
prophylaxis of breast CA esp. in those with high risk Given for breast cancer patients who are ER+
PR+ SE Hot flushes, Thromboembolism (DVTs), Endometrial hyperplasia, Endometrial cancer •
Prevents osteoporosis in post-menopausal women and decreases risk of atherosclerosis at the risk of
causing endometrial cancer Notes FLUVESTRANT is a FULL ESTROGEN RECEPTOR ANTAGONIST (No
agonist effect) for hormone receptor positive metastatic breast cancer resistance to Tamoxifen
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY MARIA YNA
PEREYRYA-BORLONGAN, MD-MBA Page 64 of 95 For inquiries visit www.topnotchboardprep.com.ph
or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for the
October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our
handouts regularly. TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN HANDOUT BY DR. YNS
PEREYRA-BORLONGAN, MD-MBA For inquiries visit www.topnotchboardprep.com.ph or
https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for October 2022
PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY MARIA YNA
PEREYRYA-BORLONGAN, MD-MBA Page 65 of 95 For inquiries visit www.topnotchboardprep.com.ph
or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for the
October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our
handouts regularly. RALOXIFENE [X] MOA Estrogen antagonist actions in breast tissue, uterus and
CNS. Estrogen agonist effects in liver and bone. Increases bone mineral density. Uses Osteoporosis,
Breast cancer prevention Preferred in patient with history of breast cancer in the management of hot
flushes. SE Hot flushes, Thromboembolism (DVTs) Notes • Reduces incidence of breast cancer in
women who are at very high risk • No estrogenic effects on endometrial tissue Note the difference in
the MOA of Tamoxifen and Raloxifene (location). Also appreciate the difference in usage of tamoxifen
as an agonist and antagonist Dr. Rodriguez CLOMIPHENE [X] MOA Partial agonist of estrogen
receptors in pituitary. Reduces negative feedback by estradiol. Increases FSH and LH output. Uses
Induction of ovulation for women who want to get pregnant Acts as antagonist to estrogen receptors
in the pituitary → inhibit negative feedback mechanism by estrogen → leads to pituitary stimulation
causing ↑ LH and FSH SE Hot flushes, Eye symptoms (afterimages), Headache, Constipation,
Reversible hair loss, Ovarian enlargement, Multiple pregnancies (10%) Notes Increased risk of low-
grade ovarian cancer with long term use MISCELLANEOUS ESTROGEN ANTAGONISTS AROMATASE
INHIBITOR ANASTROZOLE [X], LETROZOLE, EXEMESTANE MOA Reduces estrogen synthesis by
inhibiting aromatase Aromatase is the enzyme which converts Testosterone to Estrogen(Estradiol)
Uses Breast cancer, Precocious puberty SE Hot flushes, Musculoskeletal disorders, Osteoporosis, Joint
pains Notes • Effective against breast cancers that have become resistant to tamoxifen Exemestane is
an IRREVERSIBLE inhibitor OVARIAN INHIBITOR (ANTI-ANDROGEN) DANAZOL [X] MOA Weak
cytochrome P450 inhibitor and partial agonist of progestin and androgen receptors Uses
Endometriosis, Fibrocystic disease, Hemophilia, Angioneurotic edema SE Acne, Hirsutism, Weight
gain, Menstrual disturbances, Hepatic dysfunction Notes • Contraindicated during pregnancy and
breast-feeding May also act on Glucocorticoid receptors GNRH AGONISTS LEUPROLIDE,
GONADORELIN [B], GOSERELIN, HISTRELIN, NAFARELIN, TRIPTORELIN All are Preg Cat X except
Gonadorelin MOA Agonist of GnRH receptors. Increased LH and FSH secretion with INTERMITTENT
administration. Reduced LH and FSH secretion with PROLONGED CONTINUOUS administration (due
to downregulation of GnRH receptors in the pituitary cells that normally release LH and FSH) Uses
Ovarian Suppression, Controlled ovarian hyperstimulation, Endometriosis, Myoma uteri, Central
Precocious puberty, Advanced Prostate cancer SE Hot flushes, Sweats, Headache, Light-headedness,
Injection site reactions, Nausea, Osteoporosis, Gynecomastia, Reduced libido, Decreased hematocrit
Notes • Symptoms of hypogonadism with continuous treatment Temporary exacerbation of
precocious puberty or prostate cancer, Apoplexy and Blindness during the first few weeks of therapy
(remedy: co-administer Flutamide, an androgen receptor antagonist) GNRH ANTAGONISTS Ganirelix
[X], Cetrorelix, Abarelix, Degarelix MOA Agonist of GnRH receptors. Increased LH and FSH secretion
with INTERMITTENT administration. Reduced LH and FSH secretion with PROLONGED CONTINUOUS
administration (due to downregulation of GnRH receptors in the pituitary cells that normally release
LH and FSH) Uses Ovarian Suppression, Controlled ovarian hyperstimulation, Endometriosis, Myoma
uteri, Central Precocious puberty, Advanced Prostate cancer SE Hot flushes, Sweats, Headache, Light-
headedness, Injection site reactions, Nausea, Osteoporosis, Gynecomastia, Reduced libido,
Decreased hematocrit Notes • Symptoms of hypogonadism with continuous treatment Temporary
exacerbation of precocious puberty or prostate cancer, Apoplexy and Blindness during the first few
weeks of therapy (remedy: co-administer Flutamide, an androgen receptor antagonist)
GLUCOCORTICOID AND PROGESTERONE RECEPTOR ANTAGONIST MIFEPRISTONE (RU-486) [X] MOA
Pharmacologic antagonist of glucoco